Leniolisib 70mg tablets
Prescription only
Requires a prescription from a doctor or prescriber
Tablet
70mg
Oral
Leniolisib is a potent and selective inhibitor of phosphoinositide 3-kinase δ (PI3Kδ).
Active ingredients:
Leniolisib
No active safety alerts
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Safety monitoring data
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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.
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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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Joenja 70mg tablets
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Clinical guidelines and formulary information
British National Formulary
Leniolisib
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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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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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
10 hours
Mechanism
Phosphoinositide-3-kinase δ (PI3Kδ) is a lipid kinase activated downstream of ty…
Food interactions
1 warning
Human targets
1 target
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
12 hours
The systemic drug exposure (AUC and Cmax) of leniolisib increases dose proportionally.…
Half-life
10 hours
The effective half-life is approximately seven hours. The apparent terminal elimination half-life is approximately 10 hours.
[L45753]
[L45753]
Protein binding
94.5%
Leniolisib is 94.5% bound to plasma proteins.
[L45753]
[L45753]
Volume of distribution
28.5 L
The systemic decay in leniolisib plasma concentration over time is bi-exponential, indicating a distribution delay toward peripheral tissues.…
Metabolism
60%
About 60% of leniolisib is metabolized by the liver. Leniolisib undergoes oxidative metabolism, which is primarily mediated by CYP3A4 (94.5%),…
Elimination
70 mg
The mean recovery of total 14C-radioactivity following a single oral dose of 70 mg 14C-leniolisib was 92.5%…
Clearance
400 mg
In one study, healthy volunteers received leniolisib single ascending doses up to 400 mg and multiple ascending doses up to 140 mg twice daily for 14 days.…
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Status:
Approved
Investigational
Small molecule
About this compound
Leniolisib is a potent and selective inhibitor of phosphoinositide 3-kinase δ (PI3Kδ). The FDA approved leniolisib on March 24, 2023, making it the first treatment for activated phosphoinositide 3-kinase delta syndrome (APDS).[L45758] APDS is a primary immunodeficiency caused by mutations in genes encoding the PI3Kδ, thereby increasing the activity of PI3Kδ, causing immune dysfunction, and elevating susceptibility to infections.[A258473][A258463] Leniolisib works to inhibit hyperactive PI3Kδ.[L45753] Investigations for using leniolisib in primary Sjögren’s syndrome are ongoing.[A258468]
Properties:
solid
Avg. mass: 450.47 Da
DrugBank indication
Leniolisib is indicated for the treatment of activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) in adult and pediatric patients 12 years of age and older.
[L45753]
[L45753]
Also known as(89)
Cdz-173 free base
Cdz173 free base
Leniolisib
2.7.1.137
2.7.1.153
p110delta
Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta
PI3-kinase subunit delta
Dosage forms(1)
Tablet, film coated (Oral) — 70 mg/1
Molecular properties(17)
Drug interactions(336)
Known interactions with other medications. Always consult a healthcare professional.
Zolmitriptan
Moderate
The metabolism of Zolmitriptan can be decreased when combined with Leniolisib.
Eluxadoline
Unknown severity
The excretion of Eluxadoline can be decreased when combined with Leniolisib.
Folic acid
Unknown severity
The excretion of Folic acid can be decreased when combined with Leniolisib.
Pravastatin
Unknown severity
The excretion of Pravastatin can be decreased when combined with Leniolisib.
Conjugated estrogens
Unknown severity
The excretion of Conjugated estrogens can be decreased when combined with Leniolisib.
The excretion of Gefitinib can be decreased when combined with Leniolisib.
Allopurinol
Unknown severity
The excretion of Allopurinol can be decreased when combined with Leniolisib.
Cerivastatin
Unknown severity
The excretion of Cerivastatin can be decreased when combined with Leniolisib.
Teniposide
Unknown severity
The excretion of Teniposide can be decreased when combined with Leniolisib.
The excretion of Prazosin can be decreased when combined with Leniolisib.
Raloxifene
Unknown severity
The excretion of Raloxifene can be decreased when combined with Leniolisib.
The excretion of Celecoxib can be decreased when combined with Leniolisib.
Zidovudine
Unknown severity
The excretion of Zidovudine can be decreased when combined with Leniolisib.
The excretion of Ritonavir can be decreased when combined with Leniolisib.
Oxaliplatin
Unknown severity
The excretion of Oxaliplatin can be decreased when combined with Leniolisib.
Vincristine
Unknown severity
The excretion of Vincristine can be decreased when combined with Leniolisib.
