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Details

Stereochemistry ACHIRAL
Molecular Formula C27H32F2N8
Molecular Weight 506.5944
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ABEMACICLIB

SMILES

CCN1CCN(CC1)Cc2ccc(nc2)Nc3ncc(c(-c4cc(c5c(c4)n(C(C)C)c(C)n5)F)n3)F

InChI

InChIKey=UZWDCWONPYILKI-UHFFFAOYSA-N
InChI=1S/C27H32F2N8/c1-5-35-8-10-36(11-9-35)16-19-6-7-24(30-14-19)33-27-31-15-22(29)25(34-27)20-12-21(28)26-23(13-20)37(17(2)3)18(4)32-26/h6-7,12-15,17H,5,8-11,16H2,1-4H3,(H,30,31,33,34)

HIDE SMILES / InChI

Molecular Formula C27H32F2N8
Molecular Weight 506.5944
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: https://www.ncbi.nlm.nih.gov/pubmed/24919854

Abemaciclib, previously known as LY2835219, is a potent and selective inhibitor of cyclin-dependent kinases: CDK4 and CDK6, developed by Eli Lilly, which is in clinical trial phase III for the treatment of breast cancer and non-small cell lung cancer (NSCLC) and in phase II for investigation of its treatment glioblastoma and melanoma.

CNS Activity

Curator's Comment:: Known to be CNS penetrant in mouse. Human data not available

Originator

Curator's Comment:: # Eli Lilly

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
10 nM [IC50]
2 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
VERZENIO

Approved Use

in combination with fulvestrant for the treatment of women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. As monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

Launch Date

1506470400000
Primary
Primary
Primary
Primary
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
298 ng/mL
200 mg 2 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ABEMACICLIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
5520 ng × h/mL
200 mg 2 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ABEMACICLIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3350 ng*h/mL
200 mg 2 times / day steady, oral
dose: 200 mg
route of administration: oral
experiment type: steady
co-administered:
ABEMACICLIB plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
17.4 h
200 mg 2 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ABEMACICLIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
3.7%
ABEMACICLIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
275 mg 2 times / day steady, oral
Highest studied dose
Dose: 275 mg, 2 times / day
Route: oral
Route: steady
Dose: 275 mg, 2 times / day
Sources:
unhealthy, 44-66 years
Health Status: unhealthy
Age Group: 44-66 years
Sex: F
Sources:
DLT: Fatigue...
Dose limiting toxicities:
Fatigue (grade 3, 2 patients)
Sources:
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy, 51-68 years
Health Status: unhealthy
Age Group: 51-68 years
Sex: M+F
Sources:
DLT: Fatigue...
Dose limiting toxicities:
Fatigue (grade 3, 7 patients)
Sources:
600 mg single, oral
Highest studied dose
healthy
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Disc. AE: Diarrhea, Diarrhea...
Other AEs: Diarrhea, Nausea...
AEs leading to
discontinuation/dose reduction:
Diarrhea (grade 3, 20%)
Diarrhea (20%)
Infection (grade 5, 2%)
Fatigue (9%)
Other AEs:
Diarrhea (grade 1-2, 70%)
Nausea (grade 1-2, 59%)
Nausea (grade 3, 5%)
Abdominal pain (grade 1-2, 37%)
Abdominal pain (grade 3, 2%)
Vomiting (grade 1-2, 33%)
Vomiting (grade 3, 2%)
Constipation (grade 1-2, 16%)
Constipation (grade 3, <1%)
Dry mouth (grade 1-2, 14%)
Stomatitis (grade 1-2, 14%)
Infection (grade 1-2, 26%)
Stomatitis (grade 3, 5%)
Asthenia (grade 1-2, 52%)
Fatigue (grade 1-2, 52%)
Asthenia (grade 3, 13%)
Fatigue (grade 3, 13%)
Pyrexia (grade 1-2, 11%)
Neutropenia (grade 1-2, 13%)
Neutropenia (grade 3, 19%)
Neutropenia (grade 4, 5%)
Neutrophil count decreased (grade 1-2, 13%)
Neutrophil count decreased (grade 3, 19%)
Neutrophil count decreased (grade 4, 5%)
Anemia (grade 1-2, 20%)
Hematocrit decreased (grade 1-2, 20%)
Hemoglobin decreased (grade 1-2, 20%)
Red blood cell count decreased (grade 1-2, 20%)
Anemia (grade 3, 5%)
Hematocrit decreased (grade 3, 5%)
Hemoglobin decreased (grade 3, 5%)
Red blood cell count decreased (grade 3, 5%)
Platelet count decreased (grade 1-2, 16%)
Thrombocytopenia (grade 1-2, 16%)
Platelet count decreased (grade 3, 4%)
Thrombocytopenia (grade 3, 4%)
Leukopenia (grade 1-2, 11%)
White blood cell count decreased (grade 1-2, 11%)
Leukopenia (grade 3, 5%)
White blood cell count decreased (grade 3, 5%)
Leukopenia (grade 4, <1%)
White blood cell count decreased (grade 4, <1%)
Decreased appetite (grade 1-2, 42%)
Decreased appetite (grade 3, 3%)
Dehydration (grade 1-2, 8%)
Dehydration (grade 3, 2%)
Cough (grade 1-2, 19%)
Arthralgia (grade 1-2, 15%)
Headache (grade 1-2, 20%)
Dysgeusia (grade 1-2, 12%)
Dizziness (grade 1-2, 11%)
Alopecia (grade 1-2, 12%)
Creatinine increased (grade 1-2, 12%)
Creatinine increased (grade 3, <1%)
Weight decreased (grade 1-2, 14%)
White blood cell decreased (grade 1-2, 97%)
White blood cell decreased (grade 3, <1%)
Neutrophil count decreased (grade 1-2, 63%)
Neutrophil count decreased (grade 3, 28%)
Anemia (grade 1-2, 68%)
Lymphocyte count decreased (grade 1-2, 28%)
Lymphocyte count decreased (grade 3, 13%)
Lymphocyte count decreased (grade 4, <1%)
ALT increased (grade 1-2, 28%)
ALT increased (grade 3, 3%)
AST increased (grade 1-2, 26%)
AST increased (grade 3, 4%)
Sources:
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
DLT: Nausea...
Dose limiting toxicities:
Nausea (grade 2, 1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Fatigue grade 3, 2 patients
DLT
275 mg 2 times / day steady, oral
Highest studied dose
Dose: 275 mg, 2 times / day
Route: oral
Route: steady
Dose: 275 mg, 2 times / day
Sources:
unhealthy, 44-66 years
Health Status: unhealthy
Age Group: 44-66 years
Sex: F
Sources:
Fatigue grade 3, 7 patients
DLT
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy, 51-68 years
Health Status: unhealthy
Age Group: 51-68 years
Sex: M+F
Sources:
Diarrhea 20%
Disc. AE
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Fatigue 9%
Disc. AE
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Dizziness grade 1-2, 11%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Leukopenia grade 1-2, 11%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Pyrexia grade 1-2, 11%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
White blood cell count decreased grade 1-2, 11%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Alopecia grade 1-2, 12%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Creatinine increased grade 1-2, 12%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Dysgeusia grade 1-2, 12%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Neutropenia grade 1-2, 13%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Neutrophil count decreased grade 1-2, 13%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Dry mouth grade 1-2, 14%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Stomatitis grade 1-2, 14%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Weight decreased grade 1-2, 14%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Arthralgia grade 1-2, 15%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Constipation grade 1-2, 16%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Platelet count decreased grade 1-2, 16%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Thrombocytopenia grade 1-2, 16%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Cough grade 1-2, 19%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Anemia grade 1-2, 20%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Headache grade 1-2, 20%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Hematocrit decreased grade 1-2, 20%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Hemoglobin decreased grade 1-2, 20%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Red blood cell count decreased grade 1-2, 20%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
AST increased grade 1-2, 26%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Infection grade 1-2, 26%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
ALT increased grade 1-2, 28%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Lymphocyte count decreased grade 1-2, 28%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Vomiting grade 1-2, 33%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Abdominal pain grade 1-2, 37%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Decreased appetite grade 1-2, 42%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Asthenia grade 1-2, 52%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Fatigue grade 1-2, 52%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Nausea grade 1-2, 59%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Neutrophil count decreased grade 1-2, 63%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Anemia grade 1-2, 68%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Diarrhea grade 1-2, 70%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Dehydration grade 1-2, 8%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
White blood cell decreased grade 1-2, 97%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Asthenia grade 3, 13%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Fatigue grade 3, 13%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Lymphocyte count decreased grade 3, 13%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Neutropenia grade 3, 19%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Neutrophil count decreased grade 3, 19%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Abdominal pain grade 3, 2%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Dehydration grade 3, 2%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Vomiting grade 3, 2%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Diarrhea grade 3, 20%
Disc. AE
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Neutrophil count decreased grade 3, 28%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
ALT increased grade 3, 3%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Decreased appetite grade 3, 3%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
AST increased grade 3, 4%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Platelet count decreased grade 3, 4%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Thrombocytopenia grade 3, 4%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Anemia grade 3, 5%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Hematocrit decreased grade 3, 5%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Hemoglobin decreased grade 3, 5%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Leukopenia grade 3, 5%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Nausea grade 3, 5%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Red blood cell count decreased grade 3, 5%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Stomatitis grade 3, 5%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
White blood cell count decreased grade 3, 5%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Constipation grade 3, <1%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Creatinine increased grade 3, <1%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
White blood cell decreased grade 3, <1%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Neutropenia grade 4, 5%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Neutrophil count decreased grade 4, 5%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Leukopenia grade 4, <1%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Lymphocyte count decreased grade 4, <1%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
White blood cell count decreased grade 4, <1%
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Infection grade 5, 2%
Disc. AE
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Nausea grade 2, 1 patient
DLT, Disc. AE
200 mg 2 times / day steady, oral
Recommended|MTD
Dose: 200 mg, 2 times / day
Route: oral
Route: steady
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
Overview

