BMS-265246

ATP-competitive inhibitor of CDK1, CDK2

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(1 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Information

CDK1
CDK2

ATP-competitive inhibitor

More...

Probe Availability:

In Vitro Validations

Uniprot ID: P06493

Target Class: Kinase

Target SubClass: CMGC

Potency: IC 50

Potency Value: 6 nM

Potency Assay: In Vitro Kinase Inhibition

PDB ID for probe-target interaction (3D structure): --

Structure-activity relationship: The 2,6-difluorophenyl substitution was critical for potent inhibitory activity.

Target aliases:

Cyclin-dependent kinase 1, P34CDC2, CDKN1, CDC28A, ...

DOI Reference: 10.1158/1535-7163.MCT-10-0720

In Cell Validations

In Vivo Data

No in Vivo Validations

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Although BMS-265246 is shown (in Bioorg Med Chem Lett 2003, 13, 2405-2408) to be a potent inhibitor of CDK1 (IC50 6 nM) and CDK2 (9 nM) with selectivity over CDK4 (230 nM), no broader kinase selectivity data is reported. Although cyctotoxicity is reported in A2780 cells, there is no indication of whether or not this is on-target. In the absence of further data, BMS-265246 should be used with caution in the study of CDKs 1 and 2.

(last updated: 18 Jun 2016 )

SERP Ratings

In Cell Rating

SERP Comments:

This compound has limited aqueous solubility: water < 1mg/mL; ethanol < 1mg/mL; DMSO 20mg/mL. Selectivity for CDK1 and CDK2 over CDK4 was 38-fold and 25-fold, respectively. In the ovarian cancer cell line A2780, TI's were 126 (CDK1) and 84 (CDK2). Synthetic methodology is in place for the synthesis of larger quantities of BMS-265246. There are structural analogs with similar activity.

(last updated: 19 Jun 2016 )

SERP Ratings

In Cell Rating

(last updated: 15 Jun 2017 )