Larotrectinib

Identification

Summary

Larotrectinib is a kinase inhibitor used to treat solid tumors with neurotrophic receptor tyrosine kinase gene fusion, are metastatic, high risk for surgery, or have no alternative treatments.

Brand Names
Vitrakvi
Generic Name
Larotrectinib
DrugBank Accession Number
DB14723
Background

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.8 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.8

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.6

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 428.444
Monoisotopic: 428.177230298
Chemical Formula
C21H22F2N6O2
Synonyms
  • Larotrectinib
External IDs
  • ARRY 470
  • ARRY-470
  • LOXO 101
  • LOXO-101

Pharmacology

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.7

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.7

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofNtrk1 fusion positive•••••••••••••••••• ••••••••••••••••• ••••••••
Treatment ofNtrk1 fusion positive•••••••••••••••••• ••••••••••••••••• ••••••••
Treatment ofNtrk1 fusion positive•••••••••••••••••• ••••••••••••••••• ••••••••
Treatment ofNtrk1 fusion positive•••••••••••••••••• ••••••••••••••••• ••••••••
Treatment ofNtrk2 fusion positive•••••••••••••••••• ••••••••••••••••• ••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

In a broad panel of purified enzyme assays, larotrectinib inhibited TRKA, TRKB, and TRKC with IC50 values between 5-11 nM.7 One other kinase, TNK2, was inhibited at approximately 100-fold higher concentration.7 At doses that are nine-fold greater than the recommended adult dose, larotrectinib does not elicit any QTc interval prolongation that is clinically relevant.7 No dose adjustment is recommended for patients with renal impairment of any severity,7 but dose reductions are warranted in patients with moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment.7

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.1,2,3,4,5 TRKA, TRKB, and TRKC are themselves encoded by the NTRK1, NTRK2, and NTRK3 genes, respectively.1,2,3,4,5 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.1,2,3,4,5,7

Subsequently, larotrectinib functions as an inhibitor of TRKs including TRKA, B, and C.1,2,3,4,5,7 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.1,2,3,4,5,7 Larotrectinib had minimal activity in cell lines with point mutations in the TRKA kinase domain, including the clinically identified acquired resistance mutation, G595R.7 Point mutations in the TRKC kinase domain with clinically identified acquired resistance to larotrectinib include G623R, G696A, and F617L.7

TargetActionsOrganism
AHigh affinity nerve growth factor receptor
inhibitor
Humans
ABDNF/NT-3 growth factors receptor
inhibitor
Humans
ANT-3 growth factor receptor
inhibitor
Humans
Absorption

The mean absolute bioavailability of larotrectinib capsules is approximately 34% (range: 32-37%).7 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.7 The mean steady-state Cmax and AUC0-24h of larotrectinib capsules was 788 ng/mL and 4351 ng*h/mL, respectively.7 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.7

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%.7

Volume of distribution

Following intravenous administration to healthy subjects, the mean volume of distribution of larotrectinib at steady-state was approximately 48L.7

Protein binding

Larotrectinib is 70% bound to human plasma proteins in vitro and binding is independent of drug concentration.7 The blood-to-plasma concentration ratio is 0.9.7

Metabolism

Larotrectinib is metabolized predominantly by CYP3A4.7 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%).7

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.7

Half-life

In healthy subjects, the half-life of larotrectinib following oral administration is 2.9 hours.7

Clearance

The mean clearance CL/F of larotrectinib is 98 L/h.7

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

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.7 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.7 Furthermore, animal studies have revealed that lacrotrectinib can cross the placenta.7 Advise pregnant women of the potential risk to a fetus.7

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.7 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.7

Carcinogenicity studies have not been conducted with larotrectinib.7 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.7 In vivo, larotrectinib was negative in the mouse micronucleus test.7

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Larotrectinib can be increased when it is combined with Abametapir.
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Larotrectinib.
AmbroxolThe risk or severity of methemoglobinemia can be increased when Larotrectinib is combined with Ambroxol.
AmiodaroneThe metabolism of Larotrectinib can be decreased when combined with Amiodarone.
AmprenavirThe metabolism of Larotrectinib can be decreased when combined with Amprenavir.
Food Interactions
  • Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of larotrectinib.
  • Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of larotrectinib.
  • Take with or without food.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Larotrectinib sulfateRDF76R62ID1223405-08-0PXHANKVTFWSDSG-QLOBERJESA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
VitrakviSolution, concentrate20 mg/1mLOropharyngealBayer HealthCare Pharmaceuticals Inc.2019-07-26Not applicableUS flag
VitrakviCapsule25 mg/1OralLoxo Oncology, Inc.2018-11-26Not applicableUS flag
VitrakviSolution20 mg/1mLOralLoxo Oncology, Inc.2018-11-26Not applicableUS flag
VitrakviSolution20 mg/mlOralBayer Ag2021-05-25Not applicableEU flag
VitrakviCapsule25 mgOralBayer Ag2020-12-16Not applicableEU flag

