Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C21H19FN6O2.C2H4O2 |
Molecular Weight | 466.4649 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(O)=O.C[C@H]1OC2=CC(=CN=C2N)C3=C(C#N)N(C)N=C3CN(C)C(=O)C4=CC=C(F)C=C14
InChI
InChIKey=BLNAIBLTPYGILH-RFVHGSKJSA-N
InChI=1S/C21H19FN6O2.C2H4O2/c1-11-15-7-13(22)4-5-14(15)21(29)27(2)10-16-19(17(8-23)28(3)26-16)12-6-18(30-11)20(24)25-9-12;1-2(3)4/h4-7,9,11H,10H2,1-3H3,(H2,24,25);1H3,(H,3,4)/t11-;/m1./s1
Molecular Formula | C21H19FN6O2 |
Molecular Weight | 406.413 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Molecular Formula | C2H4O2 |
Molecular Weight | 60.052 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including:
http://adisinsight.springer.com/drugs/800039198 | http://meetinglibrary.asco.org/content/143329-156
Curator's Comment: description was created based on several sources, including:
http://adisinsight.springer.com/drugs/800039198 | http://meetinglibrary.asco.org/content/143329-156
Lorlatinib is an investigational medicine that inhibits the anaplastic lymphoma kinase (ALK) and ROS1 proto-oncogene. Lorlatinib was specifically designed to inhibit tumor mutations that drive resistance to other ALK inhibitors. Lorlatinib has in vitro activity against ALK and number of other tyrosine kinase receptor related targets including ROS1, TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK. Lorlatinib demonstrated in vitro activity against multiple mutant forms of the ALK enzyme, including some mutations detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors. Moreover, lorlatinib possesses the capability to cross the blood-brain barrier, allowing it to reach and treat progressive or worsening brain metastases as well. Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) indicated for the treatment of patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on a) the prior use of crizotinib and at least one other ALK inhibitor for metastatic disease, or b) the prior use of alectinib as the first ALK inhibitor therapy for metastatic disease, or c) the prior use of certinib as the first ALK inhibitor therapy for metastatic disease.
Originator
Sources: http://adisinsight.springer.com/drugs/800039198
Curator's Comment: # Pfizer
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
0.07 nM [IC50] | |||
0.02 nM [IC50] | |||
Target ID: CHEMBL5627 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24819116 |
2.7 nM [IC50] | ||
Target ID: CHEMBL3982 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24819116 |
3.3 nM [IC50] | ||
Target ID: CHEMBL5455 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24819116 |
6.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Lorbrena Approved UseLORBRENA
is a kinase inhibitor indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on
crizotinib and at least one other ALK inhibitor for metastatic disease; or
alectinib as the first ALK inhibitor therapy for metastatic disease; or
ceritinib as the first ALK inhibitor therapy for metastatic disease
. Launch Date2018 |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
577 ng/mL |
100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LORLATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5650 ng × h/mL |
100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LORLATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
24 h |
100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LORLATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
34% |
100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LORLATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
200 mg 1 times / day multiple, oral Highest studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 51 years n = 3 Health Status: unhealthy Age Group: 51 years Sex: M+F Population Size: 3 Sources: |
Disc. AE: Cognitive disorder, Aphasia... AEs leading to discontinuation/dose reduction: Cognitive disorder (2 patients) Sources: Aphasia (2 patients) Irritability (2 patients) |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Disc. AE: Respiratory failure, Dyspnea... AEs leading to discontinuation/dose reduction: Respiratory failure (1.4%) Sources: Dyspnea (0.7%) Myocardial infarction (0.7%) Cognitive disorder NEC (0.7%) Mood disorder (0.7%) Edema (7%) Hypertriglyceridemia (6%) Peripheral neuropathy (5%) Cognitive disorder NEC (4.4%) Lipase increased (3.7%) Hypercholesterolemia (3.4%) Mood disorder (3.1%) Dyspnea (2.7%) Pneumonia (2.7%) Hypertension (2%) Edema (6%) Peripheral neuropathy (4.7%) Cognitive disorder NEC (4.1%) Mood disorder (3.1%) |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Disc. AE: Acute leukemia, Brain compression... AEs leading to discontinuation/dose reduction: Acute leukemia (0.3%) Sources: Page: p. 164Brain compression (0.3%) Embolism (0.3%) Hallucinations (0.3%) Headache (0.3%) Hydrocephalus (0.3%) Hypoxia (0.3%) Leukocytosis (0.3%) Loss of consciousness (0.3%) Lung infection (0.3%) Mental status changes (0.3%) Parkinsonian gait (0.3%) Peripheral swelling (0.3%) Thrombocytopenia (0.3%) Tinnitus (0.3%) Vomiting (0.3%) Hypertriglyceridemia (1.7%) Arthralgia (1%) Dizziness (1%) Hallucinations (1%) Weight increased (1%) Blood amylase increased (1.7%) Diarrhea (1.7%) Fatigue (1.7%) Asthenia (1.7%) Dizziness (1.4%) Fall (1.4%) Hyperglycemia (1.4%) Pyrexia (1.4%) ALT increased (1%) Anemia (1%) Arthralgia (1%) Atrial fibrillation (1%) Back pain (1%) Ejection fraction decreased (1%) Mental status changes (1%) Pericardial effusion (1%) Pleural effusion (1%) Acute respiratory failure (1%) Respiratory failure (1%) Vomiting (1%) Weight increased (1%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Aphasia | 2 patients Disc. AE |
200 mg 1 times / day multiple, oral Highest studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 51 years n = 3 Health Status: unhealthy Age Group: 51 years Sex: M+F Population Size: 3 Sources: |
Cognitive disorder | 2 patients Disc. AE |
200 mg 1 times / day multiple, oral Highest studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 51 years n = 3 Health Status: unhealthy Age Group: 51 years Sex: M+F Population Size: 3 Sources: |
Irritability | 2 patients Disc. AE |
200 mg 1 times / day multiple, oral Highest studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy, 51 years n = 3 Health Status: unhealthy Age Group: 51 years Sex: M+F Population Size: 3 Sources: |
