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 tropomyosin receptor kinase (Trk) inhibitor with demonstrated antineoplastic activity. 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. Trk, a receptor tyrosine kinase activated by neurotrophins, is mutated in a variety of cancer cell types and plays an important role in tumor cell growth and survival.

Originally discovered by Array BioPharma, the agent was ultimately licensed to Loxo Oncology in 2013. Larotrectinib is another example of innovative new cancer therapy medications that target key, specific genetic biomarker drivers of cancer rather than particular types of tumors 6.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
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 either 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, and c) have no satisfactory alternative treatments or that have progressed following treatment Label.

At the moment, these uses of larotrectinib are only approved under the auspices of an 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 Label.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

At doses that are nine-fold greater than the recommended adult dose, larotrectinib does not elicit any QTc interval prolongation that is clinically relevant Label.

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,Label.

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

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 has been recorded as 34%, from a range spanning 32% to 37% Label. In adult patients who received larotrectinib capsules 100 mg twice daily, peak plasma levels Cmax were achieved at about one hour after dosing and steady-state was reached within the time span of three days Label. The mean steady-state of these administered larotrectinib capsules was Cmax 788 ng/mL and the AUC(0-24hr) was 4351 ng*h/mL Label. Concurrently, in healthy subjects, the AUC of the administered larotrectinib oral solution formulation was similar to that of the capsules and the particular Cmax was 36% greater with the oral solution Label.

The AUC of larotrectinib was similar but the Cmax was reduced by 35% after oral administration of a single 100 mg capsule of larotrectinib to healthy subjects taken with a high-fat meal (approximately 900 calories, 58 grams carbohydrate, 56 grams fat and 43 grams protein) compared to the Cmax and AUC in the fasted state Label.

Volume of distribution

The mean volume of distribution Vss of larotrectinib has been documented as being 48L following intravenous administration in healthy subjects Label.

Protein binding

Larotrectinib is approximately 70% bound to human plasma proteins in vitro and binding is independent of drug concentrations Label. The blood to plasma concentration ratio is 0.9 Label.

Metabolism

Larotrectinib is metabolized predominantly by the CYP3A4 isoenzymes Label. Following oral administration of a single [14C] radiolabeled 100 mg dose of larotrectinib to healthy subjects, unchanged larotrectinib constituted 19% and an O-linked glucuronide constituted 26% of the major circulating radioactive drug components in plasma Label.

Route of elimination

Following oral administration of a single [14C] radiolabeled 100 mg dose of larotrectinib to healthy subjects, 58% (5% unchanged) of the administered radioactivity was recovered in feces and 39% (20% unchanged) was recovered in urine Label.

Half-life

The half-life of larotrectinib has been determined to be 2.9 hours Label.

Clearance

The mean clearance CL/F of larotrectinib has been documented as 98 L/h Label.

Adverse Effects
Adverseeffects
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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 Label. 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 Label. Furthermore, animal studies data note that lacrotrectinib can cross the placenta in animals Label. Advise pregnant women of the potential risk to a fetus Label.

There are no data on the presence of larotrectinib or its metabolites in human milk and no data on its effects on the breastfed child or on milk production Label. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with larotrectinib and for 1 week after the final dose Label.

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 Label. 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 Label.

Based on histopathological findings in the reproductive tracts of female rats in a 1-month repeated-dose study, larotrectinib use may reduce fertility in females Label.

The safety and effectiveness of larotrectinib in pediatric patients was established based upon data from clinical trials in adult or pediatric patients 28 days and older Label. The pharmacokinetics of larotrectinib in the pediatric population have also been determined to be similar to those seen in adults Label.

Clinical studies of larotrectinib did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects Label.

No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A). Larotrectinib clearance was reduced in subjects with moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment Label.

No dose adjustment is recommended for patients with renal impairment of any severity Label.

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

Fertility studies with larotrectinib have not been conducted. In a 3-month repeat-dose toxicity study in the rat, larotrectinib had no effects on spermatogenesis at 75 mg/kg/day (approximately 7 times the human exposure at the 100 mg twice daily dose) [FDA Label. Additionally, larotrectinib had no histological effects on the male reproductive tract in rats or monkeys at doses resulting in exposures up to 10 times the human exposure (AUC0-24hr) at the 100 mg twice daily clinical dose Label.

In a 1-month repeat-dose study in the rat, decreased uterine weight and uterine atrophy were seen at 200 mg/kg/day [approximately 45 times the human exposure (AUC) at the 100 mg twice daily dose] Label. Fewer corpora lutea and increased incidence of anestrus were also noted at doses ≥ 60 mg/kg/day (approximately 10 times the human exposure at the 100 mg twice daily dose] Label. There were no findings in female reproductive organs in repeat-dose studies in monkeys at exposures up to 22 times the human exposure at the 100 mg twice daily dose Label.

In a 1-month repeat-dose study in the rat, decreased uterine weight and uterine atrophy were seen at 200 mg/kg/day [approximately 45 times the human exposure (AUC) at the 100 mg twice daily dose] Label. Fewer corpora lutea and increased incidence of anestrus were also noted at doses ≥ 60 mg/kg/day (approximately 10 times the human exposure at the 100 mg twice daily dose) Label. Decreased fertility occurred in a juvenile animal study Label. There were no findings in female reproductive organs in repeat-dose studies in monkeys at exposures up to 22 times the human exposure at the 100 mg twice daily dose Label.

