Identification
- Brand Names
- Rozlytrek
- Generic Name
- Entrectinib
- DrugBank Accession Number
- DB11986
- Background
Entrectinib is a tropomyosin receptor tyrosine kinase (TRK) TRKA, TRKB, TRKC, proto-oncogene tyrosine-protein kinase ROS1, and anaplastic lymphoma kinase (ALK) inhibitor.7 It was approved by the FDA in August 2019 for use in the treatment of ROS1-positive metastatic non-small cell lung cancer and NTRK gene fusion positive solid tumors.9 Entrectinib's approved use is meant as a last line of therapy due to its accelerated approval based on early trial data. This therapy offers benefit over similar ALK inhibitors such as alectinib, ceritinib, and lorlatinib due to a wider range of targets.6
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Entrectinib (DB11986)
- Weight
- Average: 560.65
Monoisotopic: 560.271130685 - Chemical Formula
- C31H34F2N6O2
- Synonyms
- Entrectinib
- N-[5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl]-4-(4-methylpiperazin-1-yl)-2-(oxan-4-ylamino)benzamide
- External IDs
- RXDX-101
Pharmacology
- Indication
Entrectinib is indicated for the treatment of metastatic ROS1-positive non-small cell lung cancer in adults.7 Entrectinib is also indicated in adults and children over 12 years old for the treatment of NTRK gene fusion-positive solid tumors which have metastasized or for which surgical resection is likely to result in severe morbidity and for which has progressed on previous therapies or for which no comparable alternative therapies are available.
FoundationOne®Liquid CDx is the only FDA-approved test for the detection of ROS1 rearrangement(s) in NSCLC for selecting patients for treatment with entrectinib.10
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Metastatic non-small cell lung cancer •••••••••••• ••••• ••••••• Treatment of Solid metastatic tumor •••••••••••• ••••••••••• •••••• ••••••••• •• ••••• •••••••• •••••••••• ••••••••• •••••••• ••••••••• •••••••••• ••••••• Treatment of Solid metastatic tumor •••••••••••• ••••••••••• •••••• ••••••••• •• ••••• •••••••• •••••••••• ••••••••• •••••••• ••••••••• •••••••••• ••••••• Treatment of Solid metastatic tumor •••••••••••• ••••••••••• •••••• ••••••••• •• ••••• •••••••• •••••••••• ••••••••• •••••••• ••••••••• •••••••••• ••••••• Treatment of Tumors, solid •••••••••••• ••••••••••• •••••• ••••••••• ••••••• ••••••••••• ••••• •••••••• •••••••••• •• ••••• •••••••• •••••••••• ••••••••• •••••••••• ••••••••••• ••••••••• ••••••• ••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Entrectinib and its active metabolite suppress several pathways which contribute to cell survival and proliferation.2,4,5,6,7 This suppression shifts the balance in favor of apoptosis thereby preventing cancer cell growth and shrinking tumors.
- Mechanism of action
Entrectinib is a tyrosine kinase inhibitor which acts on several receptors. It functions as an ATP competitor to inhibit tropomyosin receptor tyrosine kinases (TRK) TRKA, TRKB, TRKC, as well as proto-oncogene tyrosine-protein kinase ROS1 and anaplastic lymphoma kinase (ALK).4,5,7 TRK receptors produce cell proliferation via downstream signalling through the mitogen activated protein kinase, phosphoinositide 3-kinase, and phospholipase C-γ.4 ALK produces similar signalling with the addition of downstream JAK/STAT activation.6 Inhibition of these pathways suppresses cancer cell proliferation and shifts the balance in favor of apoptosis resulting in shrinking of tumor volume.5
Target Actions Organism AHigh affinity nerve growth factor receptor inhibitorHumans ANT-3 growth factor receptor inhibitorHumans AProto-oncogene tyrosine-protein kinase ROS inhibitorHumans UBDNF/NT-3 growth factors receptor inhibitorHumans UTyrosine-protein kinase JAK2 inhibitorHumans UActivated CDC42 kinase 1 Not Available Humans - Absorption
Entrectinib has a Tmax of 4-5 h after administration of a single 600 mg dose.7 Food does not produce a significant effect on the extent of absorption.
