entrectinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| tyrosine kinase inhibitors | 5345 | 1108743-60-7 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
Entrectinib is an inhibitor of the tropomyosin receptor tyrosine kinases (TRK) TRKA, TRKB, and TRKC (encoded by the neurotrophic tyrosine receptor kinase [NTRK] genes NTRK1, NTRK2, and NTRK3, respectively), proto-oncogene tyrosine-protein kinase ROS1 (ROS1), and anaplastic lymphoma kinase (ALK).
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
| Dose | Unit | Route |
|---|---|---|
| 0.60 | g | O |
ADMET properties:
| Property | Value | Reference |
|---|---|---|
| S (Water solubility) | 0.00 mg/mL | Bocci G, Oprea TI, Benet LZ |
| BDDCS (Biopharmaceutical Drug Disposition Classification System) | 2 | Bocci G, Oprea TI, Benet LZ |
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| Aug. 15, 2019 | FDA | GENENTECH INC | |
| June 18, 2019 | PMDA | Chugai Pharmaceutical |
FDA Adverse Event Reporting System (Female)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Ataxia | 68.99 | 47.96 | 17 | 446 | 15178 | 63473381 |
| Renal impairment | 56.82 | 47.96 | 22 | 441 | 88333 | 63400226 |
FDA Adverse Event Reporting System (Male)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Taste disorder | 43.68 | 40.97 | 11 | 370 | 7144 | 34949406 |
FDA Adverse Event Reporting System (Geriatric)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Taste disorder | 91.59 | 44.08 | 23 | 789 | 15800 | 79727776 |
| Renal impairment | 68.96 | 44.08 | 33 | 779 | 157750 | 79585826 |
| Ataxia | 63.38 | 44.08 | 19 | 793 | 25020 | 79718556 |
| Disease progression | 58.34 | 44.08 | 31 | 781 | 184331 | 79559245 |
| Blood creatinine increased | 54.53 | 44.08 | 28 | 784 | 155029 | 79588547 |
FDA Adverse Event Reporting System (Pediatric)
None
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | L01EX14 | ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS Other protein kinase inhibitors |
| MeSH PA | D004791 | Enzyme Inhibitors |
| MeSH PA | D047428 | Protein Kinase Inhibitors |
| CHEBI has role | CHEBI:33282 | bactericides |
| CHEBI has role | CHEBI:35610 | antineoplastic agents |
| CHEBI has role | CHEBI:62434 | ALK inhibitor |
| CHEBI has role | CHEBI:68495 | Type I cell-death inducers |
Drug Use | Suggest Off label Use Form| |View source of the data|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Reactive oxygen species 1 positive non-small cell lung cancer | indication | 72242500 | |
| Solid neoplasm with neurotrophic receptor tyrosine kinase gene fusion | indication | 786710002 |
🐶 Veterinary Drug Use
None
🐶 Veterinary products
None
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (acidic/basic) |
|---|---|---|
| pKa1 | 11.61 | acidic |
| pKa2 | 12.21 | acidic |
| pKa3 | 8.43 | Basic |
| pKa4 | 1.79 | Basic |
| pKa5 | 1.11 | Basic |
Orange Book patent data (new drug applications)
| Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Patent number | Patent expiration date | Patent use |
|---|---|---|---|---|---|---|---|---|---|---|
| 100MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 8673893 | July 8, 2028 | TREATMENT OF ROS1-POSITIVE NON-SMALL CELL LUNG CANCER |
| 100MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 8673893 | July 8, 2028 | TREATMENT OF SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION |
| 100MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 9255087 | July 8, 2028 | TREATMENT OF ROS1-POSITIVE NON-SMALL CELL LUNG CANCER |
| 100MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 9255087 | July 8, 2028 | TREATMENT OF SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION |
| 100MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 9616059 | July 8, 2028 | TREATMENT OF SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION |
| 200MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 8673893 | July 8, 2028 | TREATMENT OF ROS1-POSITIVE NON-SMALL CELL LUNG CANCER |
