Abemaciclib

Details

Stereochemistry	ACHIRAL
Molecular Formula	C27H32F2N8
Molecular Weight	506.5934
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN1CCN(CC2=CN=C(NC3=NC=C(F)C(=N3)C4=CC5=C(N=C(C)N5C(C)C)C(F)=C4)C=C2)CC1

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	506.5934
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27217383
Curator's Comment: description was created based on several sources, including 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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclin-dependent kinase 6 16 Target ID: CHEMBL2508 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24919854	Inhibitor 8504		10.0 nM [IC50]
Cyclin-dependent kinase 4 26 Target ID: CHEMBL331 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24919854	Inhibitor 8504		2.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
HER2-negative advanced breast cancer 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208716Orig1s000lbl.pdf	Primary	Approved 8583	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 2017
Breast cancer 432 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27493615	Primary	Phase III 665	Unknown Approved Use Unknown
Non-small cell lung cancer 211 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27217383	Primary	Phase III 665	Unknown Approved Use Unknown
Glioblastoma 66 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27217383	Primary	Phase II 1147	Unknown Approved Use Unknown
Melanoma 88 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27217383	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
226 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	100 mg 2 times / day steady-state, oral dose: 100 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
58.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	75 mg 2 times / day steady-state, oral dose: 75 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
102 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	100 mg 1 times / day steady-state, oral dose: 100 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
246 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	275 mg single, oral dose: 275 mg route of administration: Oral experiment type: SINGLE co-administered:	ABEMACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
158 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	ABEMACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
114 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	ABEMACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
39.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	ABEMACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
298 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	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

Value	Dose	Analyte	Population
2250 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	100 mg 2 times / day steady-state, oral dose: 100 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
546 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	75 mg 2 times / day steady-state, oral dose: 75 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
1840 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	100 mg 1 times / day steady-state, oral dose: 100 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
7890 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	275 mg single, oral dose: 275 mg route of administration: Oral experiment type: SINGLE co-administered:	ABEMACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5220 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	ABEMACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4010 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	ABEMACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1270 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	ABEMACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3000 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02152631	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:

T_1/2

Value	Dose	Analyte	Population
25 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	275 mg single, oral dose: 275 mg route of administration: Oral experiment type: SINGLE co-administered:	ABEMACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	ABEMACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
22.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	ABEMACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
25.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27217383/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	ABEMACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
3.7% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208716s000lbl.pdf			ABEMACICLIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/27217383	unhealthy, 44-66 years Health Status: unhealthy Age Group: 44-66 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/27217383	DLT: Fatigue... Dose limiting toxicities: Fatigue (grade 3, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/27217383
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: https://pubmed.ncbi.nlm.nih.gov/27217383	unhealthy, 51-68 years Health Status: unhealthy Age Group: 51-68 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/27217383	DLT: Fatigue... Dose limiting toxicities: Fatigue (grade 3, 7 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/27217383
600 mg single, oral Highest studied dose Dose: 600 mg Route: oral Route: single Dose: 600 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000MultidisciplineR.pdf	healthy Health Status: healthy Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000MultidisciplineR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000MultidisciplineR.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208855s000lbl.pdf	unhealthy Health Status: unhealthy Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208855s000lbl.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208855s000lbl.pdf
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: https://pubmed.ncbi.nlm.nih.gov/27312735	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/27312735	DLT: Nausea... Dose limiting toxicities: Nausea (grade 2, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/27312735

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252 supressor 22	inhibitor 2438 supressor 19	inhibitor 2507 inducer 109	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 BCRP 910 OCT2 779 MATE1 415 MATE2 267 CYP1A2 2153 CYP2B6 926 CYP2C8 1057 CYP2C19 2057	CYP3A4/5 91

