4APP

Crystal Structure of the Human p21-Activated Kinase 4 in Complex with (S)-N-(5-(3-benzyl-1-methylpiperazine-4-carbonyl)-6,6-dimethyl-1,4,5, 6-tetrahydropyrrolo(3,4-c)pyrazol-3-yl)-3-phenoxybenzamide

Summary for 4APP

• Entry DOI: 10.2210/pdb4app/pdb
• Related: 2BVA 2CDZ 2J0I 2X4Z
• Descriptor: SERINE/THREONINE-PROTEIN KINASE PAK 4, N-[6,6-dimethyl-5-[(2S)-4-methyl-2-(phenylmethyl)piperazin-1-yl]carbonyl-2,4-dihydropyrrolo[3,4-c]pyrazol-3-yl]-3-phenoxy-benzamide, GLYCEROL, ... (4 entities in total)
• Functional Keywords: transferase, protein kinase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 34081.61

Authors

Knighton, D.D.,Deng, Y.L.,Wang, C.,Guo, C.,McAlpine, I.,Zhang, J.,Kephart, S.,Johnson, M.C.,Li, H.,Bouzida, D.,Yang, A.,Dong, L.,Marakovits, J.,Tikhe, J.,Richardson, P.,Guo, L.C.,Kania, R.,Edwards, M.P.,Kraynov, E.,Christensen, J.,Piraino, J.,Lee, J.,Dagostino, E.,Del-Carmen, C.,Smeal, T.,Murray, B.W. (deposition date: 2012-04-04, release date: 2012-06-06, Last modification date: 2024-10-23)

Primary citation

Guo, C.,Mcalpine, I.,Zhang, J.,Knighton, D.D.,Kephart, S.,Johnson, M.C.,Li, H.,Bouzida, D.,Yang, A.,Dong, L.,Marakovits, J.,Tikhe, J.,Richardson, P.,Guo, L.C.,Kania, R.,Edwards, M.P.,Kraynov, E.,Christensen, J.,Piraino, J.,Lee, J.,Dagostino, E.,Del-Carmen, C.,Deng, Y.L.,Smeal, T.,Murray, B.W.
Discovery of Pyrroloaminopyrazoles as Novel Pak Inhibitors.
J.Med.Chem., 55:4728-, 2012

PubMed Abstract: The P21-activated kinases (PAK) are emerging antitumor therapeutic targets. In this paper, we describe the discovery of potent PAK inhibitors guided by structure-based drug design. In addition, the efflux of the pyrrolopyrazole series was effectively reduced by applying multiple medicinal chemistry strategies, leading to a series of PAK inhibitors that are orally active in inhibiting tumor growth in vivo.

PubMed: 22554206
DOI: 10.1021/JM300204J

Experimental method

X-RAY DIFFRACTION (2.2 Å)