Categories

ATC Codes
L01EX12 — Larotrectinib
Drug Categories
Classification
Not classified
Affected organisms
  • Humans

Chemical Identifiers

UNII
PF9462I9HX
CAS number
1223403-58-4
InChI Key
NYNZQNWKBKUAII-KBXCAEBGSA-N
InChI
InChI=1S/C21H22F2N6O2/c22-13-3-4-16(23)15(10-13)18-2-1-7-28(18)19-6-9-29-20(26-19)17(11-24-29)25-21(31)27-8-5-14(30)12-27/h3-4,6,9-11,14,18,30H,1-2,5,7-8,12H2,(H,25,31)/t14-,18+/m0/s1
IUPAC Name
(3S)-N-{5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl}-3-hydroxypyrrolidine-1-carboxamide
SMILES
O[C@H]1CCN(C1)C(=O)NC1=C2N=C(C=CN2N=C1)N1CCC[C@@H]1C1=C(F)C=CC(F)=C1

References

General References
  1. Berger S, Martens UM, Bochum S: Larotrectinib (LOXO-101). Recent Results Cancer Res. 2018;211:141-151. doi: 10.1007/978-3-319-91442-8_10. [Article]
  2. Drilon A, Nagasubramanian R, Blake JF, Ku N, Tuch BB, Ebata K, Smith S, Lauriault V, Kolakowski GR, Brandhuber BJ, Larsen PD, Bouhana KS, Winski SL, Hamor R, Wu WI, Parker A, Morales TH, Sullivan FX, DeWolf WE, Wollenberg LA, Gordon PR, Douglas-Lindsay DN, Scaltriti M, Benayed R, Raj S, Hanusch B, Schram AM, Jonsson P, Berger MF, Hechtman JF, Taylor BS, Andrews S, Rothenberg SM, Hyman DM: 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 Sep;7(9):963-972. doi: 10.1158/2159-8290.CD-17-0507. Epub 2017 Jun 3. [Article]
  3. Fuse MJ, Okada K, Oh-Hara T, Ogura H, Fujita N, Katayama R: Mechanisms of Resistance to NTRK Inhibitors and Therapeutic Strategies in NTRK1-Rearranged Cancers. Mol Cancer Ther. 2017 Oct;16(10):2130-2143. doi: 10.1158/1535-7163.MCT-16-0909. Epub 2017 Jul 27. [Article]
  4. Doebele RC, Davis LE, Vaishnavi A, Le AT, Estrada-Bernal A, Keysar S, Jimeno A, Varella-Garcia M, Aisner DL, Li Y, Stephens PJ, Morosini D, Tuch BB, Fernandes M, Nanda N, Low JA: An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101. Cancer Discov. 2015 Oct;5(10):1049-57. doi: 10.1158/2159-8290.CD-15-0443. Epub 2015 Jul 27. [Article]
  5. Vaishnavi A, Le AT, Doebele RC: TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov. 2015 Jan;5(1):25-34. doi: 10.1158/2159-8290.CD-14-0765. Epub 2014 Dec 19. [Article]
  6. Larotrectinib FDA Approval Press Release [Link]
  7. FDA Approved Drug Products: Vitrakvi (larotrectinib) capsules or solution for oral administration (November 2023) [Link]
  8. National Cancer Institute (NCI) Drug Dictionary: Larotrectinib sulfate [Link]
Human Metabolome Database
HMDB0304896
ChemSpider
44210503
BindingDB
136597
RxNav
2105628
ChEMBL
CHEMBL3889654
ZINC
ZINC000118399834
Wikipedia
Larotrectinib
FDA label
Download (528 KB)
MSDS
Download (200 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Active Not RecruitingScreeningAdvanced Lymphomas / Advanced Malignant Solid Tumor / Bladder Carcinoma / Breast Carcinoma / Carcinoma of the Head and Neck / Carcinoma of the Skin / Cervical Carcinoma / Colon Carcinoma / Colorectal Carcinoma (CRC) / Endometrial Carcinoma / Esophageal Carcinoma / Gastric Carcinoma / Glioma / Hematopoietic and Lymphoid System Neoplasm / Liver and Intrahepatic Bile Duct Carcinoma / Lung Carcinoma / Lymphoma / Malignant Uterine Neoplasm / Melanoma / Multiple Myeloma (MM) / Ovarian Carcinoma / Pancreatic Carcinoma / Prostate Carcinoma / Rectal Carcinoma / Recurrent Bladder Carcinoma / Recurrent Breast Carcinoma / Recurrent Cervical Carcinoma / Recurrent Colon Carcinoma / Recurrent Colorectal Carcinoma / Recurrent Esophageal Carcinoma / Recurrent Gastric Carcinoma / Recurrent Gliomas / Recurrent Head and Neck Carcinoma / Recurrent