Larotrectinib 25mg capsules
Prescription only
Requires a prescription from a doctor or prescriber
Capsule
25mg
Oral
Active ingredients:
Larotrectinib
1 safety notice
Safety information for pregnancy and breastfeeding
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Safety monitoring data
Yellow Card reports
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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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Suspected adverse reactions reported for Larotrectinib
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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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Clinical guidelines and formulary information
British National Formulary
Larotrectinib
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(10)
Larotrectinib for treating NTRK fusion-positive solid tumours (TA630)
TA630
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Updated Mar 2026Source: 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
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Codes for healthcare professionals and prescribing systems
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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
2.9 hours
Mechanism
Tropomysoin receptor kinases (TRK) like TRKA, TRKB, and TRKC elicit activities t…
Food interactions
3 warnings
Human targets
3 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
34%
The mean absolute bioavailability of larotrectinib capsules is approximately 34% (range: 32-37%).
[L49816]…
[L49816]…
Half-life
2.9 hours
In healthy subjects, the half-life of larotrectinib following oral administration is 2.9 hours.
[L49816]
[L49816]
Protein binding
70%
Larotrectinib is 70% bound to human plasma proteins in vitro and binding is independent of drug concentration.
[L49816]…
[L49816]…
Volume of distribution
48L
Following intravenous administration to healthy subjects, the mean volume of distribution of larotrectinib at steady-state was approximately 48L.
[L49816]…
[L49816]…
Metabolism
100 mg
Larotrectinib is metabolized predominantly by CYP3A4.
[L49816]
Following oral administration of a single 100 mg dose of radiolabeled larotrectinib…
[L49816]
Following oral administration of a single 100 mg dose of radiolabeled larotrectinib…
Elimination
100 mg
Following oral administration of a single 100 mg dose of radiolabeled larotrectinib in healthy subjects, 58% (5% unchanged) of the administered…
Clearance
98 L/h
The mean clearance CL/F of larotrectinib is 98 L/h.
[L49816]
[L49816]
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Status:
Approved
Investigational
Small molecule
About this compound
Larotrectinib is an orally administered inhibitor of tropomyosin receptor kinase (Trk), a receptor tyrosine kinase activated by neurotrophins which is mutated in a variety of cancer cell types and plays an important role in tumor cell growth and survival.[L49821] Upon administration, larotrectinib binds to Trk, thereby preventing neurotrophin-Trk interaction and Trk activation, which results in both the induction of cellular apoptosis and the inhibition of cell growth in tumors that overexpress Trk.[L49821]
Larotrectinib was granted accelerated approval by the FDA in November 2018 for the treatment of Trk-positive solid tumors. It was notable for being the second tissue-agnostic chemotherapy ever approved by the FDA.[L4847]. On April 10, 2025, the FDA granted full drug approval.[L52805]
Larotrectinib was granted accelerated approval by the FDA in November 2018 for the treatment of Trk-positive solid tumors. It was notable for being the second tissue-agnostic chemotherapy ever approved by the FDA.[L4847]. On April 10, 2025, the FDA granted full drug approval.[L52805]
Properties:
View FDA drug labelsolid
Avg. mass: 428.44 Da
DrugBank indication
Larotrectinib is a tyrosine kinase inhibitor that is currently indicated for the treatment of adult and pediatric patients with solid tumors that a) have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, b) are metastatic or where surgical resection is likely to result in severe morbidity, or c) have no satisfactory alternative treatments or that have progressed following treatment.
[L49816]
These indications are approved under accelerated approval by the US FDA based on overall response rate and duration of response and continuation of support for these indications may be contingent upon the verification and description of continued clinical benefit in confirmatory trials.
[L49816]
[L49816]
These indications are approved under accelerated approval by the US FDA based on overall response rate and duration of response and continuation of support for these indications may be contingent upon the verification and description of continued clinical benefit in confirmatory trials.