Fluorouracil
Moderate
The metabolism of Fluorouracil can be decreased when combined with Leniolisib.
Methotrexate
Unknown severity
The excretion of Methotrexate can be decreased when combined with Leniolisib.
Ivermectin
Unknown severity
The excretion of Ivermectin can be decreased when combined with Leniolisib.
The excretion of Imatinib can be decreased when combined with Leniolisib.
Testosterone
Unknown severity
The excretion of Testosterone can be decreased when combined with Leniolisib.
Clofarabine
Unknown severity
The excretion of Clofarabine can be decreased when combined with Leniolisib.
Sumatriptan
Unknown severity
The excretion of Sumatriptan can be decreased when combined with Leniolisib.
The metabolism of Tamoxifen can be decreased when combined with Leniolisib.
Mycophenolate mofetil
Unknown severity
The excretion of Mycophenolate mofetil can be decreased when combined with Leniolisib.
Daunorubicin
Unknown severity
The excretion of Daunorubicin can be decreased when combined with Leniolisib.
Nitrofurantoin
Unknown severity
The excretion of Nitrofurantoin can be decreased when combined with Leniolisib.
Lamivudine
Unknown severity
The excretion of Lamivudine can be decreased when combined with Leniolisib.
The excretion of Riluzole can be decreased when combined with Leniolisib.
Irinotecan
Unknown severity
The excretion of Irinotecan can be decreased when combined with Leniolisib.
The metabolism of Etoposide can be decreased when combined with Leniolisib.
Sulfasalazine
Unknown severity
The excretion of Sulfasalazine can be decreased when combined with Leniolisib.
The excretion of Donepezil can be decreased when combined with Leniolisib.
Dactinomycin
Unknown severity
The excretion of Dactinomycin can be decreased when combined with Leniolisib.
The excretion of Ezetimibe can be decreased when combined with Leniolisib.
Doxorubicin
Unknown severity
The excretion of Doxorubicin can be decreased when combined with Leniolisib.
The excretion of Glyburide can be decreased when combined with Leniolisib.
The excretion of Topotecan can be decreased when combined with Leniolisib.
The excretion of Tegaserod can be decreased when combined with Leniolisib.
Leflunomide
Unknown severity
The excretion of Leflunomide can be decreased when combined with Leniolisib.
Rosuvastatin
Unknown severity
The excretion of Rosuvastatin can be decreased when combined with Leniolisib.
Mitoxantrone
Unknown severity
The excretion of Mitoxantrone can be decreased when combined with Leniolisib.
The metabolism of Dasatinib can be decreased when combined with Leniolisib.
The excretion of Alvocidib can be decreased when combined with Leniolisib.
Camptothecin
Unknown severity
The excretion of Camptothecin can be decreased when combined with Leniolisib.
The excretion of Nilotinib can be decreased when combined with Leniolisib.
Rivaroxaban
Unknown severity
The excretion of Rivaroxaban can be decreased when combined with Leniolisib.
Simeprevir
Unknown severity
The excretion of Simeprevir can be decreased when combined with Leniolisib.
The excretion of Pazopanib can be decreased when combined with Leniolisib.
The excretion of Apixaban can be decreased when combined with Leniolisib.
Showing 50 of 336 interactions
Food & lifestyle interactions
Advice
Take with or without food. Food has negligible effects on systemic exposure of leniolisib.
Toxicity & overdose
No information on the LD50 of leniolisib is available. If overdosage occurs, monitor the patient for any signs or symptoms of adverse reactions. Treatment of overdose with leniolisib consists of general supportive measures, including monitoring of vital signs as well as observation of the clinical status of the patient.