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
AbaloparatideThe therapeutic efficacy of Abaloparatide can be decreased when used in combination with Larotrectinib.
AbametapirThe serum concentration of Larotrectinib can be increased when it is combined with Abametapir.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Larotrectinib.
AbirateroneThe metabolism of Larotrectinib can be decreased when combined with Abiraterone.
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Larotrectinib.
AfatinibThe serum concentration of Larotrectinib can be increased when it is combined with Afatinib.
AmbrisentanThe serum concentration of Larotrectinib can be increased when it is combined with Ambrisentan.
AmiodaroneThe metabolism of Larotrectinib can be decreased when combined with Amiodarone.
AmprenavirThe metabolism of Larotrectinib can be decreased when combined with Amprenavir.
ApalutamideThe serum concentration of Larotrectinib can be decreased when it is combined with Apalutamide.
Interactions
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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

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Product Ingredients
IngredientUNIICASInChI Key
Larotrectinib sulfateRDF76R62ID1223405-08-0PXHANKVTFWSDSG-QLOBERJESA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
VitrakviCapsule100 mg/1OralLoxo Oncology, Inc.2018-11-26Not applicableUS flag
VitrakviCapsule25 mgOralBayer Ag2020-12-16Not applicableEU flag
VitrakviSolution20 mg/mlOralBayer Ag2020-12-16Not applicableEU flag
VitrakviCapsule25 mg/1OralBayer HealthCare Pharmaceuticals Inc.2019-07-26Not applicableUS flag
VitrakviCapsule25 mgOralBayer2020-11-13Not applicableCanada flag
VitrakviCapsule25 mg/1OralLoxo Oncology, Inc.2018-11-26Not applicableUS flag
VitrakviSolution, concentrate20 mg/1mLOropharyngealBayer HealthCare Pharmaceuticals Inc.2019-07-26Not applicableUS flag
VitrakviSolution20 mg / mLOralBayer2019-09-04Not applicableCanada flag
VitrakviSolution20 mg/1mLOralLoxo Oncology, Inc.2018-11-26Not applicableUS flag
VitrakviCapsule100 mgOralBayer Ag2020-12-16Not applicableEU flag

Categories

ATC Codes
L01XE53 — Larotrectinib
Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

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]
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
2RecruitingScreeningAdvanced Malignant Solid Neoplasm / Ann Arbor Stage III Non-Hodgkin Lymphoma / Ann Arbor Stage IV Non-Hodgkin Lymphoma / Ependymoma, Recurrent / Gliomas, Malignant / Histiocytic Sarcoma (HS) / Juvenile Xanthogranuloma (JXG) / Langerhans Cell Histiocytosis (LCH) / 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
2RecruitingTreatmentAdvanced Malignant Solid Neoplasm / Bladder Carcinoma / Breast Carcinoma / Carcinoma, Pancreatic / Cervical Carcinoma / Colon Carcinoma / Colorectal Carcinoma (CRC) / Endometrial Carcinoma / Esophageal Carcinoma / Gastric Carcinoma / Gliomas / Head and Neck Carcinoma / Liver and Intrahepatic Bile Duct Carcinoma / Lung, Carcinoma / Malignant Lymphomas / Malignant Melanoma of Skin / Malignant Uterine Neoplasm / Ovarian Carcinoma / Plasma Cell Myeloma / Prostate Cancer / 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 Ovarian Carcinoma / Recurrent Pancreatic Carcinoma / Recurrent Plasma Cell Myeloma / Recurrent Prostate Carcinoma / Recurrent Rectal Carcinoma / Recurrent Skin Carcinoma / Recurrent Thyroid Gland Carcinoma / Recurrent Uterine Corpus Cancer / Refractory Lymphomas / Refractory Malignant Solid Neoplasm / Refractory Plasma Cell Myeloma / Renal Carcinoma / Skin Carcinoma / Thyroid Gland Carcinoma / Uterine Corpus Cancer1
2RecruitingTreatmentAdvanced Malignant Solid Neoplasm / Ependymoma, Recurrent / Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Recurrent Gliomas / Recurrent Hepatoblastoma / 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 Neuroblastoma / Refractory Non-Hodgkin's lymphoma / Refractory Osteosarcoma / Refractory Rhabdoid Tumor / Refractory Rhabdomyosarcoma / Refractory, primary Central Nervous System Neoplasm / Wilms' tumor1
2RecruitingTreatmentCentral Nervous System Neoplasms / Infantile Fibrosarcoma / Recurrent Acute Leukemia / Refractory Acute Leukemia / Solid Neoplasms1
2RecruitingTreatmentLocally Advanced Malignant Solid Neoplasm / Metastatic Malignant Solid Neoplasm1
2RecruitingTreatmentMultiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL) / Solid Tumors, Advanced Solid Tumors1
2RecruitingTreatmentSolid Tumors Harboring NTRK Fusion1
1CompletedBasic ScienceSoft Tissue Sarcoma, Adult1
1CompletedTreatmentSolid Tumors Harboring NTRK Fusion1
1, 2RecruitingTreatmentSolid Tumors Harboring NTRK Fusion1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral100 mg/1
CapsuleOral100 MG
CapsuleOral25 MG
CapsuleOral25 mg/1
SolutionOral20 mg/1mL
SolutionOral20 MG/ML
SolutionOral20 mg / mL
Solution, concentrateOropharyngeal20 mg/1mL
SolutionOral20 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

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
Not Available

Targets

Drugtargets2
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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
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
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

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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

Drug created on November 29, 2018 17:47 / Updated on October 24, 2021 16:00