| 200MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 8673893 | July 8, 2028 | TREATMENT OF SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION |
| 200MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 9255087 | July 8, 2028 | TREATMENT OF ROS1-POSITIVE NON-SMALL CELL LUNG CANCER |
| 200MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 9255087 | July 8, 2028 | TREATMENT OF SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION |
| 200MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 9616059 | July 8, 2028 | TREATMENT OF SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION |
| 100MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 9649306 | May 22, 2033 | TREATMENT OF ROS1-POSITIVE NON-SMALL CELL LUNG CANCER |
| 100MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 9649306 | May 22, 2033 | TREATMENT OF SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION |
| 200MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 9649306 | May 22, 2033 | TREATMENT OF ROS1-POSITIVE NON-SMALL CELL LUNG CANCER |
| 200MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 9649306 | May 22, 2033 | TREATMENT OF SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION |
| 100MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 10231965 | Feb. 17, 2035 | TREATMENT OF ROS1-POSITIVE NON-SMALL CELL LUNG CANCER |
| 100MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 10231965 | Feb. 17, 2035 | TREATMENT OF SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION |
| 200MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 10231965 | Feb. 17, 2035 | TREATMENT OF ROS1-POSITIVE NON-SMALL CELL LUNG CANCER |
| 200MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 10231965 | Feb. 17, 2035 | TREATMENT OF SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION |
| 100MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 10561651 | Feb. 19, 2035 | TREATMENT OF NEUROBLASTOMAS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION |
| 200MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 10561651 | Feb. 19, 2035 | TREATMENT OF NEUROBLASTOMAS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION |
| 100MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 10738037 | May 18, 2037 | TREATMENT OF COLORECTAL CANCER THAT HAS A NEUROTROPHIC TYROSINE RECEPTOR KINASE(NTRK) GENE FUSION |
| 100MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 11091469 | May 18, 2037 | TREATMENT OF ROS1-POSITIVE NON-SMALL CELL LUNG CANCER |
| 100MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 11091469 | May 18, 2037 | TREATMENT OF SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION |
| 200MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 10738037 | May 18, 2037 | TREATMENT OF COLORECTAL CANCER THAT HAS A NEUROTROPHIC TYROSINE RECEPTOR KINASE(NTRK) GENE FUSION |
| 200MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 11091469 | May 18, 2037 | TREATMENT OF ROS1-POSITIVE NON-SMALL CELL LUNG CANCER |
| 200MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | 11091469 | May 18, 2037 | TREATMENT OF SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION |
Orange Book exclusivity data (new drug applications)
| Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Exclusivity date | Description |
|---|---|---|---|---|---|---|---|---|---|
| 100MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | Aug. 15, 2024 | NEW CHEMICAL ENTITY |
| 200MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | Aug. 15, 2024 | NEW CHEMICAL ENTITY |
| 100MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | Aug. 15, 2026 | INDICATED FOR THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER WITH SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION WITHOUT A KNOWN ACQUIRED RESISTENACE MUTATION, ARE METASTATIC OR WHERE SURGICAL RESECTION IS LIKELY TO RESULT IN SEVERE MORBIDITY, AND HAVE EITHER PROGRESSED FOLLOWING TREATMENT OR HAVE NO SATISFACTORY ALTERNATIVE THERAPY |