[L45753]
[L45753]
How it works
Mechanism of action
Phosphoinositide-3-kinase δ (PI3Kδ) is a lipid kinase activated downstream of tyrosine kinase receptors and G-protein–coupled receptors in immune cells.[A258473][A258468][A258518] It mediates the PI3K/AKT pathway, which is involved in cell proliferation, growth, and survival.[A258508][A258513] A heterodimer made up of a regulatory subunit (p85α) and a catalytic subunit (p110δ), PI3Kδ is primarily expressed on hematopoietic cells such as lymphocytes and myeloid cells. It converts phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-trisphosphate (PIP3), a signalling molecule that downstream proteins like the AKT kinase, which activate mammalian target of rapamycin (mTOR) complex I and inhibit FOXO family of transcription factors.[A258473][A258463] APDS is associated with gain-of-function variants in the gene encoding p110δ or loss of function variants in the gene encoding p85α, each causing hyperactivity of PI3K-delta, reduced T cell function, lymphadenopathy, and immunodeficiency.[A258473][L45753]
Leniolisib inhibits PI3Kδ by blocking the active binding site in the p110δ subunit.[A258463] In cell-free isolated enzyme assays, the selectivity was higher for PI3K-delta over PI3K-alpha (28-fold), PI3K-beta (43-fold), and PI3K-gamma (257-fold), as well as the broader kinome. In cell-based assays, leniolisib reduced pAKT pathway activity and inhibited proliferation and activation of B and T cell subsets. Leniolisib inhibits the signalling pathways that lead to increased production of PIP3, hyperactivity of the downstream mTOR/AKT pathway, and the dysregulation of B and T cells.[L45753]
Leniolisib inhibits PI3Kδ by blocking the active binding site in the p110δ subunit.[A258463] In cell-free isolated enzyme assays, the selectivity was higher for PI3K-delta over PI3K-alpha (28-fold), PI3K-beta (43-fold), and PI3K-gamma (257-fold), as well as the broader kinome. In cell-based assays, leniolisib reduced pAKT pathway activity and inhibited proliferation and activation of B and T cell subsets. Leniolisib inhibits the signalling pathways that lead to increased production of PIP3, hyperactivity of the downstream mTOR/AKT pathway, and the dysregulation of B and T cells.[L45753]
Pharmacodynamics
Leniolisib works to block aberrant PI3Kδ-dependent signalling pathways of immune cells, such as B and T cells, neutrophils, monocytes, basophils, plasmocytoid dendritic cells, and mast cells.[A258468] In vitro, leniolisib dose-dependently suppresses the PI3Kδ pathway hyperactivation in cell lines overexpressing p110δ mutants and in primary immune cells from patients with APDS.[A258463] Ex vivo pharmacodynamics of leniolisib in the proportion of phosphorylated Akt (pAkt)- positive B cells were assessed intra-individually at 10, 30, and 70 mg twice daily for four weeks at each dose level in patients with APDS. Within the explored dose range, higher leniolisib plasma concentrations were generally associated with a higher reduction of pAkt-positive B cells. Higher doses were associated with a slightly higher peak and more sustained reduction. Treatment with leniolisib 70 mg twice a day at a steady state is estimated to produce a time-averaged reduction of pAkt-positive B cells by approximately 80%.[L45753]
Pharmacokinetics
How the body processes this drug — absorption, distribution, metabolism, and elimination
Absorption
The systemic drug exposure (AUC and Cmax) of leniolisib increases dose proportionally. During twice daily dosing approximately 12 hours apart, leniolisib accumulates approximately 1.4-fold (range of 1.0 to 2.2) in achieving steady-state. Steady-state drug concentrations can be expected to be reached after approximately two to three days.
The Tmax is about one hour. Food has negligible effects on the systemic exposure of leniolisib.
[L45753]
The Tmax is about one hour. Food has negligible effects on the systemic exposure of leniolisib.
[L45753]
Half-life
The effective half-life is approximately seven hours. The apparent terminal elimination half-life is approximately 10 hours.
[L45753]
[L45753]
Protein binding
Leniolisib is 94.5% bound to plasma proteins.
[L45753]
[L45753]
Volume of distribution
The systemic decay in leniolisib plasma concentration over time is bi-exponential, indicating a distribution delay toward peripheral tissues. The volume of distribution of leniolisib is estimated to be 28.5 L in patients with APDS.
[L45753]
[L45753]
Metabolism
About 60% of leniolisib is metabolized by the liver. Leniolisib undergoes oxidative metabolism, which is primarily mediated by CYP3A4 (94.5%), as well as CYP3A5 (3.5%), CYP1A2 (0.7%) and CYP2D6 (0.7%) to a minor extent.
[A258478][L45753]
Few metabolites of leniolisib have been characterized in one study; however, no metabolites were abundant in plasma relative to the parent drug. Other metabolic pathways include dealkylation, demethylation, and hydroxylation.
[A258483]
Other suggested excretion routes include intestinal secretion by BCRP and CYP1A1-mediated extrahepatic metabolism.
[A258478][L45753]
[A258478][L45753]
Few metabolites of leniolisib have been characterized in one study; however, no metabolites were abundant in plasma relative to the parent drug. Other metabolic pathways include dealkylation, demethylation, and hydroxylation.
[A258483]
Other suggested excretion routes include intestinal secretion by BCRP and CYP1A1-mediated extrahepatic metabolism.
