Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C21H22F2N6O2.ClH |
Molecular Weight | 464.896 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.[H][C@@]1(CCCN1C2=NC3=C(NC(=O)N4CC[C@H](O)C4)C=NN3C=C2)C5=C(F)C=CC(F)=C5
InChI
InChIKey=UIHKJNYGFOAQDS-QLOBERJESA-N
InChI=1S/C21H22F2N6O2.ClH/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);1H/t14-,18+;/m0./s1
Molecular Formula | C21H22F2N6O2 |
Molecular Weight | 428.4352 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Molecular Formula | ClH |
Molecular Weight | 36.461 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Larotrectinib (previously known as ARRY-470 and LOXO-101) is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Larotrectinib is in phase II clinical trials for the treatment patients with solid tumors, non-Hodgkin lymphoma and for the pediatric patients with advanced solid or primary CNS tumors.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21138586
Curator's Comment: Known to be CNS non-penetrant in mouse. Human data not available
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3559684 |
|||
Target ID: CHEMBL2815 |
20.0 nM [IC50] | ||
Target ID: CHEMBL4898 |
20.0 nM [IC50] | ||
Target ID: CHEMBL5608 |
20.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | VITRAKVI Approved UseVitrakvi is specifically indicated for the treatment of adult and pediatric patients with solid tumors that: • have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, • are metastatic or where surgical resection is likely to result in severe morbidity, and • have no satisfactory alternative treatments or that have progressed following treatment. Launch Date2018 |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
788 ng/mL |
100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LAROTRECTINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4351 ng × h/mL |
100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LAROTRECTINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.9 h |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
LAROTRECTINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Disc. AE: Brain edema, Intestinal perforation... Other AEs: Fatigue, Nausea... AEs leading to discontinuation/dose reduction: Brain edema (1 - 2) Other AEs:Intestinal perforation (1 - 2) Pericardial effusion (1 - 2) Pleural effusion (1 - 2) Small intestinal obstruction (1 - 2) Dehydration (1 - 2) Fatigue (1 - 2) ALT increased (1 - 2) AST increased (1 - 2) Enterocutaneous fistula (1 - 2) Amylase increased (1 - 2) Lipase increased (1 - 2) Muscular weakness (1 - 2) Abdominal pain (1 - 2) Asthenia (1 - 2) Decreased appetite (1 - 2) Dyspnea (1 - 2) Hyponatremia (1 - 2) Jaundice (1 - 2) Syncope (1 - 2) Vomiting (1 - 2) Nausea (1 - 2) Acute myeloid leukemia (1 - 2) Fatigue (>20) Sources: Page: 6.1Nausea (>20) Dizziness (>20) Vomiting (>20) Anemia (>20) AST increased (>20) Cough (>20) ALT increased (>20) Constipation (>20) Diarrhea (>20) ALT increased (6%) AST increased (6%) Dizziness (3%) |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Other AEs: Fatigue, Pyrexia... Other AEs: Fatigue (all grades, 37%) Sources: Page: Table 2Pyrexia (all grades, 18%) Edema peripheral (all grades, 15%) Nausea (all grades, 29%) Vomiting (all grades, 26%) Constipation (all grades, 23%) Diarrhea (all grades, 22%) Abdominal pain (all grades, 13%) Dizziness (all grades, 28%) Headache (all grades, 14%) Cough (all grades, 26%) Dyspnea (all grades, 18%) Nasal congestion (all grades, 10%) Fatigue (grade 3-4, 3%) Pyrexia (grade 3-4, 1%) Nausea (grade 3-4, 1%) Vomiting (grade 3-4, 1%) Constipation (grade 3-4, 1%) Diarrhea (grade 3-4, 2%) Abdominal pain (grade 3-4, 2%) Dizziness (grade 3-4, 1%) Dyspnea (grade 3-4, 2%) Weight increased (all grades, 15%) Arthralgia (all grades, 14%) Myalgia (all grades, 14%) Muscular weakness (all grades, 13%) Back pain (all grades, 12%) Pain in extremity (all grades, 12%) Decreased appetite (all grades, 13%) Decreased appetite (all grades, 11%) Weight increased (grade 3-4, 4%) Arthralgia (grade 3-4, 1%) Myalgia (grade 3-4, 1%) Back pain (grade 3-4, 1%) Pain in extremity (grade 3-4, 1%) Decreased appetite (grade 3-4, 2%) Decreased appetite (grade 3-4, 2%) |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 3 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 3 |
Other AEs: ALT increased, AST increased... Other AEs: ALT increased (all grades, 45%) Sources: Page: Table 3AST increased (all grades, 45%) Hypoalbuminemia (all grades, 35%) Alkaline phosphatase increased (all grades, 30%) Anemia (all grades, 42%) Neutropenia (all grades, 23%) ALT increased (grade 3-4, 3%) AST increased (grade 3-4, 3%) Hypoalbuminemia (grade 3-4, 2%) Alkaline phosphatase increased (grade 3-4, 3%) Anemia (grade 3-4, 10%) Neutropenia (grade 3-4, 7%) |
150 mg 2 times / day steady, oral Higher than recommended Dose: 150 mg, 2 times / day Route: oral Route: steady Dose: 150 mg, 2 times / day Sources: |
unhealthy, adult n = 7 Health Status: unhealthy Condition: solid tumours Age Group: adult Sex: unknown Population Size: 7 Sources: |
DLT: Alanine aminotransferase increased, Aspartate aminotransferase increased... Dose limiting toxicities: Alanine aminotransferase increased (1 patient) Sources: Aspartate aminotransferase increased (1 patient) |
200 mg 2 times / day steady, oral Highest studied dose Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: |
unhealthy, adult n = 6 Health Status: unhealthy Condition: solid tumours Age Group: adult Sex: unknown Population Size: 6 Sources: |
DLT: Dizziness... |
200 mg 2 times / day steady, oral Highest studied dose Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: Page: 91 |
unhealthy, adult n = 6 Health Status: unhealthy Condition: solid tumor Age Group: adult Sex: unknown Population Size: 6 Sources: Page: 91 |