[L49816]
Also known as(58)
Larotrectinib
2.7.10.1
GP145-TrkB
Neurotrophic tyrosine kinase receptor type 2
Trk-B
TRKB
TrkB tyrosine kinase
Tropomyosin-related kinase B
Dosage forms(13)
(Oral) — 100 mg
(Oral) — 25 mg
Capsule (Oral) — 100 mg
Capsule (Oral) — 100 mg/1
Capsule (Oral) — 25 mg
Capsule (Oral) — 25 mg/1
Solution (Oral) — 20 MG/ML
Solution (Oral) — 20 mg / mL
Molecular properties(19)
Drug interactions(171)
Known interactions with other medications. Always consult a healthcare professional.
Propacetamol
Unknown severity
The serum concentration of Propacetamol can be increased when it is combined with Larotrectinib.
Acetaminophen
Unknown severity
The serum concentration of Acetaminophen can be increased when it is combined with Larotrectinib.
Lumacaftor
Moderate
The metabolism of Larotrectinib can be increased when combined with Lumacaftor.
Apalutamide
Unknown severity
The serum concentration of Larotrectinib can be decreased when it is combined with Apalutamide.
Pitolisant
Unknown severity
The serum concentration of Larotrectinib can be decreased when it is combined with Pitolisant.
Isavuconazole
Moderate
The metabolism of Larotrectinib can be decreased when combined with Isavuconazole.
Isavuconazonium
Moderate
The metabolism of Larotrectinib can be decreased when combined with Isavuconazonium.
Fluconazole
Moderate
The metabolism of Larotrectinib can be decreased when combined with Fluconazole.
Erythromycin
Unknown severity
The serum concentration of Larotrectinib can be increased when it is combined with Erythromycin.
The metabolism of Larotrectinib can be decreased when combined with Verapamil.
Simeprevir
Moderate
The metabolism of Larotrectinib can be decreased when combined with Simeprevir.
The serum concentration of Larotrectinib can be increased when it is combined with Ivacaftor.
Linagliptin
Moderate
The metabolism of Larotrectinib can be decreased when combined with Linagliptin.
Netupitant
Moderate
The metabolism of Larotrectinib can be decreased when combined with Netupitant.
Venetoclax
Moderate
The metabolism of Larotrectinib can be decreased when combined with Venetoclax.
Ivosidenib
Moderate
The metabolism of Larotrectinib can be increased when combined with Ivosidenib.
Dronedarone
Moderate
The metabolism of Larotrectinib can be decreased when combined with Dronedarone.
Fedratinib
Unknown severity
The serum concentration of Larotrectinib can be increased when it is combined with Fedratinib.
Levoketoconazole
Moderate
The metabolism of Larotrectinib can be decreased when combined with Levoketoconazole.
Metreleptin
Moderate
The metabolism of Larotrectinib can be increased when combined with Metreleptin.
Dabrafenib
Unknown severity
The serum concentration of Larotrectinib can be decreased when it is combined with Dabrafenib.
Cyclosporine
Moderate
The metabolism of Larotrectinib can be decreased when combined with Cyclosporine.
Berotralstat
Moderate
The metabolism of Larotrectinib can be decreased when combined with Berotralstat.
The serum concentration of Avanafil can be increased when it is combined with Larotrectinib.
Salmon calcitonin
Moderate
The therapeutic efficacy of Salmon calcitonin can be decreased when used in combination with Larotrectinib.
Thyrotropin alfa
Moderate
The therapeutic efficacy of Thyrotropin alfa can be decreased when used in combination with Larotrectinib.
Follitropin
Moderate
The therapeutic efficacy of Follitropin can be decreased when used in combination with Larotrectinib.
Liothyronine
Moderate
The therapeutic efficacy of Liothyronine can be decreased when used in combination with Larotrectinib.
Carbimazole
Moderate
The therapeutic efficacy of Carbimazole can be decreased when used in combination with Larotrectinib.
Propylthiouracil
Moderate
The therapeutic efficacy of Propylthiouracil can be decreased when used in combination with Larotrectinib.
The therapeutic efficacy of Liotrix can be decreased when used in combination with Larotrectinib.
3,5-Diiodotyrosine
Moderate
The therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Larotrectinib.
Tiratricol
Moderate
The therapeutic efficacy of Tiratricol can be decreased when used in combination with Larotrectinib.
Parathyroid hormone
Moderate
The therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Larotrectinib.
Teriparatide
Moderate
The therapeutic efficacy of Teriparatide can be decreased when used in combination with Larotrectinib.
Potassium Iodide
Moderate
The therapeutic efficacy of Potassium Iodide can be decreased when used in combination with Larotrectinib.
Dibromotyrosine
Moderate
The therapeutic efficacy of Dibromotyrosine can be decreased when used in combination with Larotrectinib.
Thyroid, porcine
Moderate
The therapeutic efficacy of Thyroid, porcine can be decreased when used in combination with Larotrectinib.
Potassium perchlorate
Moderate
The therapeutic efficacy of Potassium perchlorate can be decreased when used in combination with Larotrectinib.
Protirelin
Moderate
The therapeutic efficacy of Protirelin can be decreased when used in combination with Larotrectinib.
The therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Larotrectinib.
Methylthiouracil
Moderate
The therapeutic efficacy of Methylthiouracil can be decreased when used in combination with Larotrectinib.
The therapeutic efficacy of Elcatonin can be decreased when used in combination with Larotrectinib.
Benzylthiouracil
Moderate
The therapeutic efficacy of Benzylthiouracil can be decreased when used in combination with Larotrectinib.
Thyrotropin
Moderate
The therapeutic efficacy of Thyrotropin can be decreased when used in combination with Larotrectinib.
Levothyroxine
Moderate
The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Larotrectinib.
Cenobamate
Unknown severity
The serum concentration of Larotrectinib can be decreased when it is combined with Cenobamate.
The serum concentration of Larotrectinib can be increased when it is combined with Ritonavir.
Haloperidol
Unknown severity
The serum concentration of Haloperidol can be increased when it is combined with Larotrectinib.
The metabolism of Tucatinib can be decreased when combined with Larotrectinib.
Showing 50 of 171 interactions
Food & lifestyle interactions
Avoid Grapefruit
Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of larotrectinib.
Advice
Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of larotrectinib.
Advice
Take with or without food.
Toxicity & overdose
Although there is no available data on larotrectinib use in pregnant women, based on literature reports in human subjects with congenital mutations leading to changes in TRK signaling, findings from animal studies, and the agent's mechanism of action it is believed that larotrectinib can cause embryo-fetal harm when administered to a pregnant woman.
[L49816]
Published reports of individuals with congenital mutations in TRK pathway proteins suggest that decreases in TRK-mediated signaling are correlated with obesity, developmental delays, cognitive impairment, insensitivity to pain, and anhidrosis.
[L49816]
Furthermore, animal studies have revealed that lacrotrectinib can cross the placenta.
[L49816]
Advise pregnant women of the potential risk to a fetus.
[L49816]
Female patients of reproductive potential who are being treated with larotrectinib are advised to use effective contraception during larotrectinib treatment and for at least one week after the final dose.
[L49816]
Males with female partners of reproductive potential are also advised to use effective contraception during larotrectinib therapy and for one week after the final dose.
[L49816]
Carcinogenicity studies have not been conducted with larotrectinib.
[L49816]
Larotrectinib was not mutagenic in the in vitro bacterial reverse mutation (Ames) assays, with or without metabolic activation, or in the in vitro mammalian mutagenesis assays, with or without metabolic activation.
[L49816]
In vivo, larotrectinib was negative in the mouse micronucleus test.
[L49816]
[L49816]
Published reports of individuals with congenital mutations in TRK pathway proteins suggest that decreases in TRK-mediated signaling are correlated with obesity, developmental delays, cognitive impairment, insensitivity to pain, and anhidrosis.
[L49816]
Furthermore, animal studies have revealed that lacrotrectinib can cross the placenta.
[L49816]
Advise pregnant women of the potential risk to a fetus.