- Volume of distribution
Entrectinib has an apparent volume of distribution of 551 L.7 The active metabolite, M5, has an apparent volume of distribution of 81.1 L. Entrectinib is known to cross the blood-brain barrier.4
- Protein binding
- Metabolism
CYP3A4 is responsible for 76% of entrectinib metabolism in humans including metabolism to the active metabolite, M5.7 M5 has similar pharmacological activity to entrectinib and exists at approximately 40% of the steady state concentration of the parent drug. In rats, six in vivo metabolites have been identified including N-dealkylated, N-oxide, hydroxylated, and glucuronide conjugated metabolites.3
Hover over products below to view reaction partners
- Route of elimination
After a single radio-labeled dose of entrectinib, 83% of radioactivity was present in the feces and 3% in the urine.7 Of the dose in the feces, 36% was present as entrectinib and 22% as M5.
- Half-life
Entrectinib has a half-life of elimination of 20 h.7 The active metabolite, M5, has a half-life of 40 h.
- Clearance
The apparent clearance of entrectinib is 19.6 L/h while the apparent clearance of the active metabolite M5 is 52.4 L/h.7
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Entrectinib can be increased when it is combined with Abametapir. Abatacept The metabolism of Entrectinib can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Entrectinib. Acalabrutinib The metabolism of Entrectinib can be decreased when combined with Acalabrutinib. Acebutolol The risk or severity of QTc prolongation can be increased when Acebutolol is combined with Entrectinib. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of entrectinib.
- Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of entrectinib.
- Take with or without food. Co-administration of food does not affect pharmacokinetics.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Rozlytrek Capsule 200 mg/1 Oral Genentech Inc. 2019-08-15 Not applicable US 
Rozlytrek Capsule 200 mg Oral Hoffmann La Roche 2020-03-04 Not applicable Canada 
Rozlytrek Capsule 200 mg/1 Oral Genentech, Inc. 2019-08-15 Not applicable US Rozlytrek Capsule 100 mg Oral Hoffmann La Roche 2020-03-10 Not applicable Canada Rozlytrek Capsule 100 mg/1 Oral Genentech, Inc. 2019-08-15 Not applicable US
Categories
- ATC Codes
- L01EX14 — Entrectinib
- Drug Categories
- Amides
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Benzene Derivatives
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Kinase Inhibitor
- Narrow Therapeutic Index Drugs
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Protein Kinase Inhibitors
- Pyrazoles
- QTc Prolonging Agents
- Tyrosine Kinase Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazinanes
- Sub Class
- Piperazines
- Direct Parent
- Phenylpiperazines
- Alternative Parents
- N-arylpiperazines / Aminobenzoic acids and derivatives / Anthranilamides / Indazoles / Aniline and substituted anilines / Benzoyl derivatives / Dialkylarylamines / Phenylalkylamines / Fluorobenzenes / Secondary alkylarylamines show 16 more
- Substituents
- Amine / Amino acid or derivatives / Aminobenzoic acid or derivatives / Aniline or substituted anilines / Anthranilamide / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Azole show 39 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- L5ORF0AN1I