[A258478][L45753]
Route of elimination
The mean recovery of total 14C-radioactivity following a single oral dose of 70 mg 14C-leniolisib was 92.5% following 168 hours post-dose. About 67% and 25.5% of the recovered dose were in feces and urine, respectively. Of the recovered dose in urine, 6.32% was in unchanged parent drug form and the predominant drug-related material.
[L45753]
[L45753]
Clearance
In one study, healthy volunteers received leniolisib single ascending doses up to 400 mg and multiple ascending doses up to 140 mg twice daily for 14 days. Oral drug clearance from plasma (CL/F) was 4 L/h.
[A258478]
[A258478]
Drug targets(1)
Proteins and enzymes this drug interacts with in the body
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
PIK3CD
inhibitor
Specific function1-phosphatidylinositol-3-kinase activity
Cellular location
Cytoplasm
General function & pharmacology
Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides .
PMID:9235916
Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) .
PMID:15135396
PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function.
Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9.
Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P).
Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse.
Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation.
Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation.
Plays a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst.
Plays important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release.
The lipid kinase activity is required for its biological function. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity
PMID:9235916
Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) .
PMID:15135396
PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function.
Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9.
Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P).
Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse.
Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation.
Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation.
Plays a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst.
Plays important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release.
The lipid kinase activity is required for its biological function. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity
Metabolizing enzymes(5)
Enzymes involved in drug metabolism — important for understanding drug interactions
Enzyme activity key
substrate
inhibitor
inducer
CYP1A2Cytochrome P450 1A2
substrate
inhibitor
CYP3A4Cytochrome P450 3A4
substrate
CYP3A5Cytochrome P450 3A5
substrate
CYP2D6Cytochrome P450 2D6
substrate
CYP1A1Cytochrome P450 1A1
substrate
Transporters(4)
Proteins that transport this drug across cell membranes
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
Solute carrier organic anion transporter family member 1B1
SLCO1B1
inhibitor
Specific functionbile acid transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Mediates the Na(+)-independent uptake of organic anions .
PMID:10358072 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) .
PMID:10358072 PMID:10601278 PMID:10873595 PMID:11159893 PMID:12196548 PMID:12568656 PMID:15159445 PMID:15970799 PMID:16627748 PMID:17412826 PMID:19129463 PMID:26979622
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Involved in the clearance of endogenous and exogenous substrates from the liver .
PMID:10358072 PMID:10601278
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:10601278 PMID:15159445 PMID:15970799
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver .
PMID:16624871 PMID:16627748
Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions PMID:19129463
PMID:10358072 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) .
PMID:10358072 PMID:10601278 PMID:10873595 PMID:11159893 PMID:12196548 PMID:12568656 PMID:15159445 PMID:15970799 PMID:16627748 PMID:17412826 PMID:19129463 PMID:26979622
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Involved in the clearance of endogenous and exogenous substrates from the liver .
PMID:10358072 PMID:10601278
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:10601278 PMID:15159445 PMID:15970799
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver .
PMID:16624871 PMID:16627748
Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions PMID:19129463
Solute carrier organic anion transporter family member 1B3
SLCO1B3
inhibitor
Specific functionbile acid transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Mediates the Na(+)-independent uptake of organic anions .
PMID:10779507 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) .
PMID:10779507 PMID:11159893 PMID:12568656 PMID:15159445 PMID:17412826 PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions .
PMID:19129463
Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Involved in the clearance of bile acids and organic anions from the liver .
PMID:22232210
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:15159445
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver PMID:16624871 PMID:16627748
PMID:10779507 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) .
PMID:10779507 PMID:11159893 PMID:12568656 PMID:15159445 PMID:17412826 PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions .
PMID:19129463
Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Involved in the clearance of bile acids and organic anions from the liver .
PMID:22232210
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:15159445
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver PMID:16624871 PMID:16627748
ATP-dependent translocase ABCB1
ABCB1
substrate
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
Scientific references(8)
Michalovich D., Nejentsev S.
Activated PI3 Kinase Delta Syndrome: From Genetics to Therapy.
Front Immunology
2018 Feb 279:369. doi: 10.3389/fimmu.2018.00369. eCollection 2018
Rao V.K., Webster S., Dalm VASH, Sediva A., van Hagen P.M., Holland S., Rosenzweig S.D., Christ A.D., Sloth B., Cabanski M., Joshi A.D., de Buck S., Doucet J., Guerini D., Kalis C., Pylvaenaeinen I., Soldermann N., Kashyap A., Uzel G., Lenardo M.J., Patel D.D., Lucas C.L., Burkhart C.
Effective "activated PI3Kdelta syndrome"-targeted therapy with the PI3Kdelta inhibitor leniolisib.