[L49816]
Female patients of reproductive potential who are being treated with larotrectinib are advised to use effective contraception during larotrectinib treatment and for at least one week after the final dose.
[L49816]
Males with female partners of reproductive potential are also advised to use effective contraception during larotrectinib therapy and for one week after the final dose.
[L49816]
Carcinogenicity studies have not been conducted with larotrectinib.
[L49816]
Larotrectinib was not mutagenic in the in vitro bacterial reverse mutation (Ames) assays, with or without metabolic activation, or in the in vitro mammalian mutagenesis assays, with or without metabolic activation.
[L49816]
In vivo, larotrectinib was negative in the mouse micronucleus test.
[L49816]
How it works
Mechanism of action
Tropomysoin receptor kinases (TRK) like TRKA, TRKB, and TRKC elicit activities that regulate the natural growth, differentiation, and survival of neurons when they interact with endogenous neutrotrophin ligands.[A40035][A40037][A40038][A40046][A40047] TRKA, TRKB, and TRKC are themselves encoded by the NTRK1, NTRK2, and NTRK3 genes, respectively.[A40035][A40037][A40038][A40046][A40047] It has been discovered that chromosomal rearrangements involving in-frame fusions of these genes with various partners, translocations in the TRK kinase domains, mutations in the TRK ligand-binding site, amplifications of NTRK, or the expression of TRK splice variants can result in constitutively-activated chimeric TRK fusion proteins that can act as oncogenic drivers that promote cell proliferation and survival in tumor cell lines.[A40035][A40037][A40038][A40046][A40047][L49816]
Subsequently, larotrectinib functions as an inhibitor of TRKs including TRKA, B, and C.[A40035][A40037][A40038][A40046][A40047][L49816] In in vitro and in vivo tumor models, larotrectinib demonstrated anti-tumor activity in cells with constitutive activation of TRK proteins resulting from gene fusions, deletion of a protein regulatory domain, or in cells with TRK protein overexpression.[A40035][A40037][A40038][A40046][A40047][L49816] Larotrectinib had minimal activity in cell lines with point mutations in the TRKA kinase domain, including the clinically identified acquired resistance mutation, G595R.[L49816] Point mutations in the TRKC kinase domain with clinically identified acquired resistance to larotrectinib include G623R, G696A, and F617L.[L49816]
Subsequently, larotrectinib functions as an inhibitor of TRKs including TRKA, B, and C.[A40035][A40037][A40038][A40046][A40047][L49816] In in vitro and in vivo tumor models, larotrectinib demonstrated anti-tumor activity in cells with constitutive activation of TRK proteins resulting from gene fusions, deletion of a protein regulatory domain, or in cells with TRK protein overexpression.[A40035][A40037][A40038][A40046][A40047][L49816] Larotrectinib had minimal activity in cell lines with point mutations in the TRKA kinase domain, including the clinically identified acquired resistance mutation, G595R.[L49816] Point mutations in the TRKC kinase domain with clinically identified acquired resistance to larotrectinib include G623R, G696A, and F617L.[L49816]
Pharmacodynamics
In a broad panel of purified enzyme assays, larotrectinib inhibited TRKA, TRKB, and TRKC with IC50 values between 5-11 nM.[L49816] One other kinase, TNK2, was inhibited at approximately 100-fold higher concentration.[L49816] At doses that are nine-fold greater than the recommended adult dose, larotrectinib does not elicit any QTc interval prolongation that is clinically relevant.[L49816] No dose adjustment is recommended for patients with renal impairment of any severity,[L49816] but dose reductions are warranted in patients with moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment.[L49816]
Pharmacokinetics
How the body processes this drug — absorption, distribution, metabolism, and elimination
Absorption
The mean absolute bioavailability of larotrectinib capsules is approximately 34% (range: 32-37%).
[L49816]
In adult patients who received larotrectinib capsules 100 mg twice daily, Cmax was achieved at about one hour after dosing and steady-state was reached within three days.
[L49816]
The mean steady-state Cmax and AUC0-24h of larotrectinib capsules was 788 ng/mL and 4351 ng*h/mL, respectively.
[L49816]
In healthy subjects, the AUC of the larotrectinib oral solution was similar to that of the capsules and the Cmax was 36% greater with the oral solution.
[L49816]
As compared to a fasted state, the administration of larotrectinib in healthy subjects alongside a high-fat meal resulted in a similar AUC and a reduction in Cmax of 35%.
[L49816]
[L49816]
In adult patients who received larotrectinib capsules 100 mg twice daily, Cmax was achieved at about one hour after dosing and steady-state was reached within three days.
[L49816]
The mean steady-state Cmax and AUC0-24h of larotrectinib capsules was 788 ng/mL and 4351 ng*h/mL, respectively.
[L49816]
In healthy subjects, the AUC of the larotrectinib oral solution was similar to that of the capsules and the Cmax was 36% greater with the oral solution.
[L49816]
As compared to a fasted state, the administration of larotrectinib in healthy subjects alongside a high-fat meal resulted in a similar AUC and a reduction in Cmax of 35%.
[L49816]
Half-life
In healthy subjects, the half-life of larotrectinib following oral administration is 2.9 hours.
[L49816]
[L49816]
Protein binding
Larotrectinib is 70% bound to human plasma proteins in vitro and binding is independent of drug concentration.
[L49816]
The blood-to-plasma concentration ratio is 0.9.
[L49816]
[L49816]
The blood-to-plasma concentration ratio is 0.9.
[L49816]
Volume of distribution
Following intravenous administration to healthy subjects, the mean volume of distribution of larotrectinib at steady-state was approximately 48L.
[L49816]
[L49816]
Metabolism
Larotrectinib is metabolized predominantly by CYP3A4.
[L49816]
Following oral administration of a single 100 mg dose of radiolabeled larotrectinib in healthy subjects, the major circulating drug components in plasma were unchanged larotrectinib (19%) and an O-linked glucuronide (26%).
[L49816]
[L49816]
Following oral administration of a single 100 mg dose of radiolabeled larotrectinib in healthy subjects, the major circulating drug components in plasma were unchanged larotrectinib (19%) and an O-linked glucuronide (26%).
[L49816]
Route of elimination
Following oral administration of a single 100 mg dose of radiolabeled larotrectinib in healthy subjects, 58% (5% unchanged) of the administered radioactivity was recovered in feces and 39% (20% unchanged) was recovered in urine.
[L49816]
[L49816]
Clearance
The mean clearance CL/F of larotrectinib is 98 L/h.
[L49816]
[L49816]
Drug targets(3)
Proteins and enzymes this drug interacts with in the body
BDNF/NT-3 growth factors receptor
NTRK2
inhibitor
Specific functionATP binding
Cellular location
Cell membrane
General function & pharmacology
Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity (By similarity). Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2 .
PMID:15494731 PMID:7574684
Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation .
PMID:15494731
Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades.
Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity.
Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions.
May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia
PMID:15494731 PMID:7574684
Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation .
PMID:15494731
Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades.
Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity.
Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions.
May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia
NT-3 growth factor receptor
NTRK3
inhibitor
Specific functionATP binding
Cellular location
Membrane
General function & pharmacology
Receptor tyrosine kinase involved in nervous system and probably heart development. Upon binding of its ligand NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different signaling pathways, including the phosphatidylinositol 3-kinase/AKT and the MAPK pathways, that control cell survival and differentiation
High affinity nerve growth factor receptor
NTRK1
inhibitor
Specific functionATP binding
Cellular location
Cell membrane
General function & pharmacology
Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand .
PMID:1281417 PMID:15488758 PMID:17196528 PMID:1849459 PMID:1850821 PMID:22649032 PMID:27445338 PMID:8325889
Can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival (By similarity).
Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation .
PMID:1281417
Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival.
Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors
PMID:1281417 PMID:15488758 PMID:17196528 PMID:1849459 PMID:1850821 PMID:22649032 PMID:27445338 PMID:8325889
Can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival (By similarity).
Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation .
PMID:1281417
Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival.
Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors
Metabolizing enzymes(1)
Enzymes involved in drug metabolism — important for understanding drug interactions
Enzyme activity key
substrate
inhibitor
inducer
CYP3A4Cytochrome P450 3A4
substrate
Transporters(2)
Proteins that transport this drug across cell membranes
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
Broad substrate specificity ATP-binding cassette transporter ABCG2
ABCG2
substrate
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
Scientific references(5)
Berger S., Martens U.M., Bochum S.
Larotrectinib (LOXO-101).
Recent Results Cancer Research
2018211:141-151. doi: 10.1007/978-3-319-91442-8_10
Drilon A., Nagasubramanian R., Blake J.F., Ku N., Tuch B.B., Ebata K., Smith S., Lauriault V., Kolakowski G.R., Brandhuber B.J., Larsen P.D., Bouhana K.S., Winski S.L., Hamor R., Wu W.I., Parker A., Morales T.H., Sullivan F.X., DeWolf W.E., Wollenberg L.A., Gordon P.R., Douglas-Lindsay D.N., Scaltriti M., Benayed R., Raj S., Hanusch B., Schram A.M., Jonsson P., Berger M.F., Hechtman J.F., Taylor B.S., Andrews S., Rothenberg S.M., Hyman D.M.
A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion-Positive Solid Tumors.
Cancer Discov
2017 Sep7(9):963-972. doi: 10.1158/2159-8290.CD-17-0507. Epub 2017 Jun 3
Fuse M.J., Okada K., Oh-Hara T., Ogura H., Fujita N., Katayama R.
Mechanisms of Resistance to NTRK Inhibitors and Therapeutic Strategies in NTRK1-Rearranged Cancers.
Molecular Cancer Therapeutics
2017 Oct16(10):2130-2143. doi: 10.1158/1535-7163.MCT-16-0909. Epub 2017 Jul 27
Doebele R.C., Davis L.E., Vaishnavi A., Le A.T., Estrada-Bernal A., Keysar S., Jimeno A., Varella-Garcia M., Aisner D.L., Li Y., Stephens P.J., Morosini D., Tuch B.B., Fernandes M., Nanda N., Low J.A.
An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101.
Cancer Discov
2015 Oct5(10):1049-57. doi: 10.1158/2159-8290.CD-15-0443. Epub 2015 Jul 27
Vaishnavi A., Le A.T., Doebele R.C.
TRKing down an old oncogene in a new era of targeted therapy.
Cancer Discov
2015 Jan5(1):25-34. doi: 10.1158/2159-8290.CD-14-0765. Epub 2014 Dec 19
ATC classification(1 code)
ATC L01EX12
Affected organisms(1)
Humans
Salt forms(1)
Larotrectinib sulfate(DBSALT002820)
Commercial products(14)
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)
Larotrectinib
Additional database identifiers
Drugs Product Database (DPD)
23320
ChemSpider
44210503
BindingDB
136597
ZINC
ZINC000118399834
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8032
GeneCards
NTRK2
GenBank Gene Database
U12140
GenBank Protein Database
530791
Guide to Pharmacology
1818
UniProt Accession
NTRK2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8033
GeneCards
NTRK3
Guide to Pharmacology
1819
UniProt Accession
NTRK3_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8031
GenAtlas
NTRK1
GeneCards
NTRK1
GenBank Gene Database
M23102
GenBank Protein Database
339918
Guide to Pharmacology
1817
UniProt Accession
NTRK1_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: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
Patent information
20 active patents
11337967
United States
Approved 16 May 2017 · Expires 16 May 2037
11y 1m
11974998
United States
Approved 16 May 2017 · Expires 16 May 2037
11y 1m
10045991
United States
Approved 14 Aug 2018 · Expires 4 Apr 2037
11 years
10137127
United States
Approved 27 Nov 2018 · Expires 4 Apr 2037
11 years
10668072
United States
Approved 2 Jun 2020 · Expires 4 Apr 2037
11 years
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 about 1 month ago(4 Mar 2026)