OverviewOther

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
yes [IC50 0.32 uM]
yes [IC50 0.57 uM]
yes
yes
no (co-administration study)
Comment: The downregulation of CYP mRNA expression and activity by abemaciclib in vitro did not translate into the clinic. No clinically relevant changes in the PK of CYP1A2, CYP2C9, CYP2D6, or CYP3A substrate drugs were observed when coadministered with multiple doses of abemaciclib.
Page: -
yes
no (co-administration study)
Comment: The downregulation of CYP mRNA expression and activity by abemaciclib in vitro did not translate into the clinic. No clinically relevant changes in the PK of CYP1A2, CYP2C9, CYP2D6, or CYP3A substrate drugs were observed when coadministered with multiple doses of abemaciclib.
Page: -
yes
no (co-administration study)
Comment: The downregulation of CYP mRNA expression and activity by abemaciclib in vitro did not translate into the clinic. No clinically relevant changes in the PK of CYP1A2, CYP2C9, CYP2D6, or CYP3A substrate drugs were observed when coadministered with multiple doses of abemaciclib.
Page: -
yes
no (co-administration study)
Comment: The downregulation of CYP mRNA expression and activity by abemaciclib in vitro did not translate into the clinic. No clinically relevant changes in the PK of CYP1A2, CYP2C9, CYP2D6, or CYP3A substrate drugs were observed when coadministered with multiple doses of abemaciclib.
Page: -
yes
no (co-administration study)
Comment: The downregulation of CYP mRNA expression and activity by abemaciclib in vitro did not translate into the clinic. No clinically relevant changes in the PK of CYP1A2, CYP2C9, CYP2D6, or CYP3A substrate drugs were observed when coadministered with multiple doses of abemaciclib.
Page: -
yes
yes (co-administration study)
Comment: The renal clearance and active tubular secretion of metformin, a substrate of renal uptake transporter OCT2, and tubular efflux transporters MATE-1 and MATE-2K, was respectively reduced by 45% and 62% following co-administration of a single 400 mg dose of abemaciclib with 1000 mg metformin in healthy subjects.
Page: 82
yes
yes (co-administration study)
Comment: The renal clearance and active tubular secretion of metformin, a substrate of renal uptake transporter OCT2, and tubular efflux transporters MATE-1 and MATE-2K, was respectively reduced by 45% and 62% following co-administration of a single 400 mg dose of abemaciclib with 1000 mg metformin in healthy subjects.
Page: 82
yes
yes (co-administration study)
Comment: The renal clearance and active tubular secretion of metformin, a substrate of renal uptake transporter OCT2, and tubular efflux transporters MATE-1 and MATE-2K, was respectively reduced by 45% and 62% following co-administration of a single 400 mg dose of abemaciclib with 1000 mg metformin in healthy subjects.
Page: 82
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
yes (co-administration study)
Comment: The co-administration of 500 mg twice daily doses of clarithromycin, a strong CYP3A4 inhibitor, with a single 50 mg dose of abemaciclib increased the relative potency adjusted unbound AUC0-INF of abemaciclib plus its active metabolites (M2, M18, and M20) by 1.7-fold relative to abemaciclib alone in cancer patients.
Page: 76
Tox targets

