2WIP: Structure Of Cdk2-Cyclin A Complexed With 8-Anilino-1- Methyl-4,5-Dihydro-1h-Pyrazolo[4,3-H] Quinazoline-3- Carboxylic Acid

The discovery of a novel class of inhibitors of cyclin dependent kinases (CDKs) is described. Starting from compound 1, showing good potency as inhibitor of CDKs but being poorly selective against a panel of serine-threonine and tyrosine kinases, new analogues were synthesized. Enhancement in selectivity, antiproliferative activity against A2780 human ovarian carcinoma cells, and optimization of the physical properties and pharmacokinetic profile led to the identification of highly potent and orally available compounds. Compound 28 (PHA-848125), which in the preclinical xenograft A2780 human ovarian carcinoma model showed good efficacy and was well tolerated upon repeated daily treatments, was identified as a drug candidate for further development. Compound 28 is currently undergoing phase I and phase II clinical trials.
PDB ID: 2WIPDownload
MMDB ID: 75551
PDB Deposition Date: 2009/5/14
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 2WIP: dimeric; determined by author and by software (PISA)
Molecular Components in 2WIP
Label Count Molecule
Proteins (2 molecules)
Cell Division Protein Kinase 2(Gene symbol: CDK2)
Molecule annotation
Cyclin-a2(Gene symbol: CCNA2)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB