4ALU

Benzofuropyrimidinone Inhibitors of Pim-1

Summary for 4ALU

• Entry DOI: 10.2210/pdb4alu/pdb
• Related: 1XQZ 1XR1 1XWS 1YHS 1YI3 1YI4 1YWV 1YXS 1YXT 1YXU 1YXV 1YXX 2BIK 2BIL 2BZH 2BZI 2BZJ 2BZK 2C3I 2J2I 2XIX 2XIY 2XIZ 2XJ0 2XJ1 2XJ2 4A7C 4ALV 4ALW
• Descriptor: SERINE/THREONINE-PROTEIN KINASE PIM-1, IMIDAZOLE, 8-bromo-2-(2-chlorophenyl)[1]benzofuro[3,2-d]pyrimidin-4(3H)-one, ... (4 entities in total)
• Functional Keywords: proto-oncogene, transferase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Isoform 2: Cytoplasm. Isoform 1: Cell membrane: P11309
• Total number of polymer chains: 1
• Total formula weight: 37942.25

Authors

Stout, T.J.,Adams, L. (deposition date: 2012-03-05, release date: 2013-01-16, Last modification date: 2024-05-01)

Primary citation

Tsuhako, A.L.,Brown, D.S.,Koltun, E.S.,Aay, N.,Arcalas, A.,Chan, V.,Du, H.,Engst, S.,Franzini, M.,Galan, A.,Huang, P.,Johnston, S.,Kane, B.,Kim, M.H.,Laird, A.D.,Lin, R.,Mock, L.,Ngan, I.,Pack, M.,Stott, G.,Stout, T.J.,Yu, P.,Zaharia, C.,Zhang, W.,Zhou, P.,Nuss, J.M.,Kearney, P.C.,Xu, W.
The Design, Synthesis, and Biological Evaluation of Pim Kinase Inhibitors.
Bioorg.Med.Chem.Lett., 22:3732-, 2012

PubMed Abstract: A series of substituted benzofuropyrimidinones with pan-PIM activities and excellent selectivity against a panel of diverse kinases is described. Initial exploration identified aryl benzofuropyrimidinones that were potent, but had cell permeability limitation. Using X-ray crystal structures of the bound PIM-1 complexes with 3, 5m, and 6d, we were able to guide the SAR and identify the alkyl benzofuropyrimidinone (6l) with good PIM potencies, permeability, and oral exposure.

PubMed: 22542012
DOI: 10.1016/J.BMCL.2012.04.025

Experimental method

X-RAY DIFFRACTION (2.6 Å)