Tox targets

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma.
2010 Jul 13
Therapeutic response to CDK4/6 inhibition in breast cancer defined by ex vivo analyses of human tumors.
2012 Jul 15
The requirement for cyclin D function in tumor maintenance.
2012 Oct 16
Patents

Sample Use Guides

breast cancer: 150 milligrams (mg) Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
Route of Administration: Oral
It was examined the effects of LY2835219 using three head and neck squamous cell carcinoma (HNSCC) cell lines (OSC-19, FaDu, and YD-10B). Cells were treated with LY2835219 at concentrations ranging between 0.01 μM and 10 μM for 72 h. This treatment reduced cell viability at HNSCC cells. The IC50 values for LY2835219 ranged from 0.5 μM to 0.7 μM at HNSCC cells. In addition, LY2835219 inhibited colony formation with long term treatment, indicating that LY2835219 was able to effectively suppress colony formation of HNSCC cells in a dose-dependent manner. OSC-19 cells were treated with 0.1, 0.2, and 0.5 μM LY2835219, and levels of p-AKT (Ser473), p-ERK1/2 (thr202/Tyr204), and p-mTOR (Ser2448) were measured with Western blot analysis. Treatment of cells with LY2835219 inhibited phosphorylation of ERK1/2 and AKT in a dose-dependent manner. Inhibition of AKT by LY2835219 persisted for 48 h after treatment. In contrast, phosphorylation of ERK had recovered at 48 h. Unexpectedly, in spite of inhibition of AKT, LY2835219 had no effect on phosphorylation of mTOR at Ser2448, suggesting continuous activation of mTORC1.
Substance Class Chemical
Created
by admin
on Sat Jun 26 01:57:25 UTC 2021
Edited
by admin
on Sat Jun 26 01:57:25 UTC 2021
Record UNII
60UAB198HK
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ABEMACICLIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
ABEMACICLIB [JAN]
Common Name English
VERZENIO
Brand Name English
ABEMACICLIB [WHO-DD]
Common Name English
LY2835219
Code English
2-PYRIMIDINAMINE, N-(5-((4-ETHYL-1-PIPERAZINYL)METHYL)-2-PYRIDINYL)-5-FLUORO-4-(4-FLUORO-2-METHYL-1-(1-METHYLETHYL)-1H-BENZIMIDAZOL-6-YL)
Systematic Name English
LY-2835219
Code English
ABEMACICLIB [INN]
Common Name English
ABEMACICLIB [ORANGE BOOK]
Common Name English
ABEMACICLIB [USAN]
Common Name English
ABEMACICLIB [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
NDF-RT N0000175605
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
NCI_THESAURUS C2185
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
WHO-ATC L01XE50
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
Code System Code Type Description
RXCUI
1946825
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
PRIMARY
DRUG CENTRAL
5259
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
PRIMARY
NCI_THESAURUS
C97660
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
PRIMARY
ChEMBL
CHEMBL3301610
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
PRIMARY
MERCK INDEX
M12043
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
PRIMARY
INN
10036
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
PRIMARY
EPA CompTox
1231929-97-7
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
PRIMARY
LACTMED
Abemaciclib
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
PRIMARY
DRUG BANK
DB12001
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
PRIMARY
FDA UNII
60UAB198HK
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
PRIMARY
CAS
1231929-97-7
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
PRIMARY
EVMPD
SUB171907
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
PRIMARY
PUBCHEM
46220502
Created by admin on Sat Jun 26 01:57:25 UTC 2021 , Edited by admin on Sat Jun 26 01:57:25 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
IC50
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
TARGET->WEAK INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
TRANSPORTER -> INHIBITOR
IC50
TRANSPORTER -> SUBSTRATE
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
TRANSPORTER -> INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
TRANSPORTER -> SUBSTRATE
CELL->INHIBITOR
SALT/SOLVATE -> PARENT
BINDER->LIGAND
BINDING
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
blood-to-plasma ration PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC