Glasdegib 100mg tablets
Prescription only
Requires a prescription from a doctor or prescriber
Tablet
100mg
Oral
Glasdegib, also known as PF-04449913, is a small-molecule hedgehog signaling inhibitor selected under the group of benzimidazoles.
Active ingredients:
Glasdegib
1 safety notice
Safety information for pregnancy and breastfeeding
Pregnancy
Based on its mechanism of action and findings in animal embryo-fetal developmental toxicity studies, glasdegib can cause fetal harm when administered to a pregnant woman.
There are no clinical data on the use of glasdegib in pregnant women to inform of a drug-associated risk of major birth defects and miscarriage.
Glasdegib is not recommended for use during pregnancy.
Conduct pregnancy testing in female patients of reproductive potential prior to initiating treatment with glasdegib.
Report pregnancy exposures to Pfizer at 1-800-438-1985.[L45728]
In animal embryo-fetal developmental toxicity studies, repeat-dose oral administration of glasdegib during organogenesis at maternal exposures that were less than the human exposure at the recommended dose resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits.
In animal embryo-fetal developmental toxicity studies, repeat-dose oral administration of glasdegib during organogenesis at maternal exposures that were less than the human exposure at the recommended dose resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits.
Always consult your doctor or midwife before taking any medicine during pregnancy or while breastfeeding. Source: DrugBank (CC BY-NC 4.0).
Official documents, adverse reaction reporting, and safety monitoring
Report a side effect
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Official medicine documents
Source: MHRA Products DatabaseOGL 3.0
Updated 3 months ago(16 Jan 2026)Safety monitoring data
Yellow Card reports
MHRA
The MHRA Yellow Card scheme collects reports of suspected side effects from healthcare professionals and patients. View the Drug Analysis Profile (iDAP) for real-world adverse reaction data.
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Suspected adverse reactions reported for Glasdegib
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Submit a Yellow Card report to the MHRA
Data from the MHRA Yellow Card scheme. A reported reaction does not necessarily mean the medicine caused it. Contains public sector information licensed under the Open Government Licence v3.0.
EudraVigilance
EMA
The European Medicines Agency (EMA) collects suspected adverse reaction reports from across the EU/EEA through the EudraVigilance system. Search for safety data on this medicine.
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Suspected adverse reactions reported for Glasdegib
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EudraVigilance data is published by the European Medicines Agency (EMA). A suspected adverse reaction is not necessarily caused by the medicine.
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Daurismo 100mg tablets
Therapeutically similar medicines
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Similarity based on WHO Anatomical Therapeutic Chemical (ATC) classification and NHS BNF section grouping. Source data: NHS dm+d via TRUD (OGL v3.0), WHO ATC/DDD Index.
Clinical guidelines and formulary information
British National Formulary
Glasdegib
BNF
Drug monograph — bnf.nice.org.ukSource: British National Formulary, NICE. Joint Formulary Committee. Contains public sector information licensed under the Open Government Licence v3.0.
NICE clinical guidance(1)
Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
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Supply & product information
Official product databases and supply status monitoring
Pharmacy links redirect to the retailer's own search and do not represent real-time stock levels. emc (electronic medicines compendium) is operated by Datapharm Ltd. Shortage information sourced from NHS Specialist Pharmacy Service (SPS), sps.nhs.uk.
Codes for healthcare professionals and prescribing systems
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These codes are used by healthcare IT systems and prescribers to identify this medicine.
NHS UK identifiers
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SNOMED CT and dm+d codes from NHS TRUD (Technology Reference data Update Distribution), licensed under the Open Government Licence v3.0. BNF codes from NHS Business Services Authority (NHSBSA). ATC codes from the WHO Collaborating Centre for Drug Statistics Methodology (whocc.no).
Active and completed clinical studies from ClinicalTrials.gov
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Searching UK clinical trials...
Source: ClinicalTrials.gov, a database of the U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Data accessed via ClinicalTrials.gov API v2. Trial information is provided for research purposes and does not constitute medical advice.
Pharmacology and chemical data from DrugBank
Key facts
Drug status
Approved
Major interactions
None known
Half-life
17.4 hours
Mechanism
Glasdegib is a potent and selective inhibitor of the hedgehog signaling pathway…
Food interactions
3 warnings
Human targets
2 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
50 mg
Glasdegib presents a dose-proportional pharmacokinetic profile which is observed by the presence of a broad dose-proportional maximum plasma concentration.…
Half-life
17.4 hours
The reported half-life of glasdegib is of 17.4 hours.T367
Protein binding
91%
Glasdegib is reported to be 91% protein bounded which is explained due to its high lipophilic profile.T367
Volume of distribution
50 mg
Glasdegib reported volume of distribution in a dose of 50 mg is 225 L.
