3IG7

Novel CDK-5 inhibitors - crystal structure of inhibitor EFP with CDK-2

Summary for 3IG7

• Entry DOI: 10.2210/pdb3ig7/pdb
• Related: 3IGG
• Descriptor: Cell division protein kinase 2, N-{1-[cis-3-(acetylamino)cyclobutyl]-1H-imidazol-4-yl}-2-(4-methoxyphenyl)acetamide (3 entities in total)
• Functional Keywords: protein kinase, transferase, serine/threonine protein kinase, atp-binding, cell cycle, cell division, mitosis, 4-aminoimidazole, kinase, nucleotide-binding, phosphoprotein, polymorphism, serine/threonine-protein kinase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 34344.92

Authors

Pandit, J. (deposition date: 2009-07-27, release date: 2009-09-08, Last modification date: 2024-10-16)

Primary citation

Helal, C.J.,Kang, Z.,Lucas, J.C.,Gant, T.,Ahlijanian, M.K.,Schachter, J.B.,Richter, K.E.,Cook, J.M.,Menniti, F.S.,Kelly, K.,Mente, S.,Pandit, J.,Hosea, N.
Potent and cellularly active 4-aminoimidazole inhibitors of cyclin-dependent kinase 5/p25 for the treatment of Alzheimer's disease.
Bioorg.Med.Chem.Lett., 19:5703-5707, 2009

PubMed Abstract: Utilizing structure-based drug design, a 4-aminoimidazole heterocyclic core was synthesized as a replacement for a 2-aminothiazole due to potential metabolically mediated toxicity. The synthetic route utilized allowed for ready synthesis of 1-substituted-4-aminoimidazoles. SAR exploration resulted in the identification of a novel cis-substituted cyclobutyl group that gave improved enzyme and cellular potency against cdk5/p25 with up to 30-fold selectivity over cdk2/cyclin E.

PubMed: 19700321
DOI: 10.1016/j.bmcl.2009.08.019

Experimental method

X-RAY DIFFRACTION (1.8 Å)