|
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 6 Health Status: unhealthy Condition: solid tumours Age Group: adult Sex: unknown Population Size: 6 Sources: |
DLT: Dizziness... |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
ALT increased | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
AST increased | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Abdominal pain | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Acute myeloid leukemia | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Amylase increased | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Asthenia | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Brain edema | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Decreased appetite | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Dehydration | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Dyspnea | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Enterocutaneous fistula | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Fatigue | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Hyponatremia | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Intestinal perforation | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Jaundice | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Lipase increased | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Muscular weakness | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Nausea | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Pericardial effusion | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Pleural effusion | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Small intestinal obstruction | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Syncope | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Vomiting | 1 - 2 Disc. AE |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Dizziness | 3% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
ALT increased | 6% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
AST increased | 6% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
ALT increased | >20 | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
AST increased | >20 | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Anemia | >20 | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Constipation | >20 | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Cough | >20 | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Diarrhea | >20 | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Dizziness | >20 | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Fatigue | >20 | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Nausea | >20 | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Vomiting | >20 | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: 6.1 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: 6.1 |
Nasal congestion | all grades, 10% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Decreased appetite | all grades, 11% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Back pain | all grades, 12% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Pain in extremity | all grades, 12% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Abdominal pain | all grades, 13% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Decreased appetite | all grades, 13% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Muscular weakness | all grades, 13% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Arthralgia | all grades, 14% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Headache | all grades, 14% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Myalgia | all grades, 14% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Edema peripheral | all grades, 15% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Weight increased | all grades, 15% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Dyspnea | all grades, 18% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Pyrexia | all grades, 18% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Diarrhea | all grades, 22% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Constipation | all grades, 23% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Cough | all grades, 26% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Vomiting | all grades, 26% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Dizziness | all grades, 28% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Nausea | all grades, 29% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Fatigue | all grades, 37% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Arthralgia | grade 3-4, 1% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Back pain | grade 3-4, 1% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Constipation | grade 3-4, 1% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Dizziness | grade 3-4, 1% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Myalgia | grade 3-4, 1% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Nausea | grade 3-4, 1% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Pain in extremity | grade 3-4, 1% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Pyrexia | grade 3-4, 1% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Vomiting | grade 3-4, 1% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Abdominal pain | grade 3-4, 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Decreased appetite | grade 3-4, 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Decreased appetite | grade 3-4, 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Diarrhea | grade 3-4, 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Dyspnea | grade 3-4, 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Fatigue | grade 3-4, 3% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Weight increased | grade 3-4, 4% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 2 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 2 |