Cognitive disorder NEC | 0.7% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Dyspnea | 0.7% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Mood disorder | 0.7% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Myocardial infarction | 0.7% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Respiratory failure | 1.4% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Hypertension | 2% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Dyspnea | 2.7% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Pneumonia | 2.7% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Mood disorder | 3.1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Mood disorder | 3.1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Hypercholesterolemia | 3.4% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Lipase increased | 3.7% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Cognitive disorder NEC | 4.1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Cognitive disorder NEC | 4.4% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Peripheral neuropathy | 4.7% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Peripheral neuropathy | 5% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Edema | 6% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Hypertriglyceridemia | 6% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Edema | 7% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: |
Acute leukemia | 0.3% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Brain compression | 0.3% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Embolism | 0.3% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Hallucinations | 0.3% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Headache | 0.3% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Hydrocephalus | 0.3% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Hypoxia | 0.3% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Leukocytosis | 0.3% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Loss of consciousness | 0.3% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Lung infection | 0.3% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Mental status changes | 0.3% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Parkinsonian gait | 0.3% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Peripheral swelling | 0.3% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Thrombocytopenia | 0.3% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Tinnitus | 0.3% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Vomiting | 0.3% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
ALT increased | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Acute respiratory failure | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Anemia | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Arthralgia | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Arthralgia | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Atrial fibrillation | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Back pain | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Dizziness | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Ejection fraction decreased | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Hallucinations | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Mental status changes | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Pericardial effusion | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Pleural effusion | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Respiratory failure | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Vomiting | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Weight increased | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Weight increased | 1% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Dizziness | 1.4% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Fall | 1.4% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Hyperglycemia | 1.4% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Pyrexia | 1.4% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Asthenia | 1.7% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Blood amylase increased | 1.7% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Diarrhea | 1.7% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Fatigue | 1.7% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Hypertriglyceridemia | 1.7% Disc. AE |
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: Page: p. 164 |
unhealthy, 53 years (range: 19 - 85 years) n = 295 Health Status: unhealthy Condition: non-small cell lung cancer (NSCLC) Age Group: 53 years (range: 19 - 85 years) Sex: M+F Population Size: 295 Sources: Page: p. 164 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf Page: 85.0 |
yes [EC50 2.85 uM] | yes (co-administration study) Comment: rifampin reduced mean lorlatinib AUC by 85% and Cmax by 76% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf Page: 85.0 |
||
Page: 14.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf Page: 85.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf Page: 85.0 |
yes | |||
Page: 14.0 |
yes | |||
Page: 14.0 |
yes | |||
Page: 14.0 |
yes | |||
Page: 14.0 |
yes | |||
Page: 14.0 |
yes | yes (co-administration study) Comment: lorlatinib reduced midazolam AUC by 64% and Cmax by 50% Page: 14.0 |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 13.0 |
minor | |||
Page: 13.0 |
minor | |||
Page: 13.0 |
minor | |||
Page: 13.0 |
minor | |||
Page: 13.0 |
yes | |||
Page: 13, 14 |
yes | yes (co-administration study) Comment: rifampin reduced mean lorlatinib AUC by 85% and Cmax by 76%; Itraconazole increased lorlatinib AUC by 42% and Cmax by 24% Page: 13, 14 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf Page: 42, 49 |
||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210868Orig1s000MultidisciplineR.pdf Page: 42, 51 |
PubMed
Title | Date | PubMed |
---|---|---|
Tackling ALK in non-small cell lung cancer: the role of novel inhibitors. | 2016 Jun |
|
Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer. | 2016 Oct |
|
The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma driven by expression of ALK and MYCN. | 2016 Sep 1 |
Patents
Sample Use Guides
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27483357
Mutant ALKG1128A, ALKF1174L, ALKR1192P, ALKF1245C and ALKR1275Q responded to PF-06463922 with IC50 values similar to that of wild-type, two mutants – ALKI1171N and ALKY1278S – were more resistant, with 4- and 2.8-fold (3.21 nM and 2.27 nM) respectively of the IC50 of wild-type ALK kinase.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 15:07:43 GMT 2023
by
admin
on
Sat Dec 16 15:07:43 GMT 2023
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Record UNII |
TE9WI16FEU
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Record Status |
Validated (UNII)
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Record Version |
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TE9WI16FEU
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1924207-18-0
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124203822
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