[A173857]…
[A173857]…
Metabolism
69%
After oral administration, glasdegib was primarily metabolized by CYP3A4 with minor contributions of CYP2C8 and UGT1A9.…
Elimination
100 mg
From a single oral dose of 100 mg radiolabeled glasdegib, 49% is eliminated in the urine from which 17% is excreted as the unchanged form while…
Clearance
50 mg
The clearance rate of 50 mg of glasdegib is reported to be of 5.22…
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Status:
Approved
Investigational
Small molecule
About this compound
Glasdegib, also known as PF-04449913, is a small-molecule hedgehog signaling inhibitor selected under the group of benzimidazoles. In early research, benzimidazoles attracted large interest as they represented a class of inhibitors with low molecular weight, potent inhibitory activity, and lacking unstable functionality.[A40310] The great lipophilicity of this group of compounds brought interest to further modification. This analysis concluded that the presence of p-cyano ureas presented good physicochemical and pharmacokinetic properties from which glasdegib was developed.[A40310]
Glasdegib was developed by Pfizer Inc and approved on November 21, 2018 by the FDA for the treatment of Acute Myeloid Leukemia (AML).[L11935] Glasdegib targets cancerous cells by inhibiting the sonic hedgehog receptor smoothened (SMO), a transmembrane protein involved in the Hedgehog (Hh) signaling cascade.[A258493] Aberrant of Hh signaling is one of the main pathophysiologies of AML, with observed overexpression or constitutive activation of SMO.[A258498][A258503] Although the efficacy of glasdegib monotherapy is limited, the landmark Phase 2 Bright AML 1003 trial showed a superior overall survival and complete response when glasdegib is combined with low dose cytarabine. Currently, the current gold standard of AML in older patients is still venetoclax with hypomethylation agents, new clinical combinations of glasdegib are being tested in hope of replacing venetoclax due to glasdegib's more favorable side effects profile.[A258493]
Glasdegib was developed by Pfizer Inc and approved on November 21, 2018 by the FDA for the treatment of Acute Myeloid Leukemia (AML).[L11935] Glasdegib targets cancerous cells by inhibiting the sonic hedgehog receptor smoothened (SMO), a transmembrane protein involved in the Hedgehog (Hh) signaling cascade.[A258493] Aberrant of Hh signaling is one of the main pathophysiologies of AML, with observed overexpression or constitutive activation of SMO.[A258498][A258503] Although the efficacy of glasdegib monotherapy is limited, the landmark Phase 2 Bright AML 1003 trial showed a superior overall survival and complete response when glasdegib is combined with low dose cytarabine. Currently, the current gold standard of AML in older patients is still venetoclax with hypomethylation agents, new clinical combinations of glasdegib are being tested in hope of replacing venetoclax due to glasdegib's more favorable side effects profile.[A258493]
Properties:
View FDA drug labelsolid
Avg. mass: 374.45 Da
DrugBank indication
Glasdegib, in combination with cytarabine, is indicated for the treatment of newly diagnosed acute myeloid leukemia in adult patients who are over 75 years old or that have co-morbidities that preclude intensive induction chemotherapy.
[L5080]
Acute myeloid leukemia is characterized by abnormal production of myeloblasts, red cells, or platelets. It is considered a cancer of blood and bone marrow and it is the most common type of acute leukemia in adults.
[L4832]
[L5080]
Acute myeloid leukemia is characterized by abnormal production of myeloblasts, red cells, or platelets. It is considered a cancer of blood and bone marrow and it is the most common type of acute leukemia in adults.
[L4832]
Also known as(86)
Glasdegib
Protein Gx
SMOH
2.7.11.1
FK506-binding protein 12-rapamycin complex-associated protein 1
FKBP12-rapamycin complex-associated protein
FRAP
FRAP1
Dosage forms(6)
Tablet (Oral) — 100 mg
Tablet (Oral) — 25 mg
Tablet, film coated (Oral) — 100 mg/1
Tablet, film coated (Oral) — 100 MG
Tablet, film coated (Oral) — 25 mg/1
Tablet, film coated (Oral) — 25 MG
Molecular properties(19)
Drug interactions(875)
Known interactions with other medications. Always consult a healthcare professional.
The serum concentration of Afatinib can be increased when it is combined with Glasdegib.
The serum concentration of Bosutinib can be increased when it is combined with Glasdegib.
Brentuximab vedotin
Unknown severity
The serum concentration of Brentuximab vedotin can be increased when it is combined with Glasdegib.
Colchicine
Unknown severity
The serum concentration of Colchicine can be increased when it is combined with Glasdegib.
The serum concentration of Edoxaban can be increased when it is combined with Glasdegib.
Ledipasvir
Unknown severity
The serum concentration of Ledipasvir can be increased when it is combined with Glasdegib.
The serum concentration of Naloxegol can be increased when it is combined with Glasdegib.
The serum concentration of Pazopanib can be increased when it is combined with Glasdegib.
Prucalopride
Unknown severity
The serum concentration of Prucalopride can be increased when it is combined with Glasdegib.
Ranolazine
Unknown severity
The serum concentration of Ranolazine can be increased when it is combined with Glasdegib.
The excretion of Silodosin can be decreased when combined with Glasdegib.
The serum concentration of Topotecan can be increased when it is combined with Glasdegib.
Everolimus
Unknown severity
The serum concentration of Everolimus can be increased when it is combined with Glasdegib.
The serum concentration of Rifaximin can be increased when it is combined with Glasdegib.
Mifepristone
Unknown severity
The serum concentration of Glasdegib can be increased when it is combined with Mifepristone.
Vincristine
Unknown severity
The excretion of Vincristine can be decreased when combined with Glasdegib.
Doxorubicin
Unknown severity
The serum concentration of Doxorubicin can be increased when it is combined with Glasdegib.
Lumacaftor
Unknown severity
The serum concentration of Glasdegib can be decreased when it is combined with Lumacaftor.
Leuprolide
Unknown severity
The risk or severity of QTc prolongation can be increased when Leuprolide is combined with Glasdegib.
The risk or severity of QTc prolongation can be increased when Goserelin is combined with Glasdegib.
Erythromycin
Unknown severity
The risk or severity of QTc prolongation can be increased when Erythromycin is combined with Glasdegib.
Azithromycin
Unknown severity
The risk or severity of QTc prolongation can be increased when Azithromycin is combined with Glasdegib.
Moxifloxacin
Unknown severity
The risk or severity of QTc prolongation can be increased when Moxifloxacin is combined with Glasdegib.