- CAS number
- 1108743-60-7
- InChI Key
- HAYYBYPASCDWEQ-UHFFFAOYSA-N
- InChI
- InChI=1S/C31H34F2N6O2/c1-38-8-10-39(11-9-38)25-3-4-26(29(19-25)34-24-6-12-41-13-7-24)31(40)35-30-27-17-20(2-5-28(27)36-37-30)14-21-15-22(32)18-23(33)16-21/h2-5,15-19,24,34H,6-14H2,1H3,(H2,35,36,37,40)
- IUPAC Name
- N-{5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl}-4-(4-methylpiperazin-1-yl)-2-[(oxan-4-yl)amino]benzamide
- SMILES
- CN1CCN(CC1)C1=CC=C(C(=O)NC2=NNC3=CC=C(CC4=CC(F)=CC(F)=C4)C=C23)C(NC2CCOCC2)=C1
References
- Synthesis Reference
US Patent 20190135784A1
- General References
- Al-Salama ZT, Keam SJ: Entrectinib: First Global Approval. Drugs. 2019 Aug 1. pii: 10.1007/s40265-019-01177-y. doi: 10.1007/s40265-019-01177-y. [Article]
- Liu D, Offin M, Harnicar S, Li BT, Drilon A: Entrectinib: an orally available, selective tyrosine kinase inhibitor for the treatment of NTRK, ROS1, and ALK fusion-positive solid tumors. Ther Clin Risk Manag. 2018 Jul 20;14:1247-1252. doi: 10.2147/TCRM.S147381. eCollection 2018. [Article]
- Attwa MW, Kadi AA, Alrabiah H, Darwish HW: LC-MS/MS reveals the formation of iminium and quinone methide reactive intermediates in entrectinib metabolism: In vivo and in vitro metabolic investigation. J Pharm Biomed Anal. 2018 Oct 25;160:19-30. doi: 10.1016/j.jpba.2018.07.032. Epub 2018 Jul 22. [Article]
- Rolfo C, Ruiz R, Giovannetti E, Gil-Bazo I, Russo A, Passiglia F, Giallombardo M, Peeters M, Raez L: Entrectinib: a potent new TRK, ROS1, and ALK inhibitor. Expert Opin Investig Drugs. 2015;24(11):1493-500. doi: 10.1517/13543784.2015.1096344. Epub 2015 Oct 12. [Article]
- Ardini E, Menichincheri M, Banfi P, Bosotti R, De Ponti C, Pulci R, Ballinari D, Ciomei M, Texido G, Degrassi A, Avanzi N, Amboldi N, Saccardo MB, Casero D, Orsini P, Bandiera T, Mologni L, Anderson D, Wei G, Harris J, Vernier JM, Li G, Felder E, Donati D, Isacchi A, Pesenti E, Magnaghi P, Galvani A: Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications. Mol Cancer Ther. 2016 Apr;15(4):628-39. doi: 10.1158/1535-7163.MCT-15-0758. Epub 2016 Mar 3. [Article]
- Pacenta HL, Macy ME: Entrectinib and other ALK/TRK inhibitors for the treatment of neuroblastoma. Drug Des Devel Ther. 2018 Oct 23;12:3549-3561. doi: 10.2147/DDDT.S147384. eCollection 2018. [Article]
- FDA Approved Drug Productsl: Rozlytrek (entrectinib) capsules for oral use [Link]
- Cayman Chemical: Entrectinib MSDS [Link]
- FDA Announcement: Entrectinib Approval [Link]
- BioSpace: FoundationOne®Liquid CDx Receives FDA Approval as a Companion Diagnostic for Rozlytrek® (entrectinib) [Link]
- External Links
- Human Metabolome Database
- HMDB0304880
- PubChem Compound
- 25141092
- PubChem Substance
- 347828307
- ChemSpider
- 24808589
- BindingDB
- 158154
- 2197862
- ChEMBL
- CHEMBL1983268
- ZINC
- ZINC000043204146
- PDBe Ligand
- YMX
- Wikipedia
- Entrectinib
- PDB Entries
- 5fto / 5kvt
- FDA label