Neutropenia | all grades, 23% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 3 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 3 |
Alkaline phosphatase increased | all grades, 30% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 3 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 3 |
Hypoalbuminemia | all grades, 35% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 3 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 3 |
Anemia | all grades, 42% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 3 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 3 |
ALT increased | all grades, 45% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 3 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 3 |
AST increased | all grades, 45% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 3 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 3 |
Anemia | grade 3-4, 10% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 3 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 3 |
Hypoalbuminemia | grade 3-4, 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 3 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 3 |
ALT increased | grade 3-4, 3% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 3 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 3 |
AST increased | grade 3-4, 3% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 3 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 3 |
Alkaline phosphatase increased | grade 3-4, 3% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 3 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 3 |
Neutropenia | grade 3-4, 7% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: Page: Table 3 |
unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: Page: Table 3 |
Alanine aminotransferase increased | 1 patient DLT |
150 mg 2 times / day steady, oral Higher than recommended Dose: 150 mg, 2 times / day Route: oral Route: steady Dose: 150 mg, 2 times / day Sources: |
unhealthy, adult n = 7 Health Status: unhealthy Condition: solid tumours Age Group: adult Sex: unknown Population Size: 7 Sources: |
Aspartate aminotransferase increased | 1 patient DLT |
150 mg 2 times / day steady, oral Higher than recommended Dose: 150 mg, 2 times / day Route: oral Route: steady Dose: 150 mg, 2 times / day Sources: |
unhealthy, adult n = 7 Health Status: unhealthy Condition: solid tumours Age Group: adult Sex: unknown Population Size: 7 Sources: |
Dizziness | 1 patient DLT |
200 mg 2 times / day steady, oral Highest studied dose Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: |
unhealthy, adult n = 6 Health Status: unhealthy Condition: solid tumours Age Group: adult Sex: unknown Population Size: 6 Sources: |
Dizziness | 1 patient DLT |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 6 Health Status: unhealthy Condition: solid tumours Age Group: adult Sex: unknown Population Size: 6 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes | yes (co-administration study) Comment: larotrectinib increased midazolam both AUC and Cmax by 1.7-fold Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 94.0 |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes [Km >300 uM] | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 93, 94, 106 |
yes [Km >300 uM] | yes (co-administration study) Comment: rifampin increased larotrectinib AUC by 1.7-fold and Cmax by 1.8-fold Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 93, 94, 106 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf#page=95 Page: 95, 104, 105 |
yes | yes (co-administration study) Comment: coadministration with midazolam increased midazolam AUC and Cmax by 1.7-fold; itraconazole increased larotrectinib AUC by 4.3-fold and Cmax by 2.8-fold; rifampin decreased larotrectinib AUC by 81% and Cmax by 71% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf#page=95 Page: 95, 104, 105 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 44, 51, 182 |
PubMed
Title | Date | PubMed |
---|---|---|
Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. | 2013 Nov |
|
An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101. | 2015 Oct |
|
Targeting NTRK fusion in non-small cell lung cancer: rationale and clinical evidence. | 2017 Jun |
|
Rapid Response to Larotrectinib (LOXO-101) in an Adult Chemotherapy-Naive Patients With Advanced Triple-Negative Secretory Breast Cancer Expressing ETV6-NTRK3 Fusion. | 2018 Jun |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT02576431
Oral capsule of LOXO-101 (ARRY-470 (FREE BASE)) - 100mg BID
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24162815
ARRY-470 is a selective kinase inhibitor with nanomolar activity against TRKA/B/C but no other significant kinase inhibition below 1000nM. Treatment of cells expressing MPRIP- or CD74-NTRK1 with ARRY-470, CEP-701 and, to a lesser extent, crizotinib, inhibited autophosphorylation of RIP-TRKA and CD74-TRKA. It induces cell-cycle arrest in G1 and apoptosis of KM12 cells.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 19:32:10 GMT 2023
by
admin
on
Sat Dec 16 19:32:10 GMT 2023
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Record UNII |
E4BVS4JUA7
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Record Status |
Validated (UNII)
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Record Version |
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1919868-83-9
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121333501
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PARENT -> SALT/SOLVATE |
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