Sulfisoxazole
Unknown severity
The risk or severity of QTc prolongation can be increased when Sulfisoxazole is combined with Glasdegib.
The risk or severity of QTc prolongation can be increased when Methadone is combined with Glasdegib.
The risk or severity of QTc prolongation can be increased when Diltiazem is combined with Glasdegib.
The risk or severity of QTc prolongation can be increased when Glasdegib is combined with Clozapine.
The risk or severity of QTc prolongation can be increased when Sulpiride is combined with Glasdegib.
Nimodipine
Unknown severity
The risk or severity of QTc prolongation can be increased when Nimodipine is combined with Glasdegib.
The risk or severity of QTc prolongation can be increased when Promazine is combined with Glasdegib.
Prochlorperazine
Unknown severity
The risk or severity of QTc prolongation can be increased when Prochlorperazine is combined with Glasdegib.
Droperidol
Unknown severity
The risk or severity of QTc prolongation can be increased when Droperidol is combined with Glasdegib.
Chlorpromazine
Unknown severity
The risk or severity of QTc prolongation can be increased when Chlorpromazine is combined with Glasdegib.
Oxaliplatin
Unknown severity
The risk or severity of QTc prolongation can be increased when Oxaliplatin is combined with Glasdegib.
Ciprofloxacin
Unknown severity
The risk or severity of QTc prolongation can be increased when Ciprofloxacin is combined with Glasdegib.
Perflutren
Unknown severity
The risk or severity of QTc prolongation can be increased when Perflutren is combined with Glasdegib.
Cinnarizine
Unknown severity
The risk or severity of QTc prolongation can be increased when Cinnarizine is combined with Glasdegib.
The risk or severity of QTc prolongation can be increased when Atropine is combined with Glasdegib.
Chloroquine
Unknown severity
The risk or severity of QTc prolongation can be increased when Chloroquine is combined with Glasdegib.
The risk or severity of QTc prolongation can be increased when Adenosine is combined with Glasdegib.
Pentamidine
Unknown severity
The risk or severity of QTc prolongation can be increased when Pentamidine is combined with Glasdegib.
Gadobenic acid
Unknown severity
The risk or severity of QTc prolongation can be increased when Gadobenic acid is combined with Glasdegib.
Carbinoxamine
Unknown severity
The risk or severity of QTc prolongation can be increased when Carbinoxamine is combined with Glasdegib.
Dolasetron
Unknown severity
The risk or severity of QTc prolongation can be increased when Dolasetron is combined with Glasdegib.
Roxithromycin
Unknown severity
The risk or severity of QTc prolongation can be increased when Roxithromycin is combined with Glasdegib.
Nalidixic acid
Unknown severity
The risk or severity of QTc prolongation can be increased when Nalidixic acid is combined with Glasdegib.
The risk or severity of QTc prolongation can be increased when Cinoxacin is combined with Glasdegib.
Granisetron
Unknown severity
The risk or severity of QTc prolongation can be increased when Granisetron is combined with Glasdegib.
Ondansetron
Unknown severity
The risk or severity of QTc prolongation can be increased when Ondansetron is combined with Glasdegib.
Levosimendan
Unknown severity
The risk or severity of QTc prolongation can be increased when Levosimendan is combined with Glasdegib.
Showing 50 of 875 interactions
Food & lifestyle interactions
Advice
Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of glasdegib.
Advice
Take at the same time every day.
Advice
Take with or without food.
Toxicity & overdose
Based on its mechanism of action and findings in animal embryo-fetal developmental toxicity studies, glasdegib can cause fetal harm when administered to a pregnant woman. There are no clinical data on the use of glasdegib in pregnant women to inform of a drug-associated risk of major birth defects and miscarriage. Glasdegib is not recommended for use during pregnancy.
Conduct pregnancy testing in female patients of reproductive potential prior to initiating treatment with glasdegib. Report pregnancy exposures to Pfizer at 1-800-438-1985.
[L45728]
In animal embryo-fetal developmental toxicity studies, repeat-dose oral administration of glasdegib during organogenesis at maternal exposures that were less than the human exposure at the recommended dose resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits. Advise pregnant women of the potential risk to a fetus.
[L45728]
Carcinogenicity studies have not been performed with glasdegib.
Glasdegib was not mutagenic in vitro in the bacterial reverse mutation (Ames) assay and was not clastogenic in the in vitro chromosome aberration assay in human lymphocytes. Glasdegib was not clastogenic or aneugenic in the rat micronucleus assay.
[L45728]
Based on nonclinical safety findings, glasdegib has the potential to impair reproductive function in males. Men should seek advice on effective fertility preservation before treatment.
In repeat-dose toxicity studies in rats, findings observed in the male reproductive tract included adverse testicular changes with glasdegib at doses ≥50 mg/kg/day and consisted of minimal to severe hypospermatogenesis characterized by partial to complete loss of spermatogonia, spermatocytes and spermatids and testicular degeneration. Hypospermatogenesis did not recover whereas testicular degeneration did recover. The dose at which testicular effects were observed in male rats was identified as 50 mg/kg/day with corresponding systemic exposures that were approximately 6.6 times (based on AUC) those associated with the observed human exposure at the 100 mg once daily dose.
There is no specific antidote for DAURISMO.
Management of DAURISMO overdose should include symptomatic treatment and ECG monitoring. Glasdegib has been administered in clinical studies up to a dose of 640 mg/day. At the highest dosage, the adverse reactions that were dose-limiting were nausea, vomiting, dehydration, hypotension, fatigue, and dizziness.