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes Page: -	no
CYP2B6 1160	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes Page: -	no
CYP2C19 2141	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes Page: -	no
CYP2C8 1117	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes Page: -	no
CYP2C9 2497	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes Page: -	no
CYP2D6 2546	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes Page: -	no
CYP3A4 2633	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes Page: -	no
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000MultidisciplineR.pdf#page=82 Page: 82.0	yes [IC50 0.32 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000MultidisciplineR.pdf#page=82 Page: 82.0	yes [IC50 0.57 uM]
CYP2B6 1160	supressor 160 Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes Page: -	yes
CYP1A2 2333	supressor 160 Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes 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. Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes Page: -
CYP2C9 2497	supressor 160 Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes 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. Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes Page: -
CYP2D6 2546	inducer 1966 Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes 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. Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes Page: -
CYP3A4 2633	supressor 160 Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes 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. Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes Page: -
CYP3A5 201	supressor 160 Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes 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. Sources: https://dmd.aspetjournals.org/content/dmd/48/9/796.full.pdf?with-ds=yes Page: -
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000MultidisciplineR.pdf#page=82 Page: 82.0	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000MultidisciplineR.pdf#page=82 Page: 82.0
MATE2 267	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000MultidisciplineR.pdf#page=82 Page: 82.0	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000MultidisciplineR.pdf#page=82 Page: 82.0
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000MultidisciplineR.pdf#page=82 Page: 82.0	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000MultidisciplineR.pdf#page=82 Page: 82.0

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4/5 91	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000MultidisciplineR.pdf#page=81 Page: 81.0	yes
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000MultidisciplineR.pdf#page=76 Page: 76.0	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000MultidisciplineR.pdf#page=76 Page: 76.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000MultidisciplineR.pdf#page=45 Page: 45.0

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY513223	https://www.001chemical.com/chem/1231929-97-7
AA Blocks	AA000K2I	https://www.aablocks.com/goods/Goods/detail?id=AA000K2I
Aaron Chemicals	AR000KUA	http://www.aaronchem.com/1231929-97-7
abcr GmbH	AB456700	http://www.abcr.com/shop/en/AB456700
Achemtek	0102-014357	http://www.achemtek.com/1231929-97-7
Acorn PharmaTech	ACN-050731	http://www.acornpharmatech.com/
Adooq BioScience	A12989	https://www.adooq.com/ly2835219.html
AK Scientific, Inc. (AKSCI)	3798AH	http://www.aksci.com/item_detail.php?cat=3798AH
Alsachim	4676	http://www.alsachim.com/product-C6024-glo.bal-view.html
Ambinter	Amb24088162	http://www.ambinter.com/reference/24088162
Angene	AGN-PC-0WCXV5	http://www.angenechemical.com/productshow/AGN-PC-0WCXV5.html
Ark Pharm	AK174895	http://www.arkpharminc.com/products/1231929-97-7.html
Aurum Pharmatech LLC	W-5974	http://www.Aurumpharmatech.com/Product/ProductDetails/W_5974
BioChemPartner	BCP13079	http://www.biochempartner.com/1231929-97-7-BCP13079
BioCrick	BCC1722	http://www.biocrick.com/LY2835219-free-base-BCC1722.html
BioSynth	J-690083	https://www.biosynth.com/en/products/all-products/products/J-690100.html
BOC Sciences	1231929-97-7	https://www.bocsci.com/abemaciclib-cas-1231929-97-7-item-462724.html
Chem Scene	CS-1230	http://www.chemscene.com/1231929-97-7.html
ChemFish Tokyo co.,ltd	46220502	http://www.chemfish.co.jp/index.php?id=4625&project=product
ChemieTek	CT-LY283	http://www.chemietek.com/ly2835219--abemaciclib---free-base-details.aspx
Chemspace	CSSB00020639774	https://chem-space.com/CSSB00020639774
Clearsynth	CS-CX-00032	https://www.clearsynth.com/en/CSCX00032.html
DC Chemicals	DC8643	http://www.dcchemicals.com/product_show-LY2835219_free_base_Abemaciclib_.html
Debye Scientific	DA-33422	http://www.debyesci.com/cas_1231929-97-7.html
eNovation Chemicals	D570922	https://www.enovationchem.com/ProductDetails.asp?ProductID=D570922
Excenen	EX-A1588	http://www.excenen.com/searchresultlist.php?id=1231930-82-7
Excenen	EX-A521	http://www.excenen.com/searchresultlist.php?id=1231929-97-7
Finetech	FT-0700134	http://www.finetechnology-ind.com/prod/detail/pub/1231929-97-7.html
Hairui	ABSA049	http://www.hairuichem.com/en/product/1231929-97-7.html
iChemical	EBD3328775	http://www.ichemical.com/products/1231929-97-7.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
Lab Network	LN01341896	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01341896
Lancrix Chemicals	878262	http://www.lancrix.com/product/detail-14-1388.htm
MedChem Express	HY-16297A	https://www.medchemexpress.com/LY2835219-free-base.html
Molcore	MC513223	https://www.molcore.com/product/1231929-97-7
MolPort	MolPort-039-137-732	https://www.molport.com/shop/molecule-link/MolPort-039-137-732
MuseChem	I000911	https://www.musechem.com/product/I000911.html
Nextpeptide	NP185851	http://www.nextpeptide.com/1231929-97-7.html
Shanghai Send Pharmaceutical Technology Co., Ltd	send21142	http://shsendpharm.com/
Smolecule	S516742	http://www.smolecule.com/products/s516742
Sun-shine Chemical	Abemaciclib	http://www.sun-shinechem.com/1231929-97-7%28free%20base%29%EF%BC%9B1231930-82-7%28salt%20form%29.html
Synblock Inc	SB16476	http://www.synblock.com/product/1231929-97-7.html
THE BioTek	bt-253313	https://www.thebiotek.com/product/inhibitors/bt-253313
THE BioTek	bt-258068	https://www.thebiotek.com/product/inhibitors/bt-258068
TubePharm	Tube014	http://www.tubepharm.com/product/1231929-97-7,1231930-82-7-en.html
Yuhao Chemical	YH66000	http://www.chemyuhao.com/1231929-97-7.html