| 100MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | Aug. 15, 2026 | INDICATED FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS ARE ROS1-POSITIVE |
| 200MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | Aug. 15, 2026 | INDICATED FOR THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER WITH SOLID TUMORS THAT HAVE A NEUROTROPHIC TYROSINE RECEPTOR KINASE (NTRK) GENE FUSION WITHOUT A KNOWN ACQUIRED RESISTENACE MUTATION, ARE METASTATIC OR WHERE SURGICAL RESECTION IS LIKELY TO RESULT IN SEVERE MORBIDITY, AND HAVE EITHER PROGRESSED FOLLOWING TREATMENT OR HAVE NO SATISFACTORY ALTERNATIVE THERAPY |
| 200MG | ROZLYTREK | GENENTECH INC | N212725 | Aug. 15, 2019 | RX | CAPSULE | ORAL | Aug. 15, 2026 | INDICATED FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS ARE ROS1-POSITIVE |
Bioactivity Summary:
| Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA source |
|---|---|---|---|---|---|---|---|---|---|
| High affinity nerve growth factor receptor | Kinase | INHIBITOR | IC50 | 9 | SCIENTIFIC LITERATURE | DRUG LABEL | |||
| ALK tyrosine kinase receptor | Kinase | INHIBITOR | IC50 | 7.92 | SCIENTIFIC LITERATURE | DRUG LABEL | |||
| BDNF/NT-3 growth factors receptor | Kinase | INHIBITOR | IC50 | 8.52 | SCIENTIFIC LITERATURE | DRUG LABEL | |||
| NT-3 growth factor receptor | Kinase | INHIBITOR | IC50 | 8.30 | SCIENTIFIC LITERATURE | DRUG LABEL | |||
| Proto-oncogene tyrosine-protein kinase ROS | Kinase | INHIBITOR | IC50 | 8.15 | SCIENTIFIC LITERATURE | DRUG LABEL | |||
| Focal adhesion kinase 1 | Kinase | IC50 | 6.85 | CHEMBL | |||||
| Tyrosine-protein kinase JAK1 | Kinase | IC50 | 6.95 | CHEMBL | |||||
| Aurora kinase A | Kinase | IC50 | 6.67 | CHEMBL | |||||
| Protein-tyrosine kinase 6 | Kinase | IC50 | 6.71 | CHEMBL | |||||
| Tyrosine-protein kinase JAK3 | Kinase | IC50 | 6.46 | CHEMBL | |||||
| Aurora kinase B | Kinase | IC50 | 6.47 | CHEMBL | |||||
| Serine/threonine-protein kinase LMTK3 | Kinase | IC50 | 5.33 | CHEMBL | |||||
| Tyrosine-protein kinase JAK2 | Kinase | INHIBITOR | IC50 | 7.40 | SCIENTIFIC LITERATURE | ||||
| Activated CDC42 kinase 1 | Kinase | INHIBITOR | IC50 | 7.15 | SCIENTIFIC LITERATURE | ||||
| Non-receptor tyrosine-protein kinase TNK1 | Kinase | Kd | 5.83 | CHEMBL | |||||
| Receptor-type tyrosine-protein kinase FLT3 | Kinase | IC50 | 6.79 | CHEMBL | |||||
| Proto-oncogene tyrosine-protein kinase receptor Ret | Kinase | IC50 | 6.41 | CHEMBL | |||||
| Insulin-like growth factor 1 receptor | Kinase | IC50 | 6.91 | CHEMBL | |||||
| Insulin receptor | Kinase | IC50 | 6.68 | CHEMBL |
External reference:
| ID | Source |
|---|---|
| L5ORF0AN1I | UNII |
| C4086264 | UMLSCUI |
| CHEBI:195558 | CHEBI |
| YMX | PDB_CHEM_ID |
| CHEMBL1983268 | ChEMBL_ID |
| 25141092 | PUBCHEM_CID |
| DB11986 | DRUGBANK_ID |
| D10926 | KEGG_DRUG |
| 10132 | INN_ID |
| 8290 | IUPHAR_LIGAND_ID |
| 018089 | NDDF |
| 789356007 | SNOMEDCT_US |
| 789364001 | SNOMEDCT_US |
| 4038664 | VANDF |
| 2197862 | RXNORM |
| 322129 | MMSL |
| 37312 | MMSL |
| d09348 | MMSL |
| C000607349 | MESH_SUPPLEMENTAL_RECORD_UI |
Pharmaceutical products:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| Rozlytrek | HUMAN PRESCRIPTION DRUG LABEL | 1 | 50242-091 | CAPSULE | 100 mg | ORAL | NDA | 30 sections |
| Rozlytrek | HUMAN PRESCRIPTION DRUG LABEL | 1 | 50242-091 | CAPSULE | 100 mg | ORAL | NDA | 30 sections |
| Rozlytrek | HUMAN PRESCRIPTION DRUG LABEL | 1 | 50242-091 | CAPSULE | 100 mg | ORAL | NDA | 30 sections |
| Rozlytrek | HUMAN PRESCRIPTION DRUG LABEL | 1 | 50242-094 | CAPSULE | 200 mg | ORAL | NDA | 30 sections |
| Rozlytrek | HUMAN PRESCRIPTION DRUG LABEL | 1 | 50242-094 | CAPSULE | 200 mg | ORAL | NDA | 30 sections |
| Rozlytrek | HUMAN PRESCRIPTION DRUG LABEL | 1 | 50242-094 | CAPSULE | 200 mg | ORAL | NDA | 30 sections |