[L45728]
Conduct pregnancy testing in female patients of reproductive potential prior to initiating treatment with glasdegib. Report pregnancy exposures to Pfizer at 1-800-438-1985.
[L45728]
In animal embryo-fetal developmental toxicity studies, repeat-dose oral administration of glasdegib during organogenesis at maternal exposures that were less than the human exposure at the recommended dose resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits. Advise pregnant women of the potential risk to a fetus.
[L45728]
Carcinogenicity studies have not been performed with glasdegib.
Glasdegib was not mutagenic in vitro in the bacterial reverse mutation (Ames) assay and was not clastogenic in the in vitro chromosome aberration assay in human lymphocytes. Glasdegib was not clastogenic or aneugenic in the rat micronucleus assay.
[L45728]
Based on nonclinical safety findings, glasdegib has the potential to impair reproductive function in males. Men should seek advice on effective fertility preservation before treatment.
In repeat-dose toxicity studies in rats, findings observed in the male reproductive tract included adverse testicular changes with glasdegib at doses ≥50 mg/kg/day and consisted of minimal to severe hypospermatogenesis characterized by partial to complete loss of spermatogonia, spermatocytes and spermatids and testicular degeneration. Hypospermatogenesis did not recover whereas testicular degeneration did recover. The dose at which testicular effects were observed in male rats was identified as 50 mg/kg/day with corresponding systemic exposures that were approximately 6.6 times (based on AUC) those associated with the observed human exposure at the 100 mg once daily dose.
There is no specific antidote for DAURISMO.
Management of DAURISMO overdose should include symptomatic treatment and ECG monitoring. Glasdegib has been administered in clinical studies up to a dose of 640 mg/day. At the highest dosage, the adverse reactions that were dose-limiting were nausea, vomiting, dehydration, hypotension, fatigue, and dizziness.
[L45728]
How it works
Mechanism of action
Glasdegib is a potent and selective inhibitor of the hedgehog signaling pathway that acts by binding to the smoothened (SMO) receptor.[A40310]
The hedgehog signaling pathway is involved in maintenance of neural and skin stem cells. In this pathway, the binding of specific ligands to the transmembrane receptor patched (PTCH1) allows the activation of the transcriptional regulators GL11, GL12 and modulation of the gene expression through SMO-mediated signaling. The aberrant activation of the hedgehog pathway is thought to be implicated in the pathogenesis of chronic myeloid leukemia, medulloblastoma and basal cell carcinoma due to the hyperproliferative state that a modification on this pathway will produce.[A173860]
The hedgehog signaling pathway is involved in maintenance of neural and skin stem cells. In this pathway, the binding of specific ligands to the transmembrane receptor patched (PTCH1) allows the activation of the transcriptional regulators GL11, GL12 and modulation of the gene expression through SMO-mediated signaling. The aberrant activation of the hedgehog pathway is thought to be implicated in the pathogenesis of chronic myeloid leukemia, medulloblastoma and basal cell carcinoma due to the hyperproliferative state that a modification on this pathway will produce.[A173860]
Pharmacodynamics
In preclinical studies, glasdegib achieved a significant reduction in leukemic stem cell burden in xenograft models and a reduction in cell population expressing leukemic stem cell markers.[A173857]
In clinical trials, glasdegib demonstrated a marked downregulation of more than 80% of the expression of glioma-associated transcriptional regulator GL11 in skin. In this same study 8% of the studied individuals with acute myeloid leukemia achieved morphological complete remission while 31% achieved stable disease state.[A173857]
The latest clinical trial proved glasdegib to generate an overall survival of 8.3 months which was almost double to what has been observed in patients under low-dose cytarabine treatment. As well, there have been reports of dose-dependent QTc prolongation in patients administered with glasdegib.[L5080]
In clinical trials, glasdegib demonstrated a marked downregulation of more than 80% of the expression of glioma-associated transcriptional regulator GL11 in skin. In this same study 8% of the studied individuals with acute myeloid leukemia achieved morphological complete remission while 31% achieved stable disease state.[A173857]
The latest clinical trial proved glasdegib to generate an overall survival of 8.3 months which was almost double to what has been observed in patients under low-dose cytarabine treatment. As well, there have been reports of dose-dependent QTc prolongation in patients administered with glasdegib.[L5080]
Pharmacokinetics
How the body processes this drug — absorption, distribution, metabolism, and elimination
Absorption
Glasdegib presents a dose-proportional pharmacokinetic profile which is observed by the presence of a broad dose-proportional maximum plasma concentration. In this study and on a dose of 50 mg, the median time to reach a maximum concentration of 321 ng/ml was of 4 hours with an AUC of 9587 ng.h/ml.
[A173857]
The oral bioavailability of glasdegib is reported to be of 55%.
[A40310]
In a multiple dose study of 50 mg, the Cmax, tmax and AUC was reported to be 542 ng/ml, 4 h and 9310 ng.h/ml respectively. In this same study, the average concentration at a steady state was of 388 ng/ml.
[A173857]
The absorption rates of glasdegib can be modified by the concomitant consumption of a high-fat, high-calorie meal.[FDA label]
[A173857]
The oral bioavailability of glasdegib is reported to be of 55%.
[A40310]
In a multiple dose study of 50 mg, the Cmax, tmax and AUC was reported to be 542 ng/ml, 4 h and 9310 ng.h/ml respectively. In this same study, the average concentration at a steady state was of 388 ng/ml.
[A173857]
The absorption rates of glasdegib can be modified by the concomitant consumption of a high-fat, high-calorie meal.[FDA label]
Half-life
The reported half-life of glasdegib is of 17.4 hours.T367
Protein binding
Glasdegib is reported to be 91% protein bounded which is explained due to its high lipophilic profile.T367
Volume of distribution
Glasdegib reported volume of distribution in a dose of 50 mg is 225 L.
[A173857]
The geometric mean (%CV) apparent volume of
distribution (Vz/F) was 188 L (20%) in patients with hematologic malignancies.
[L45728]
[A173857]
The geometric mean (%CV) apparent volume of
distribution (Vz/F) was 188 L (20%) in patients with hematologic malignancies.
[L45728]
Metabolism
After oral administration, glasdegib was primarily metabolized by CYP3A4 with minor contributions of CYP2C8 and UGT1A9. The amount of unchanged glasdegib in plasma accounts only for 69% of the administered dose.
[A173872]
[A173872]
Route of elimination
From a single oral dose of 100 mg radiolabeled glasdegib, 49% is eliminated in the urine from which 17% is excreted as the unchanged form while 42% is eliminated in feces where 20% represents the unchanged form.
[A173872][L45728]
[A173872][L45728]
Clearance
The clearance rate of 50 mg of glasdegib is reported to be of 5.22 L/h.
[A173857]
The geometric mean (%CV) apparent clearance of
6.45 L/h (25%) following 100 mg once daily dosing in patients with hematologic malignancies.
[L45728]
[A173857]
The geometric mean (%CV) apparent clearance of
6.45 L/h (25%) following 100 mg once daily dosing in patients with hematologic malignancies.
[L45728]
Drug targets(2)
Proteins and enzymes this drug interacts with in the body
Protein smoothened
SMO
inhibitor
Specific functioncAMP-dependent protein kinase inhibitor activity
Cellular location
Cell membrane
General function & pharmacology
G protein-coupled receptor which associates with the patched protein (PTCH) to transduce hedgehog protein signaling. Binding of sonic hedgehog (SHH) to its receptor patched prevents inhibition of smoothened (SMO) by patched. When active, SMO binds to and sequesters protein kinase A catalytic subunit PRKACA at the cell membrane, preventing PRKACA-mediated phosphorylation of GLI transcription factors which releases the GLI proteins from PRKACA-mediated inhibition and allows for transcriptional activation of hedgehog pathway target genes (By similarity).
Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia .
PMID:19592253
Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity)
Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia .
PMID:19592253
Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity)
Serine/threonine-protein kinase mTOR
MTOR
inhibitor
Specific functionATP binding
Cellular location
Lysosome membrane
General function & pharmacology
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals .
PMID:12087098 PMID:12150925 PMID:12150926 PMID:12231510 PMID:12718876 PMID:14651849 PMID:15268862 PMID:15467718 PMID:15545625 PMID:15718470 PMID:18497260 PMID:18762023 PMID:18925875 PMID:20516213 PMID:20537536 PMID:21659604 PMID:23429703 PMID:23429704 PMID:25799227 PMID:26018084 PMID:29150432 PMID:29236692 PMID:31112131 PMID:31601708 PMID:32561715 PMID:34519269 PMID:37751742
MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins .
PMID:15268862 PMID:15467718 PMID:17517883 PMID:18372248 PMID:18497260 PMID:18925875 PMID:20516213 PMID:21576368 PMID:21659604 PMID:23429704 PMID:30171069 PMID:29236692 PMID:37751742
Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) .
PMID:15268862 PMID:15467718 PMID:18497260 PMID:18925875 PMID:20516213 PMID:21576368 PMID:21659604 PMID:23429704 PMID:29424687 PMID:29567957 PMID:35926713
In response to nutrients, growth factors or amino acids, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis .
PMID:12087098 PMID:12150925 PMID:12150926 PMID:12231510 PMID:12718876 PMID:14651849 PMID:15268862 PMID:15467718 PMID:15545625 PMID:15718470 PMID:18497260 PMID:18762023 PMID:18925875 PMID:20516213 PMID:20537536 PMID:21659604 PMID:23429703 PMID:23429704 PMID:25799227 PMID:26018084 PMID:29150432 PMID:29236692 PMID:31112131 PMID:34519269
This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) .
PMID:24403073 PMID:29236692
Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4 .
PMID:12087098 PMID:12150925 PMID:18925875 PMID:29150432 PMID:29236692
Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex .
PMID:23429703 PMID:23429704
Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor .
PMID:20516213
Activates dormant ribosomes by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation and reactivation of translation .
PMID:36691768
In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 .
PMID:23426360
To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A (By similarity). In the same time, mTORC1 inhibits catabolic pathways: negatively regulates autophagy through phosphorylation of ULK1 .
PMID:32561715
Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 .
PMID:32561715
Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP .
PMID:20537536
Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions .
PMID:30704899
Prevents autophagy by mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA .
PMID:23524951 PMID:25438055
mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor .
PMID:21659604
Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules .
PMID:12231510
The mTORC1 complex is inhibited in response to starvation and amino acid depletion .
PMID:12150925 PMID:12150926 PMID:24403073 PMID:31695197
The non-canonical mTORC1 complex, which acts independently of RHEB, specifically mediates phosphorylation of MiT/TFE factors MITF, TFEB and TFE3 in the presence of nutrients, promoting their cytosolic retention and inactivation .
PMID:22343943 PMID:22576015 PMID:22692423 PMID:24448649 PMID:32612235 PMID:36608670 PMID:36697823
Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity .
PMID:22343943 PMID:22576015 PMID:22692423 PMID:24448649 PMID:32612235 PMID:36608670
The mTORC1 complex regulates pyroptosis in macrophages by promoting GSDMD oligomerization .
PMID:34289345
MTOR phosphorylates RPTOR which in turn inhibits mTORC1 (By similarity). As part of the mTORC2 complex, MTOR transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output .