- Download (830 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Recruiting Treatment Non-Small Cell Lung Cancer (NSCLC) 1 3 Recruiting Treatment Non-Small Cell Lung Carcinoma 1 2 Active Not Recruiting Treatment Adult Solid Tumor / Anaplastic Large Cell Lymphoma / Breast Cancer / Cholangiocarcinoma / Colorectal Cancer / Head and Neck Neoplasms / Melanoma / Neuroendocrine Tumors / Non-Small Cell Lung Cancer (NSCLC) / Ovarian Cancer / Pancreatic Cancer / Primary Brain Neoplasm / Renal Cell Carcinoma (RCC) / Salivary Gland Cancers / Sarcomas / Thyroid Cancer, Papillary 1 2 Active Not Recruiting Treatment Advanced Unresectable or Metastatic Solid Malignancy 1 2 Active Not Recruiting Treatment Breast Cancer / Gastrointestinal Tract Cancer / Non-Small Cell Lung Cancer (NSCLC) / Other Cancers 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 100 mg Capsule Oral 100 mg/1 Capsule Oral 200 mg Capsule Oral 200 mg/1 Pellet Oral 50 mg/201 Capsule Oral 100.000 mg Capsule Oral 200.00 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9616059 No 2017-04-11 2028-07-08 US US10231965 No 2019-03-19 2035-02-17 US US9649306 No 2017-05-16 2033-05-22 US US8673893 No 2014-03-18 2028-07-08 US US9255087 No 2016-02-09 2028-07-08 US US9029356 No 2015-05-12 2028-07-08 US US9085565 No 2015-07-21 2033-05-22 US US8299057 No 2012-10-30 2029-03-01 US US10398693 No 2019-09-03 2038-07-18 US US9085558 No 2015-07-21 2028-07-08 US US10561651 No 2020-02-18 2035-02-19 US US10738037 No 2020-08-11 2037-05-18 US US11091469 No 2021-08-17 2037-05-18 US US11253515 No 2018-07-18 2038-07-18 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0089 mg/mL ALOGPS logP 5.03 ALOGPS logP 5.4 Chemaxon logS -4.8 ALOGPS pKa (Strongest Acidic) 12.39 Chemaxon pKa (Strongest Basic) 7.78 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 85.52 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 161.24 m3·mol-1 Chemaxon Polarizability 60.41 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 229.7359 predictedDeepCCS 1.0 (2019) [M+H]+ 232.1007 predictedDeepCCS 1.0 (2019) [M+Na]+ 238.01399 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- 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
- Liu D, Offin M, Harnicar S, Li BT, Drilon A: Entrectinib: an orally available, selective tyrosine kinase inhibitor for the treatment of NTRK, ROS1, and ALK fusion-positive solid tumors. Ther Clin Risk Manag. 2018 Jul 20;14:1247-1252. doi: 10.2147/TCRM.S147381. eCollection 2018. [Article]
- Rolfo C, Ruiz R, Giovannetti E, Gil-Bazo I, Russo A, Passiglia F, Giallombardo M, Peeters M, Raez L: Entrectinib: a potent new TRK, ROS1, and ALK inhibitor. Expert Opin Investig Drugs. 2015;24(11):1493-500. doi: 10.1517/13543784.2015.1096344. Epub 2015 Oct 12. [Article]
- Ardini E, Menichincheri M, Banfi P, Bosotti R, De Ponti C, Pulci R, Ballinari D, Ciomei M, Texido G, Degrassi A, Avanzi N, Amboldi N, Saccardo MB, Casero D, Orsini P, Bandiera T, Mologni L, Anderson D, Wei G, Harris J, Vernier JM, Li G, Felder E, Donati D, Isacchi A, Pesenti E, Magnaghi P, Galvani A: Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications. Mol Cancer Ther. 2016 Apr;15(4):628-39. doi: 10.1158/1535-7163.MCT-15-0758. Epub 2016 Mar 3. [Article]
- Pacenta HL, Macy ME: Entrectinib and other ALK/TRK inhibitors for the treatment of neuroblastoma. Drug Des Devel Ther. 2018 Oct 23;12:3549-3561. doi: 10.2147/DDDT.S147384. eCollection 2018. [Article]
- FDA Approved Drug Productsl: Rozlytrek (entrectinib) capsules for oral use [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
- Liu D, Offin M, Harnicar S, Li BT, Drilon A: Entrectinib: an orally available, selective tyrosine kinase inhibitor for the treatment of NTRK, ROS1, and ALK fusion-positive solid tumors. Ther Clin Risk Manag. 2018 Jul 20;14:1247-1252. doi: 10.2147/TCRM.S147381. eCollection 2018. [Article]
- Rolfo C, Ruiz R, Giovannetti E, Gil-Bazo I, Russo A, Passiglia F, Giallombardo M, Peeters M, Raez L: Entrectinib: a potent new TRK, ROS1, and ALK inhibitor. Expert Opin Investig Drugs. 2015;24(11):1493-500. doi: 10.1517/13543784.2015.1096344. Epub 2015 Oct 12. [Article]
- Ardini E, Menichincheri M, Banfi P, Bosotti R, De Ponti C, Pulci R, Ballinari D, Ciomei M, Texido G, Degrassi A, Avanzi N, Amboldi N, Saccardo MB, Casero D, Orsini P, Bandiera T, Mologni L, Anderson D, Wei G, Harris J, Vernier JM, Li G, Felder E, Donati D, Isacchi A, Pesenti E, Magnaghi P, Galvani A: Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications. Mol Cancer Ther. 2016 Apr;15(4):628-39. doi: 10.1158/1535-7163.MCT-15-0758. Epub 2016 Mar 3. [Article]
- Pacenta HL, Macy ME: Entrectinib and other ALK/TRK inhibitors for the treatment of neuroblastoma. Drug Des Devel Ther. 2018 Oct 23;12:3549-3561. doi: 10.2147/DDDT.S147384. eCollection 2018. [Article]
- FDA Approved Drug Productsl: Rozlytrek (entrectinib) capsules for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Orphan receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. May activate several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. Mediates the phosphorylation of PTPN11, an activator of this pathway. May also phosphorylate and activate the transcription factor STAT3 to control anchorage-independent cell growth. Mediates the phosphorylation and the activation of VAV3, a guanine nucleotide exchange factor regulating cell morphology. May activate other downstream signaling proteins including AKT1, MAPK1, MAPK3, IRS1 and PLCG2.
- Specific Function
- Atp binding
- Gene Name
- ROS1
- Uniprot ID
- P08922
- Uniprot Name
- Proto-oncogene tyrosine-protein kinase ROS
- Molecular Weight
- 263912.88 Da
References
- Liu D, Offin M, Harnicar S, Li BT, Drilon A: Entrectinib: an orally available, selective tyrosine kinase inhibitor for the treatment of NTRK, ROS1, and ALK fusion-positive solid tumors. Ther Clin Risk Manag. 2018 Jul 20;14:1247-1252. doi: 10.2147/TCRM.S147381. eCollection 2018. [Article]
- Rolfo C, Ruiz R, Giovannetti E, Gil-Bazo I, Russo A, Passiglia F, Giallombardo M, Peeters M, Raez L: Entrectinib: a potent new TRK, ROS1, and ALK inhibitor. Expert Opin Investig Drugs. 2015;24(11):1493-500. doi: 10.1517/13543784.2015.1096344. Epub 2015 Oct 12. [Article]
- Ardini E, Menichincheri M, Banfi P, Bosotti R, De Ponti C, Pulci R, Ballinari D, Ciomei M, Texido G, Degrassi A, Avanzi N, Amboldi N, Saccardo MB, Casero D, Orsini P, Bandiera T, Mologni L, Anderson D, Wei G, Harris J, Vernier JM, Li G, Felder E, Donati D, Isacchi A, Pesenti E, Magnaghi P, Galvani A: Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications. Mol Cancer Ther. 2016 Apr;15(4):628-39. doi: 10.1158/1535-7163.MCT-15-0758. Epub 2016 Mar 3. [Article]
