abemaciclib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
cyclin dependant kinase inhibitors 5259 1231929-97-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • abemaciclib
  • LY2835219
  • verzenio
Abemaciclib is an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6). These kinases are activated upon binding to D-cyclins. In estrogen receptor-positive (ER+) breast cancer cell lines, cyclin D1 and CDK4/6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation. In vitro, continuous exposure to abemaciclib inhibited Rb phosphorylation and blocked progression from G1 into S phase of the cell cycle, resulting in senescence and apoptosis. In breast cancer xenograft models, abemaciclib dosed daily without interruption as a single agent or in combination with antiestrogens resulted in reduction of tumor size.
  • Molecular weight: 506.61
  • Formula: C27H32F2N8
  • CLOGP: 4.77
  • LIPINSKI: 1
  • HAC: 8
  • HDO: 1
  • TPSA: 75
  • ALOGS: -4.50
  • ROTB: 7

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Sept. 26, 2018 EMA Eli Lilly Nederland B.V.
Sept. 21, 2018 PMDA Eli Lilly Japan KK
Sept. 28, 2017 FDA ELI LILLY AND CO

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Diarrhoea 790.24 33.23 544 3999 559058 46122461
Therapy cessation 313.75 33.23 112 4431 26517 46655002
Malignant neoplasm progression 220.47 33.23 113 4430 64813 46616706
Disease progression 200.02 33.23 119 4424 91181 46590338
Therapy change 97.83 33.23 31 4512 5059 46676460
Dehydration 80.78 33.23 88 4455 159452 46522067
Death 80.53 33.23 128 4415 335420 46346099
Interstitial lung disease 77.38 33.23 54 4489 53895 46627624
Nausea 76.94 33.23 190 4353 687264 45994255
Therapy interrupted 65.06 33.23 28 4515 10763 46670756
White blood cell count decreased 62.19 33.23 65 4478 112166 46569353
Pneumonitis 56.71 33.23 35 4508 28385 46653134
Vomiting 48.03 33.23 123 4420 452671 46228848
Fatigue 46.72 33.23 147 4396 608550 46072969
Decreased appetite 46.35 33.23 74 4469 193762 46487757
Hospice care 42.98 33.23 17 4526 5278 46676241
Tumour marker increased 41.97 33.23 15 4528 3526 46677993
Metastases to liver 33.77 33.23 22 4521 19563 46661956

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event

Pharmacologic Action:

SourceCodeDescription
ATC L01EF03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Cyclin-dependent kinase (CDK) inhibitors
FDA MoA N0000175082 Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Hormone receptor positive malignant neoplasm of breast indication 417181009

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.14 Basic
pKa2 6.26 Basic
pKa3 5.0 Basic
pKa4 3.88 Basic
pKa5 2.67 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
100MG VERZENIO ELI LILLY AND CO N208716 Sept. 28, 2017 RX TABLET ORAL Feb. 26, 2021 IN COMBINULLTION WITH AN AROMATASE INHIBITOR AS INITIAL ENDOCRINE-BASED THERAPY FOR THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH HORMONE RECEPTOR-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
150MG VERZENIO ELI LILLY AND CO N208716 Sept. 28, 2017 RX TABLET ORAL Feb. 26, 2021 IN COMBINULLTION WITH AN AROMATASE INHIBITOR AS INITIAL ENDOCRINE-BASED THERAPY FOR THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH HORMONE RECEPTOR-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
200MG VERZENIO ELI LILLY AND CO N208716 Sept. 28, 2017 RX TABLET ORAL Feb. 26, 2021 IN COMBINULLTION WITH AN AROMATASE INHIBITOR AS INITIAL ENDOCRINE-BASED THERAPY FOR THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH HORMONE RECEPTOR-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
50MG VERZENIO ELI LILLY AND CO N208716 Sept. 28, 2017 RX TABLET ORAL Feb. 26, 2021 IN COMBINULLTION WITH AN AROMATASE INHIBITOR AS INITIAL ENDOCRINE-BASED THERAPY FOR THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH HORMONE RECEPTOR-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
100MG VERZENIO ELI LILLY AND CO N208716 Sept. 28, 2017 RX TABLET ORAL Sept. 28, 2022 NEW CHEMICAL ENTITY
150MG VERZENIO ELI LILLY AND CO N208716 Sept. 28, 2017 RX TABLET ORAL Sept. 28, 2022 NEW CHEMICAL ENTITY
200MG VERZENIO ELI LILLY AND CO N208716 Sept. 28, 2017 RX TABLET ORAL Sept. 28, 2022 NEW CHEMICAL ENTITY
50MG VERZENIO ELI LILLY AND CO N208716 Sept. 28, 2017 RX TABLET ORAL Sept. 28, 2022 NEW CHEMICAL ENTITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Cyclin-dependent kinase 4 Kinase INHIBITOR Ki 9.22 SCIENTIFIC LITERATURE DRUG LABEL
Cyclin-dependent kinase 6 Kinase INHIBITOR Ki 8.62 SCIENTIFIC LITERATURE DRUG LABEL

External reference:

IDSource
60UAB198HK UNII
4036932 VANDF
C3852841 UMLSCUI
6ZV PDB_CHEM_ID
CHEMBL3301610 ChEMBL_ID
46220502 PUBCHEM_CID
DB12001 DRUGBANK_ID
D10688 KEGG_DRUG
10036 INN_ID
C000590451 MESH_SUPPLEMENTAL_RECORD_UI
7382 IUPHAR_LIGAND_ID
1946825 RXNORM
262389 MMSL
33135 MMSL
d08665 MMSL
017349 NDDF
761851004 SNOMEDCT_US
763501007 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Verzenio HUMAN PRESCRIPTION DRUG LABEL 1 0002-4483 TABLET 50 mg ORAL NDA 33 sections
Verzenio HUMAN PRESCRIPTION DRUG LABEL 1 0002-4815 TABLET 100 mg ORAL NDA 33 sections
Verzenio HUMAN PRESCRIPTION DRUG LABEL 1 0002-5337 TABLET 150 mg ORAL NDA 33 sections
Verzenio HUMAN PRESCRIPTION DRUG LABEL 1 0002-6216 TABLET 200 mg ORAL NDA 33 sections