2bpm

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spinqualitylabelsall models 2bpm, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

STRUCTURE OF CDK2-CYCLIN A WITH PHA-630529

Overview

Inhibitors of cyclin-dependent kinases (CDK) such as CDK2/cyclin A-E are, currently undergoing clinical trials to verify their potential as new, anticancer agents. In a previous article we described the lead discovery, process of a 3-aminopyrazole class of CDK2/cyclin A-E inhibitors. The, endpoint of this process was PNU-292137, a compound endowed with in vivo, antitumor activity in a mouse tumor xenograft model. We optimized this, lead compound to improve some physicochemical properties, notably, solubility and plasma protein binding. This lead optimization process, brought us to the discovery of, (2S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-[4-(2-oxo-1-pyrrolidinyl)phenyl]p, ropanamide (PHA-533533, 13), a compound with a balanced activity vs, druglike profile. Compound 13 inhibited ... [(full description)]

About this Structure

2BPM is a [Protein complex] structure of sequences from [Homo sapiens] with SO4 and 529 as [ligands]. Active as [Transferred entry: 2.7.11.1], with EC number [2.7.1.37]. Structure known Active Site: AC1. Full crystallographic information is available from [OCA].

Reference

3-Aminopyrazole inhibitors of CDK2/cyclin A as antitumor agents. 2. Lead optimization., Pevarello P, Brasca MG, Orsini P, Traquandi G, Longo A, Nesi M, Orzi F, Piutti C, Sansonna P, Varasi M, Cameron A, Vulpetti A, Roletto F, Alzani R, Ciomei M, Albanese C, Pastori W, Marsiglio A, Pesenti E, Fiorentini F, Bischoff JR, Mercurio C, J Med Chem. 2005 Apr 21;48(8):2944-56. PMID:15828833

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