5KBQ

Pak1 in complex with bis-anilino pyrimidine inhibitor

Summary for 5KBQ

• Entry DOI: 10.2210/pdb5kbq/pdb
• Descriptor: Serine/threonine-protein kinase PAK 1, [4-methyl-3-[methyl-[2-[(3-methylsulfonyl-5-morpholin-4-yl-phenyl)amino]pyrimidin-4-yl]amino]phenyl]methanol (3 entities in total)
• Functional Keywords: serine/threonine-protein kinase pak1, kinase, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : Q13153
• Total number of polymer chains: 2
• Total formula weight: 65148.28

Authors

Ferguson, A. (deposition date: 2016-06-03, release date: 2016-09-28, Last modification date: 2023-09-27)

Primary citation

McCoull, W.,Hennessy, E.J.,Blades, K.,Chuaqui, C.,Dowling, J.E.,Ferguson, A.D.,Goldberg, F.W.,Howe, N.,Jones, C.R.,Kemmitt, P.D.,Lamont, G.,Varnes, J.G.,Ward, R.A.,Yang, B.
Optimization of Highly Kinase Selective Bis-anilino Pyrimidine PAK1 Inhibitors.
ACS Med Chem Lett, 7:1118-1123, 2016

PubMed Abstract: Group I p21-activated kinase (PAK) inhibitors are indicated as important in cancer progression, but achieving high kinase selectivity has been challenging. A bis-anilino pyrimidine PAK1 inhibitor was identified and optimized through structure-based drug design to improve PAK1 potency and achieve high kinase selectivity, giving probe compound (). Reduction of lipophilicity to lower clearance afforded () as an probe compound with oral exposure in mouse. Such probes will allow further investigation of PAK1 biology.

PubMed: 27994749
DOI: 10.1021/acsmedchemlett.6b00322

Experimental method

X-RAY DIFFRACTION (2.58 Å)