Liver Carcinoma / Recurrent Lung Carcinoma / Recurrent Lymphoma / Recurrent Malignant Solid Neoplasm / Recurrent Melanoma / Recurrent multiple myeloma / Recurrent Ovarian Carcinoma / Recurrent Pancreatic Carcinoma / Recurrent Prostate Carcinoma / Recurrent Rectal Carcinoma / Recurrent Skin Carcinoma / Recurrent Thyroid Gland Carcinoma / Recurrent Uterine Corpus Cancer / Refractory Lymphomas / Refractory Malignant Solid Neoplasm / Refractory Multiple Myeloma / Renal Carcinoma / Thyroid Gland Carcinoma / Uterine Corpus Cancer1
2Active Not RecruitingTreatmentAdvanced Malignant Solid Tumor / Ependymoma, Recurrent / Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Recurrent Gliomas / Recurrent Hepatoblastoma / Recurrent Kidney Wilms Tumor / Recurrent Langerhans Cell Histiocytosis / Recurrent Malignant Germ Cell Tumor / Recurrent Malignant Gliomas / Recurrent Malignant Solid Neoplasm / Recurrent Medulloblastoma / Recurrent Neuroblastoma / Recurrent Non-Hodgkin Lymphoma / Recurrent Osteosarcoma / Recurrent Rhabdoid Tumor / Recurrent Rhabdomyosarcoma / Recurrent Soft Tissue Sarcoma / Refractory Ependymoma / Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Refractory Glioma / Refractory Hepatoblastoma / Refractory Langerhans cell histiocytosis / Refractory Malignant Germ Cell Tumor / Refractory Malignant Glioma / Refractory Malignant Solid Neoplasm / Refractory Medulloblastoma / Refractory Neuroblastoma / Refractory Non-Hodgkin's lymphoma / Refractory Osteosarcoma / Refractory Rhabdoid Tumor / Refractory Rhabdomyosarcoma / Refractory Soft Tissue Sarcomas / Refractory, primary Central Nervous System Neoplasm1
2Active Not RecruitingTreatmentCentral Nervous System Neoplasm / Infantile Fibrosarcoma / Recurrent Acute Leukemia / Refractory Acute Leukemia / Solid Tumors1
2Active Not RecruitingTreatmentSolid Tumors Harboring NTRK Fusion1
2RecruitingScreeningAdvanced Malignant Solid Tumor / Ann Arbor Stage III Non-Hodgkin Lymphoma / Ann Arbor Stage IV Non-Hodgkin Lymphoma / Ependymoma, Recurrent / Histiocytic Sarcoma (HS) / Juvenile Xanthogranuloma (JXG) / Langerhans Cell Histiocytosis (LCH) / Malignant Glioma / Recurrent Childhood Rhabdomyosarcoma / Recurrent Ewing's Sarcoma / Recurrent Gliomas / Recurrent Hepatoblastoma / Recurrent Langerhans Cell Histiocytosis / Recurrent Malignant Germ Cell Tumor / Recurrent Malignant Solid Neoplasm / Recurrent Medulloblastoma / Recurrent Neuroblastoma / Recurrent Non-Hodgkin Lymphoma / Recurrent Osteosarcoma / Recurrent Peripheral Primitive Neuroectodermal Tumor / Recurrent Primary Central Nervous System Neoplasm / Recurrent Rhabdoid Tumor / Recurrent Soft Tissue Sarcoma / Refractory Ewing Sarcoma / Refractory Glioma / Refractory Hepatoblastoma / Refractory Langerhans cell histiocytosis / Refractory Malignant Germ Cell Tumor / Refractory Malignant Solid Neoplasm / Refractory Medulloblastoma / Refractory Neuroblastoma / Refractory Non-Hodgkin's lymphoma / Refractory Osteosarcoma / Refractory Peripheral Primitive Neuroectodermal Tumor / Refractory Rhabdoid Tumor / Refractory Rhabdomyosarcoma / Refractory, primary Central Nervous System Neoplasm / Rhabdoid Tumors / Stage III Osteosarcoma AJCC v7 / Stage III Soft Tissue Sarcoma AJCC v7 / Stage IV Osteosarcoma AJCC v7 / Stage IV Soft Tissue Sarcoma AJCC v7 / Stage IVA Osteosarcoma AJCC v7 / Stage IVB Osteosarcoma AJCC v7 / Wilms' tumor1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral100 mg
CapsuleOral100 mg/1
CapsuleOral25 mg
CapsuleOral25 mg/1
