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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H19FN6O2
Molecular Weight 406.4138
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LORLATINIB

SMILES

C[C@]1([H])c2cc(ccc2C(=O)N(C)Cc3c(-c4cc(c(N)nc4)O1)c(C#N)n(C)n3)F

InChI

InChIKey=IIXWYSCJSQVBQM-LLVKDONJSA-N
InChI=1S/C21H19FN6O2/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/h4-7,9,11H,10H2,1-3H3,(H2,24,25)/t11-/m1/s1

HIDE SMILES / InChI

Molecular Formula C21H19FN6O2
Molecular Weight 406.4138
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

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

Curator's Comment:: # Pfizer

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Primary
Lorbrena

Approved Use

LORBRENA 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 Date

1541116800000
Primary
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Funbound

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse 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
Health Status: unhealthy
Age Group: 51 years
Sex: M+F
Sources:
Disc. AE: Cognitive disorder, Aphasia...
AEs leading to
discontinuation/dose reduction:
Cognitive disorder (2 patients)
Aphasia (2 patients)
Irritability (2 patients)
Sources:
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
Disc. AE: Respiratory failure, Dyspnea...
AEs leading to
discontinuation/dose reduction:
Respiratory failure (1.4%)
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%)
Sources:
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
Disc. AE: Acute leukemia, Brain compression...
AEs leading to
discontinuation/dose reduction:
Acute leukemia (0.3%)
Brain 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%)
Sources:
AEs

AEs

AESignificanceDosePopulation
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
Health Status: unhealthy
Age Group: 51 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 51 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 51 years
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
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:
unhealthy, 53 years (range: 19 - 85 years)
Health Status: unhealthy
Age Group: 53 years (range: 19 - 85 years)
Sex: M+F
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
yes [EC50 2.85 uM]
yes (co-administration study)
Comment: rifampin reduced mean lorlatinib AUC by 85% and Cmax by 76%
Page: 85
yes
yes
yes
yes
yes
yes
yes
yes
yes (co-administration study)
Comment: lorlatinib reduced midazolam AUC by 64% and Cmax by 50%
Page: 14
Drug as victimTox targets
PubMed

PubMed

TitleDatePubMed
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

The recommended dosage is 100 mg orally once daily.
Route of Administration: Oral
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 Sat Jun 26 11:09:33 UTC 2021
Edited
by admin
on Sat Jun 26 11:09:33 UTC 2021
Record UNII
OSP71S83EU
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LORLATINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
LORBRENA
Brand Name English
LORLATINIB [WHO-DD]
Common Name English
PF-06463922
Code English
LORLATINIB [INN]
Common Name English
(10R)-7-AMINO-12-FLUORO-2,10,16-TRIMETHYL-15-OXO-10,15,16,17-TETRAHYDRO-2H-4,8- METHENOPYRAZOLO(4,3-H)(2,5,11)BENZOXADIAZACYCLOTETRADECINE-3-CARBONITRILE
Systematic Name English
LORLATINIB [USAN]
Common Name English
2H-4,8-METHENOPYRAZOLO(4,3-H)(2,5,11)BENZOXADIAZACYCLOTETRADECINE-3-CARBONITRILE, 7-AMINO-12-FLUORO-10,15,16,17-TETRAHYDRO-2,10,16-TRIMETHYL-15-OXO-, (10R)-
Systematic Name English
LORLATINIB [MI]
Common Name English
LORLATINIB [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C141136
Created by admin on Sat Jun 26 11:09:34 UTC 2021 , Edited by admin on Sat Jun 26 11:09:34 UTC 2021
FDA ORPHAN DRUG 481015
Created by admin on Sat Jun 26 11:09:34 UTC 2021 , Edited by admin on Sat Jun 26 11:09:34 UTC 2021
WHO-ATC L01XE44
Created by admin on Sat Jun 26 11:09:34 UTC 2021 , Edited by admin on Sat Jun 26 11:09:34 UTC 2021
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 11:09:34 UTC 2021 , Edited by admin on Sat Jun 26 11:09:34 UTC 2021
Code System Code Type Description
CAS
1454846-35-5
Created by admin on Sat Jun 26 11:09:34 UTC 2021 , Edited by admin on Sat Jun 26 11:09:34 UTC 2021
PRIMARY
NCI_THESAURUS
C113655
Created by admin on Sat Jun 26 11:09:34 UTC 2021 , Edited by admin on Sat Jun 26 11:09:34 UTC 2021
PRIMARY
DRUG BANK
DB12130
Created by admin on Sat Jun 26 11:09:34 UTC 2021 , Edited by admin on Sat Jun 26 11:09:34 UTC 2021
PRIMARY
INN
10278
Created by admin on Sat Jun 26 11:09:34 UTC 2021 , Edited by admin on Sat Jun 26 11:09:34 UTC 2021
PRIMARY
DRUG CENTRAL
5302
Created by admin on Sat Jun 26 11:09:34 UTC 2021 , Edited by admin on Sat Jun 26 11:09:34 UTC 2021
PRIMARY
PUBCHEM
71731823
Created by admin on Sat Jun 26 11:09:34 UTC 2021 , Edited by admin on Sat Jun 26 11:09:34 UTC 2021
PRIMARY
MERCK INDEX
M12113
Created by admin on Sat Jun 26 11:09:34 UTC 2021 , Edited by admin on Sat Jun 26 11:09:34 UTC 2021
PRIMARY
LACTMED
Lorlatinib
Created by admin on Sat Jun 26 11:09:34 UTC 2021 , Edited by admin on Sat Jun 26 11:09:34 UTC 2021
PRIMARY
RXCUI
2103164
Created by admin on Sat Jun 26 11:09:34 UTC 2021 , Edited by admin on Sat Jun 26 11:09:34 UTC 2021
PRIMARY
ChEMBL
CHEMBL3286830
Created by admin on Sat Jun 26 11:09:34 UTC 2021 , Edited by admin on Sat Jun 26 11:09:34 UTC 2021
PRIMARY
FDA UNII
OSP71S83EU
Created by admin on Sat Jun 26 11:09:34 UTC 2021 , Edited by admin on Sat Jun 26 11:09:34 UTC 2021
PRIMARY
EVMPD
SUB181272
Created by admin on Sat Jun 26 11:09:34 UTC 2021 , Edited by admin on Sat Jun 26 11:09:34 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
MINOR
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
TARGET -> INHIBITOR
Ki
METABOLIC ENZYME -> SUBSTRATE
MAJOR
METABOLIC ENZYME -> SUBSTRATE
MAJOR
BINDER->LIGAND
In vitro, protein binding of lorlatinib to human plasma proteins, including serum albumin and ?1-acid glycoprotein, was 66% at a concentration of 2.4 ?M.
BINDING
TARGET -> INHIBITOR
INHIBITOR
IC50
METABOLIC ENZYME -> INDUCER
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
Ki
TARGET -> INHIBITOR
Ki
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
OFF TARGET->NON-INHIBITOR
did not predict QTc prolongation, by inhibition of the hERG channel at clinically relevant concentrations
METABOLIC ENZYME -> SUBSTRATE
MINOR
TRANSPORTER -> INHIBITOR
OFF TARGET->NON-INHIBITOR
failed to inhibit L-type calcium channel, or Nav1.5 sodium current at clinically relevant concentrations.
METABOLIC ENZYME -> INDUCER
ACTIVATOR
TARGET -> INHIBITOR
Ki
METABOLIC ENZYME -> SUBSTRATE
MINOR
TARGET -> INHIBITOR
Ki
TARGET -> INHIBITOR
Ki
METABOLIC ENZYME -> SUBSTRATE
MINOR
EXCRETED UNCHANGED
Following a single oral 100 mg dose of radiolabeled lorlatinib, 48% of the radioactivity was recovered in urine (< 1% as unchanged) and 41% in feces (about 9% as unchanged).
FECAL; URINE
TARGET -> INHIBITOR
Ki
METABOLIC ENZYME -> INHIBITOR
TIME-DEPENDENT INHIBITION
Ki
TARGET -> INHIBITOR
Ki
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Cmax PHARMACOKINETIC ROUTE OF ADMINSTRATION
PHARMACOKINETIC
DOSE
PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC SINGLE DOSE

ORAL

Blood-to-plasma ratio PHARMACOKINETIC
Tmax PHARMACOKINETIC SINGLE DOSE

ORAL

Biological Half-life PHARMACOKINETIC SINGLE DOSE

INTRAVENOUS

Volume of Distribution PHARMACOKINETIC SINGLE DOSE

INTRAVENOUS