- Pacenta HL, Macy ME: Entrectinib and other ALK/TRK inhibitors for the treatment of neuroblastoma. Drug Des Devel Ther. 2018 Oct 23;12:3549-3561. doi: 10.2147/DDDT.S147384. eCollection 2018. [Article]
- FDA Approved Drug Productsl: Rozlytrek (entrectinib) capsules for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Liu D, Offin M, Harnicar S, Li BT, Drilon A: Entrectinib: an orally available, selective tyrosine kinase inhibitor for the treatment of NTRK, ROS1, and ALK fusion-positive solid tumors. Ther Clin Risk Manag. 2018 Jul 20;14:1247-1252. doi: 10.2147/TCRM.S147381. eCollection 2018. [Article]
- Rolfo C, Ruiz R, Giovannetti E, Gil-Bazo I, Russo A, Passiglia F, Giallombardo M, Peeters M, Raez L: Entrectinib: a potent new TRK, ROS1, and ALK inhibitor. Expert Opin Investig Drugs. 2015;24(11):1493-500. doi: 10.1517/13543784.2015.1096344. Epub 2015 Oct 12. [Article]
- Ardini E, Menichincheri M, Banfi P, Bosotti R, De Ponti C, Pulci R, Ballinari D, Ciomei M, Texido G, Degrassi A, Avanzi N, Amboldi N, Saccardo MB, Casero D, Orsini P, Bandiera T, Mologni L, Anderson D, Wei G, Harris J, Vernier JM, Li G, Felder E, Donati D, Isacchi A, Pesenti E, Magnaghi P, Galvani A: Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications. Mol Cancer Ther. 2016 Apr;15(4):628-39. doi: 10.1158/1535-7163.MCT-15-0758. Epub 2016 Mar 3. [Article]
- Pacenta HL, Macy ME: Entrectinib and other ALK/TRK inhibitors for the treatment of neuroblastoma. Drug Des Devel Ther. 2018 Oct 23;12:3549-3561. doi: 10.2147/DDDT.S147384. eCollection 2018. [Article]
- FDA Approved Drug Productsl: Rozlytrek (entrectinib) capsules for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sh2 domain binding
- Specific Function
- Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptiv...
- Gene Name
- JAK2
- Uniprot ID
- O60674
- Uniprot Name
- Tyrosine-protein kinase JAK2
- Molecular Weight
- 130672.475 Da
References
- FDA Approved Drug Productsl: Rozlytrek (entrectinib) capsules for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Ww domain binding
- Specific Function
- Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals ...
- Gene Name
- TNK2
- Uniprot ID
- Q07912
- Uniprot Name
- Activated CDC42 kinase 1
- Molecular Weight
- 114567.605 Da
References
- FDA Approved Drug Productsl: Rozlytrek (entrectinib) capsules for oral use [Link]
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
References
- Al-Salama ZT, Keam SJ: Entrectinib: First Global Approval. Drugs. 2019 Aug 1. pii: 10.1007/s40265-019-01177-y. doi: 10.1007/s40265-019-01177-y. [Article]
- Liu D, Offin M, Harnicar S, Li BT, Drilon A: Entrectinib: an orally available, selective tyrosine kinase inhibitor for the treatment of NTRK, ROS1, and ALK fusion-positive solid tumors. Ther Clin Risk Manag. 2018 Jul 20;14:1247-1252. doi: 10.2147/TCRM.S147381. eCollection 2018. [Article]
- FDA Approved Drug Productsl: Rozlytrek (entrectinib) capsules for oral use [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- The active metabolite M5 is a substrate of P-gp. The parent drug does is an inhibitor of P-gp, but not a 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
Drug created at October 20, 2016 21:08 / Updated at November 01, 2023 04:04