General
Preferred name
ABEMACICLIB
Synonyms
LY-2835219 ()
LY2835219 ()
Abemaciclib methanesulfonate ()
LY2835219 (methanesulfonate) ()
abemaciclib mesylate ()
LY2835219 mesylate ()
CDK4/6 dual inhibitor ()
LY2835219 (methanesulfonate)abemaciclib mesylate ()
LY2835219 methanesulfonate ()
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]- ()
Abemaciclib (methanesulfonate) ()
VERZENIO ()
VERZENIOS ()
LY2835219 free base ()
Abemaciclib mesylate (LY2835219) ()
abemaciclib (LY2835219) ()
LY2835219 ()
P&D ID
PD038907
CAS
1231929-97-7
1231930-82-7
Tags
available
drug
probe
Approved by
FDA
EMA
PMDA
First approval
2017
Drug indication
Solid tumour/cancer
Breast cancer
Drug Status
approved
investigational
Max Phase
4.0
Probe info
Probe type
experimental probe
Probe sources
Probe targets
[[ compound.targets[t].gene_name ]]
Probe control
Probe control not defined
Orthogonal probes
5
No orthogonal probes found
Similar probes
5
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION
LY2835219 is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6 .
PHARMACODYNAMICS
In combination with fulvestrant, the progression-free survival for patients with HR-positive, HER2-negative breast cancer was 16.4 months compared to 9.3 months for patients taking a placebo with fulvestrant. As a monotherapy, 19.7% of patients taking abemaciclib achieved complete or partial shrinkage of their tumors for a median 8.6 months after treatment [L1003]. Abemaciclib induces cell cycle arrest and exerts an antitumor activity in human tumor xenograft models [A27281]. ; ; In patient investigations and a healthy volunteer study, abemaciclib is not shown to induce any clinically significant changes in the QTc interval [FDA Label].
MOA
Regulation of cell cycle is crucial in maintaining proper cell growth; dysregulated cell cycle signalling pathway is a key component in inducing hyperproliferation of cells and tumor formation in various cancers. G1 to S phase cell cycle progression, or transition through the G1 restriction point (R), is promoted by the retinoblastoma tumor suppressor protein (Rb)-mediated pathway. Activation of Rb-mediated pathway requires the interaction of Cyclin-dependent kinases (CDK) 4 and 6 with D-type cyclins, which drives the formation of active CDK4/CDK6 and subsequent phosphorylation of Rb [A27281, A27282]. ; ; Rb is a tumor suppressant protein that inhibits proliferation through binding to and suppressing the activity of the E2F family of transcription factors [A27281]. However, phosphorylation of Rb relieves suppression of E2F to allow expression of genes required for passage through the restriction point [A27281]. This leads to increased expression of downstream signalling molecules and activity of protein kinases that promote the cell cycle progression and initiation of DNA replication. Phosphorylation of Rb and other proteins by CDK4/6 additionally leads to transcription of genes involved in cell cycle-independent activities including signal transduction, DNA repair transcriptional control, and mRNA processing [A27281]. ; ; Abemaciclib selectively inhibits CDK4 and CDK6 with low nanomolar potency, inhibits Rb phosphorylation resulting in a G1 arrest and inhibition of proliferation, and its activity is specific for Rb-proficient cells [A27281]. Unlike other CDK inhibitors such as [DB09073] and [DB11730], abemaciclib exhibits greater selectivity for CDK4 compared to CDK6 [A27282].
INDICATION
* Indicated 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. ; ; * Inidicated 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.
DESCRIPTION
Abemaciclib (LY2835219) is a selective ATP-competitive inhibitor of the cyclin-dependent kinases CDK4 and CDK6 .
(GtoPdb)
MOA
Inhibitor
(Chemical Probes.org)
DESCRIPTION
On September 28, 2017, the Food and Drug Administration approved abemaciclib (VERZENIO, Eli Lilly and Company) in combination with fulvestrant for women with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. In addition, abemaciclib was approved as monotherapy for women and men with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.
(PKIDB)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
45
Organisms
1
Compound Sets
28
CDK inhibitor database (CDKiDB)
ChEMBL Approved Drugs
ChEMBL Drugs
Chemical Probes.org
Clinical kinase drugs
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
EUbOPEN Chemogenomics Library
Guide to Pharmacology
High-quality chemical probes
LINCS compound set
LSP-MoA library (Laboratory of Systems Pharmacology)
LSP-OptimalKinase library (Laboratory of Systems Pharmacology)
NCATS Inxight Approved Drugs
NIH Approved Oncology Drugs
PKIDB
ReFrame library
Selleckchem Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
45
Molecular Weight
506.27
Hydrogen Bond Acceptors
8
Hydrogen Bond Donors
1
Rotatable Bonds
7
Ring Count
5
Aromatic Ring Count
4
cLogP
4.94
TPSA
75.0
Fraction CSP3
0.41
Chiral centers
0.0
Largest ring
6.0
QED
0.38
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Targets
CDK4,CDK6
Pathway
Cell Cycle/Checkpoint
Cell Cycle/DNA Damage
Target
CDK4
CDK6
CDK4, CDK6
CDK
Indication
breast cancer
MOA
CDK inhibitor
Target class
Kinase, Kinase
Target subclass
CMGC, CMGC
Recommended Cell Concentration
None
Source data