PubMed

Title	Date	PubMed
The landscape of somatic copy-number alteration across human cancers.	2010 Feb 18	20164920
A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma.	2010 Jul 13	20609353
Therapeutic response to CDK4/6 inhibition in breast cancer defined by ex vivo analyses of human tumors.	2012 Jul 15	22767154
Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia.	2012 Oct 16	23079656
The requirement for cyclin D function in tumor maintenance.	2012 Oct 16	23079655
A CDK4/6 inhibitor enhances cytotoxicity of paclitaxel in lung adenocarcinoma cells harboring mutant KRAS as well as wild-type KRAS.	2013 Jul	23792647
Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine.	2014 Oct	24919854

Patents

Sample Use Guides

In Vivo Use Guide

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). non-small cell lung cancer: 200 milligrams (mg) abemaciclib administered, orally, every 12 hours plus best supportive care (BSC) on Days 1 to 28 (28 day cycles).

Route of Administration: Oral

In Vitro Use Guide

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 `Mon Mar 31 22:37:13 GMT 2025` Edited by `admin` on `Mon Mar 31 22:37:13 GMT 2025`
Record UNII	60UAB198HK
Record Status	`Validated (UNII)`
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Name

Type

Language

Abemaciclib

Official Name

English

Abemaciclib [INN]

Preferred Name

English

Abemaciclib [WHO-DD]

Common Name

English

LY-2835210

Code

English

Abemaciclib [JAN]

Common Name

English

Verzenio

Brand Name

English

LY2835210

Code

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 [ORANGE BOOK]

Common Name

English

N-(5-((4-ethylpiperazin-1-yl)methyl)pyridin-2-yl)-5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-amine

Systematic Name

English

N-[5-[(4-Ethyl-1-piperazinyl)methyl]-2-pyridinyl]-5-fluoro-4-[4-fluoro-2-methyl-1-(1-methylethyl)-1H-benzimidazol-6-yl]-2-pyrimidinamine

Systematic Name

English

Abemaciclib [USAN]

Common Name

English

Abemaciclib [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C129825