PMID:15268862 PMID:15467718 PMID:24670654 PMID:29424687 PMID:29567957 PMID:35926713
In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 .
PMID:15268862 PMID:15467718 PMID:21376236 PMID:24670654 PMID:29424687 PMID:29567957 PMID:35926713
In contrast to mTORC1, mTORC2 is nutrient-insensitive .
PMID:15467718
mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation .
PMID:15718470 PMID:21376236 PMID:24670654 PMID:29424687 PMID:29567957
mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422' .
PMID:18925875
mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B .
PMID:15268862
The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity).
May also regulate insulin signaling by acting as a tyrosine protein kinase that catalyzes phosphorylation of IGF1R and INSR; additional evidence are however required to confirm this result in vivo .
PMID:26584640
Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms (By similarity). Plays an important regulatory role in the circadian clock function; regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks (By similarity)
PMID:12087098 PMID:12150925 PMID:12150926 PMID:12231510 PMID:12718876 PMID:14651849 PMID:15268862 PMID:15467718 PMID:15545625 PMID:15718470 PMID:18497260 PMID:18762023 PMID:18925875 PMID:20516213 PMID:20537536 PMID:21659604 PMID:23429703 PMID:23429704 PMID:25799227 PMID:26018084 PMID:29150432 PMID:29236692 PMID:31112131 PMID:31601708 PMID:32561715 PMID:34519269 PMID:37751742
MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins .
PMID:15268862 PMID:15467718 PMID:17517883 PMID:18372248 PMID:18497260 PMID:18925875 PMID:20516213 PMID:21576368 PMID:21659604 PMID:23429704 PMID:30171069 PMID:29236692 PMID:37751742
Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) .
PMID:15268862 PMID:15467718 PMID:18497260 PMID:18925875 PMID:20516213 PMID:21576368 PMID:21659604 PMID:23429704 PMID:29424687 PMID:29567957 PMID:35926713
In response to nutrients, growth factors or amino acids, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis .
PMID:12087098 PMID:12150925 PMID:12150926 PMID:12231510 PMID:12718876 PMID:14651849 PMID:15268862 PMID:15467718 PMID:15545625 PMID:15718470 PMID:18497260 PMID:18762023 PMID:18925875 PMID:20516213 PMID:20537536 PMID:21659604 PMID:23429703 PMID:23429704 PMID:25799227 PMID:26018084 PMID:29150432 PMID:29236692 PMID:31112131 PMID:34519269
This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) .
PMID:24403073 PMID:29236692
Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4 .
PMID:12087098 PMID:12150925 PMID:18925875 PMID:29150432 PMID:29236692
Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex .
PMID:23429703 PMID:23429704
Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor .
PMID:20516213
Activates dormant ribosomes by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation and reactivation of translation .
PMID:36691768
In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 .
PMID:23426360
To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A (By similarity). In the same time, mTORC1 inhibits catabolic pathways: negatively regulates autophagy through phosphorylation of ULK1 .
PMID:32561715
Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 .
PMID:32561715
Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP .
PMID:20537536
Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions .
PMID:30704899
Prevents autophagy by mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA .
PMID:23524951 PMID:25438055
mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor .
PMID:21659604
Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules .
PMID:12231510
The mTORC1 complex is inhibited in response to starvation and amino acid depletion .
PMID:12150925 PMID:12150926 PMID:24403073 PMID:31695197
The non-canonical mTORC1 complex, which acts independently of RHEB, specifically mediates phosphorylation of MiT/TFE factors MITF, TFEB and TFE3 in the presence of nutrients, promoting their cytosolic retention and inactivation .
PMID:22343943 PMID:22576015 PMID:22692423 PMID:24448649 PMID:32612235 PMID:36608670 PMID:36697823
Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity .
PMID:22343943 PMID:22576015 PMID:22692423 PMID:24448649 PMID:32612235 PMID:36608670
The mTORC1 complex regulates pyroptosis in macrophages by promoting GSDMD oligomerization .
PMID:34289345
MTOR phosphorylates RPTOR which in turn inhibits mTORC1 (By similarity). As part of the mTORC2 complex, MTOR transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output .
PMID:15268862 PMID:15467718 PMID:24670654 PMID:29424687 PMID:29567957 PMID:35926713
In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 .
PMID:15268862 PMID:15467718 PMID:21376236 PMID:24670654 PMID:29424687 PMID:29567957 PMID:35926713
In contrast to mTORC1, mTORC2 is nutrient-insensitive .
PMID:15467718
mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation .
PMID:15718470 PMID:21376236 PMID:24670654 PMID:29424687 PMID:29567957
mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422' .
PMID:18925875
mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B .
PMID:15268862
The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity).
May also regulate insulin signaling by acting as a tyrosine protein kinase that catalyzes phosphorylation of IGF1R and INSR; additional evidence are however required to confirm this result in vivo .
PMID:26584640
Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms (By similarity). Plays an important regulatory role in the circadian clock function; regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks (By similarity)
Metabolizing enzymes(3)
Enzymes involved in drug metabolism — important for understanding drug interactions
Enzyme activity key
substrate
inhibitor
inducer
CYP2C8Cytochrome P450 2C8
substrate
CYP3A4Cytochrome P450 3A4
substrate
UGT1A9UDP-glucuronosyltransferase 1A9
substrate
Transporters(4)
Proteins that transport this drug across cell membranes
ATP-dependent translocase ABCB1
ABCB1
substrate
inhibitor
Specific functionABC-type xenobiotic transporter activity
Cellular location
Cell membrane
General function & pharmacology
Translocates drugs and phospholipids across the membrane .