Blood
2017 Nov 23130(21):2307-2316. doi: 10.1182/blood-2017-08-801191. Epub 2017 Sep 29
Hoegenauer K., Soldermann N., Zecri F., Strang R.S., Graveleau N., Wolf R.M., Cooke N.G., Smith A.B., Hollingworth G.J., Blanz J., Gutmann S., Rummel G., Littlewood-Evans A., Burkhart C.
Discovery of CDZ173 (Leniolisib), Representing a Structurally Novel Class of PI3K Delta-Selective Inhibitors.
ACS Medicine Chemistry Lett
2017 Aug 258(9):975-980. doi: 10.1021/acsmedchemlett.7b00293. eCollection 2017 Sep 14
De Buck S., Kucher K., Hara H., Gray C., Woessner R.
CYP3A but not P-gp plays a relevant role in the in vivo intestinal and hepatic clearance of the delta-specific phosphoinositide-3 kinase inhibitor leniolisib.
Biopharm Drug Disposition
2018 Sep39(8):394-402. doi: 10.1002/bdd.2157
Pearson D., Garnier M., Luneau A., James A.D., Walles M.
(19)F-NMR-based determination of the absorption, metabolism and excretion of the oral phosphatidylinositol-3-kinase (PI3K) delta inhibitor leniolisib (CDZ173) in healthy volunteers.
Xenobiotica
2019 Aug49(8):953-960. doi: 10.1080/00498254.2018.1523488. Epub 2018 Nov 29
Fresno Vara J.A., Casado E., de Castro J., Cejas P., Belda-Iniesta C., Gonzalez-Baron M.
PI3K/Akt signalling pathway and cancer.
Cancer Treat Review
2004 Apr30(2):193-204. doi: 10.1016/j.ctrv.2003.07.007
Osaki M., Oshimura M., Ito H.
PI3K-Akt pathway: its functions and alterations in human cancer.
Apoptosis
2004 Nov9(6):667-76. doi: 10.1023/B:APPT.0000045801.15585.dd
Martini M., De Santis M.C., Braccini L., Gulluni F., Hirsch E.
PI3K/AKT signaling pathway and cancer: an updated review.
Ann Medicine
2014 Sep46(6):372-83. doi: 10.3109/07853890.2014.912836. Epub 2014 Jun 5
ATC classification(1 code)
ATC L03AX22
Salt forms(1)
Leniolisib phosphate(DBSALT003336)
Experimental properties(1)
Protein Data Bank entries(1)
Commercial products(1)
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)
Leniolisib
Additional database identifiers
ChemSpider
52083264
BindingDB
118299
PDB
9NQ
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8977
GenAtlas
PIK3CD
GeneCards
PIK3CD
GenBank Gene Database
Y10055
Guide to Pharmacology
2155
UniProt Accession
PK3CD_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2596
GenAtlas
CYP1A2
GeneCards
CYP1A2
GenBank Gene Database
Z00036
Guide to Pharmacology
1319
UniProt Accession
CP1A2_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:2638
GenAtlas
CYP3A5
GeneCards
CYP3A5
GenBank Gene Database
J04813
GenBank Protein Database
181346
Guide to Pharmacology
1338
UniProt Accession
CP3A5_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2625
GenAtlas
CYP2D6
GeneCards
CYP2D6
GenBank Gene Database
M20403
GenBank Protein Database
181350
Guide to Pharmacology
1329
UniProt Accession
CP2D6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2595
GeneCards
CYP1A1
GenBank Gene Database
K03191
GenBank Protein Database
181276
Guide to Pharmacology
1318
UniProt Accession
CP1A1_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:10959
GenAtlas
SLCO1B1
GeneCards
SLCO1B1
GenBank Gene Database
AF060500
GenBank Protein Database
5051630
Guide to Pharmacology
1220
UniProt Accession
SO1B1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10961
GeneCards
SLCO1B3
GenBank Gene Database
AJ251506
GenBank Protein Database
9187497
Guide to Pharmacology
1221
UniProt Accession
SO1B3_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
Patent information
1 active patent
8653092
United States
Approved 18 Feb 2014 · Expires 19 Feb 2032
5y 10m
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
DrugBank: a knowledgebase for drugs, drug actions and drug targets.
Nucleic Acids Research
2008 Jan36(Database issue):D901-6
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a comprehensive resource for in silico drug discovery and exploration.
Nucleic Acids Research
2006 Jan 134(Database issue):D668-72
Source: go.drugbank.comCC BY-NC 4.0
Updated 30 days ago(4 Mar 2026)