SolutionOral20 mg / mL
SolutionOral20 mg/1mL
SolutionOral20 MG/ML
Solution, concentrateOropharyngeal20 mg/1mL
SolutionOral20 mg
Capsule, coatedOral100 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US10045991No2018-08-142037-04-04US flag
US10047097No2018-08-142029-10-21US flag
US9782414No2017-10-102035-11-16US flag
US8865698No2014-10-212029-10-21US flag
US9447104No2016-09-202029-10-21US flag
US10005783No2018-06-262029-10-21US flag
US9676783No2017-06-132029-10-21US flag
US8513263No2013-08-202029-12-23US flag
US9127013No2015-09-082029-10-21US flag
US10137127No2018-11-272037-04-04US flag
US10285993No2019-05-142035-11-16US flag
US10172861No2019-01-082035-11-16US flag
US10774085No2020-09-152029-10-21US flag
US10668072No2020-06-022037-04-04US flag
US10813936No2020-10-272035-11-16US flag
US10799505No2020-10-132036-08-15US flag
US11191766No2021-12-072037-04-04US flag
US11484535No2017-04-042037-04-04US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.238 mg/mLALOGPS
logP2.07ALOGPS
logP2.44Chemaxon
logS-3.3ALOGPS
pKa (Strongest Acidic)10.94Chemaxon
pKa (Strongest Basic)0.7Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area86 Å2Chemaxon
Rotatable Bond Count3Chemaxon
Refractivity122.96 m3·mol-1Chemaxon
Polarizability41.61 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0001900000-a714cdeef7c9e70af1ca
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-1002900000-c230a7e2d2437bb9b32c
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0004900000-f3692f022953e93b90f3
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-01t9-2025900000-f86bb8c4e561dfe77532
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-017j-1469400000-07acdbee59e41f7d8145
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-1489100000-b2d140f3ada85e073f32
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
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 sympatheti...
Gene Name
NTRK1
Uniprot ID
P04629
Uniprot Name
High affinity nerve growth factor receptor
Molecular Weight
87496.465 Da
References
  1. FDA Approved Drug Products: Vitrakvi (larotrectinib) capsules or solution for oral administration (November 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein homodimerization activity
Specific Function
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, differenti...
Gene Name
NTRK2
Uniprot ID
Q16620
Uniprot Name
BDNF/NT-3 growth factors receptor
Molecular Weight
91998.175 Da
References
  1. FDA Approved Drug Products: Vitrakvi (larotrectinib) capsules or solution for oral administration (November 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
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.
Specific Function
Atp binding
Gene Name
NTRK3
Uniprot ID
Q16288
Uniprot Name
NT-3 growth factor receptor
Molecular Weight
94427.47 Da
References
  1. FDA Approved Drug Products: Vitrakvi (larotrectinib) capsules or solution for oral administration (November 2023) [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. FDA Approved Drug Products: Vitrakvi (larotrectinib) capsules or solution for oral administration (November 2023) [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. FDA Approved Drug Products: Vitrakvi (larotrectinib) capsules or solution for oral administration (November 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. FDA Approved Drug Products: Vitrakvi (larotrectinib) capsules or solution for oral administration (November 2023) [Link]

Drug created at November 29, 2018 17:47 / Updated at January 31, 2024 01:10