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
Broad substrate specificity ATP-binding cassette transporter ABCG2
ABCG2
substrate
inhibitor
Specific functionABC-type xenobiotic transporter activity
Cellular location
Cell membrane
General function & pharmacology
Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells .
PMID:11306452 PMID:12958161 PMID:19506252 PMID:20705604 PMID:28554189 PMID:30405239 PMID:31003562
Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme .
PMID:20705604 PMID:23189181
Also mediates the efflux of sphingosine-1-P from cells .
PMID:20110355
Acts as a urate exporter functioning in both renal and extrarenal urate excretion .
PMID:19506252 PMID:20368174 PMID:22132962 PMID:31003562 PMID:36749388
In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates .
PMID:12682043 PMID:28554189 PMID:30405239
Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity).
Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux .
PMID:11306452 PMID:12477054 PMID:15670731 PMID:18056989 PMID:31254042
In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity).
In inflammatory macrophages, exports itaconate from the cytosol to the extracellular compartment and limits the activation of TFEB-dependent lysosome biogenesis involved in antibacterial innate immune response
PMID:11306452 PMID:12958161 PMID:19506252 PMID:20705604 PMID:28554189 PMID:30405239 PMID:31003562
Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme .
PMID:20705604 PMID:23189181
Also mediates the efflux of sphingosine-1-P from cells .
PMID:20110355
Acts as a urate exporter functioning in both renal and extrarenal urate excretion .
PMID:19506252 PMID:20368174 PMID:22132962 PMID:31003562 PMID:36749388
In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates .
PMID:12682043 PMID:28554189 PMID:30405239
Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity).
Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux .
PMID:11306452 PMID:12477054 PMID:15670731 PMID:18056989 PMID:31254042
In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity).
In inflammatory macrophages, exports itaconate from the cytosol to the extracellular compartment and limits the activation of TFEB-dependent lysosome biogenesis involved in antibacterial innate immune response
Multidrug and toxin extrusion protein 1
SLC47A1
inhibitor
Specific functionantiporter activity
Cellular location
Cell membrane
General function & pharmacology
Multidrug efflux pump that functions as a H(+)/organic cation antiporter .
PMID:16330770 PMID:17509534
Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively .
PMID:16330770 PMID:17495125 PMID:17509534 PMID:17582384 PMID:18305230 PMID:19158817 PMID:21128598 PMID:24961373
Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate .
PMID:16330770 PMID:17495125 PMID:17509534 PMID:17582384 PMID:18305230 PMID:19158817 PMID:21128598 PMID:24961373
May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable)
PMID:16330770 PMID:17509534
Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively .
PMID:16330770 PMID:17495125 PMID:17509534 PMID:17582384 PMID:18305230 PMID:19158817 PMID:21128598 PMID:24961373
Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate .
PMID:16330770 PMID:17495125 PMID:17509534 PMID:17582384 PMID:18305230 PMID:19158817 PMID:21128598 PMID:24961373
May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable)
Multidrug and toxin extrusion protein 2
SLC47A2
inhibitor
Specific functionantiporter activity
Cellular location
Cell membrane
General function & pharmacology
Multidrug efflux pump that functions as a H(+)/organic cation antiporter. Mediates the efflux of cationic compounds, such as the model cations, tetraethylammonium (TEA) and 1-methyl-4-phenylpyridinium (MPP+), the platinum-based drug oxaliplatin or weak bases that are positively charged at physiological pH, cimetidine, the platinum-based drugs cisplatin and oxaliplatin or the antidiabetic drug metformin. Mediates the efflux of endogenous compounds such as, creatinine, thiamine and estrone-3-sulfate.
Plays a physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney
Plays a physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney
Carriers(2)
Proteins that carry this drug through the body
Albumin
ALB
binder
Specific functionantioxidant activity
Cellular location
Secreted
General function & pharmacology
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc .
PMID:19021548
Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity).
Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity).
Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli .
PMID:6234017
Does not prevent iron uptake by the bacterial siderophore aerobactin PMID:6234017
PMID:19021548
Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity).
Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity).
Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli .
PMID:6234017
Does not prevent iron uptake by the bacterial siderophore aerobactin PMID:6234017
Alpha-1-acid glycoprotein 2
ORM2
binder
Cellular location
Secreted
General function & pharmacology
Functions as a transport protein in the blood stream. Binds various hydrophobic ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability.
Appears to function in modulating the activity of the immune system during the acute-phase reaction
Appears to function in modulating the activity of the immune system during the acute-phase reaction
Scientific references(7)
Munchhof M.J., Li Q., Shavnya A., Borzillo G.V., Boyden T.L., Jones C.S., LaGreca S.D., Martinez-Alsina L., Patel N., Pelletier K., Reiter L.A., Robbins M.D., Tkalcevic G.T.
Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
ACS Medicine Chemistry Lett
2011 Dec 213(2):106-11. doi: 10.1021/ml2002423. eCollection 2012 Feb 9
Minami Y., Minami H., Miyamoto T., Yoshimoto G., Kobayashi Y., Munakata W., Onishi Y., Kobayashi M., Ikuta M., Chan G., Woolfson A., Ono C., Shaik M.N., Fujii Y., Zheng X., Naoe T.
Phase I study of glasdegib (PF-04449913), an oral smoothened inhibitor, in Japanese patients with select hematologic malignancies.
Cancer Science
2017 Aug108(8):1628-1633. doi: 10.1111/cas.13285. Epub 2017 Jun 19
Irvine D.A., Copland M.
Targeting hedgehog in hematologic malignancy.
