2GU8

Discovery of 2-Pyrimidyl-5-Amidothiophenes as Novel and Potent Inhibitors for AKT: Synthesis and SAR Studies

Summary for 2GU8

• Entry DOI: 10.2210/pdb2gu8/pdb
• Descriptor: CAMP-dependent protein kinase, alpha-catalytic subunit, inhibitor of CAMP-dependent protein kinase, N-[(1S)-2-AMINO-1-(2,4-DICHLOROBENZYL)ETHYL]-5-[2-(METHYLAMINO)PYRIMIDIN-4-YL]THIOPHENE-2-CARBOXAMIDE, ... (4 entities in total)
• Functional Keywords: camp-dependent protein kinase, pka, akt, kinase, drug design, ternary complex, signaling protein, transferase-inhibitor complex, transferase/inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (By similarity): P17612
• Total number of polymer chains: 2
• Total formula weight: 42076.76

Authors

Murray, J.M. (deposition date: 2006-04-28, release date: 2007-05-01, Last modification date: 2024-10-16)

Primary citation

Lin, X.,Murray, J.M.,Rico, A.C.,Wang, M.X.,Chu, D.T.,Zhou, Y.,Del Rosario, M.,Kaufman, S.,Ma, S.,Fang, E.,Crawford, K.,Jefferson, A.B.
Discovery of 2-pyrimidyl-5-amidothiophenes as potent inhibitors for AKT: synthesis and SAR studies
Bioorg.Med.Chem.Lett., 16:4163-4168, 2006

PubMed Abstract: A series of 2-pyrimidyl-5-amidothiophenes has been synthesized and evaluated for AKT inhibition. SAR studies resulted in potent inhibitors of AKT with IC(50) values as low as single digit nanomolar as represented by compound 2aa. Compound 2aa showed cellular activity including antiproliferation and downstream target modulation. Selectivity profile is described. A co-crystal of 2aa with PKA is determined and discussed.

PubMed: 16765046
DOI: 10.1016/j.bmcl.2006.05.092

Experimental method

X-RAY DIFFRACTION (2.2 Å)