Blood
2012 Mar 8119(10):2196-204. doi: 10.1182/blood-2011-10-383752. Epub 2012 Jan 5
Lam J.L., Vaz A., Hee B., Liang Y., Yang X., Shaik M.N.
Metabolism, excretion and pharmacokinetics of [(14)C]glasdegib (PF-04449913) in healthy volunteers following oral administration.
Xenobiotica
2017 Dec47(12):1064-1076. doi: 10.1080/00498254.2016.1261307. Epub 2017 Jan 3
Iyer S.G., Stanchina M., Bradley T.J., Watts J.
Profile of Glasdegib for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML): Evidence to Date.
Cancer Manag Research
2022 Aug 114:2267-2272. doi: 10.2147/CMAR.S195723. eCollection 2022
Jamieson C., Martinelli G., Papayannidis C., Cortes J.E.
Hedgehog Pathway Inhibitors: A New Therapeutic Class for the Treatment of Acute Myeloid Leukemia.
Blood Cancer Discov
2020 Aug 111(2):134-145. doi: 10.1158/2643-3230.BCD-20-0007. eCollection 2020 Sep
Terao T., Minami Y.
Targeting Hedgehog (Hh) Pathway for the Acute Myeloid Leukemia Treatment.
Cells
2019 Apr 38(4):312. doi: 10.3390/cells8040312
ATC classification(1 code)
ATC L01XJ03
Affected organisms(1)
Humans and other mammals
Salt forms(2)
Glasdegib hydrochloride(DBSALT002116)
Glasdegib maleate(DBSALT003035)
Experimental properties(4)
Commercial products(8)
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Show
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Linked compound data from DrugBank Open Data (CC BY-NC 4.0)
Glasdegib
Additional database identifiers
Drugs Product Database (DPD)
23451
ChemSpider
28518072
BindingDB
50385635
ZINC
ZINC000068251434
HUGO Gene Nomenclature Committee (HGNC)
HGNC:11119
GeneCards
SMO
Guide to Pharmacology
239
UniProt Accession
SMO_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:3942
GenAtlas
FRAP1
GeneCards
MTOR
GenBank Gene Database
L34075
Guide to Pharmacology
2109
UniProt Accession
MTOR_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2622
GenAtlas
CYP2C8
GeneCards
CYP2C8
GenBank Gene Database
M17397
Guide to Pharmacology
1325
UniProt Accession
CP2C8_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2637
GenAtlas
CYP3A4
GeneCards
CYP3A4
GenBank Gene Database
M18907
Guide to Pharmacology
1337
UniProt Accession
CP3A4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12541
GeneCards
UGT1A9
GenBank Gene Database
S55985
GenBank Protein Database
7690346
UniProt Accession
UD19_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:399
GenAtlas
ALB
GeneCards
ALB
GenBank Gene Database
V00494
GenBank Protein Database
28590
UniProt Accession
ALBU_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8498
GenAtlas
ORM1
GeneCards
ORM1
GenBank Gene Database
X02544
GenBank Protein Database
757907
UniProt Accession
A1AG1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8499
GeneCards
ORM2
GenBank Gene Database
BC015964
GenBank Protein Database
16359000
UniProt Accession
A1AG2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:40
GenAtlas
ABCB1
GeneCards
ABCB1
GenBank Gene Database
M14758
GenBank Protein Database
307180
Guide to Pharmacology
768
UniProt Accession
MDR1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:74
GenAtlas
ABCG2
GeneCards
ABCG2
GenBank Gene Database
AF103796
GenBank Protein Database
4185796
Guide to Pharmacology
792
UniProt Accession
ABCG2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:25588
GeneCards
SLC47A1
GenBank Gene Database
AK001709
GenBank Protein Database
7023138
Guide to Pharmacology
1216
UniProt Accession
S47A1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:26439
GeneCards
SLC47A2
Guide to Pharmacology
1217
UniProt Accession
S47A2_HUMAN
Patent information
5 active patents
10414748
United States
Approved 17 Sept 2019 · Expires 13 Apr 2036
10 years
11168066
United States
Approved 9 Nov 2021 · Expires 13 Apr 2036
10 years
11891372
United States
Approved 6 Feb 2024 · Expires 13 Apr 2036
10 years
8148401
United States
Approved 3 Apr 2012 · Expires 30 Jan 2031
4y 10m
8431597
United States
Approved 30 Apr 2013 · Expires 29 Jun 2028
2y 2m
Source: DrugBank · CC BY-NC 4.0. Patent data sourced from national patent offices. Expiry dates may not reflect extensions, regulatory exclusivity periods, or legal challenges.
DrugBank citations
If you use DrugBank data in your research, please cite the following publications:
Knox C., Wilson M., Klinger C.M., et al
DrugBank 6.
0: the DrugBank Knowledgebase for 2024
Nucleic Acids Res. 2024 Jan 552(D1):D1265-D1275
Wishart D.S., Feunang Y.D., Guo A.C., et al
DrugBank 5.
0: a major update to the DrugBank database for 2018
Nucleic Acids Res. 2017 Nov 846(D1):D1074-D1082
Show earlier publications
Law V., Knox C., Djoumbou Y., et al
DrugBank 4.
0: shedding new light on drug metabolism
Nucleic Acids Res. 2014 Jan 142(1):D1091-7
Knox C., Law V., Jewison T., et al
DrugBank 3.
0: a comprehensive resource for 'omics' research on drugs
Nucleic Acids Res. 2011 Jan39(Database issue):D1035-41
Wishart D.S., Knox C., Guo A.C., et al
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Source: go.drugbank.comCC BY-NC 4.0
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