2F7X

Protein Kinase A bound to (S)-2-(1H-Indol-3-yl)-1-[5-((E)-2-pyridin-4-yl-vinyl)-pyridin-3-yloxymethyl]-ethylamine

Summary for 2F7X

• Entry DOI: 10.2210/pdb2f7x/pdb
• Related: 1YDS 2F7E 2F7Z
• Descriptor: cAMP-dependent protein kinase, alpha-catalytic subunit, PKI, inhibitory peptide, (1S)-2-(1H-INDOL-3-YL)-1-[({5-[(E)-2-PYRIDIN-4-YLVINYL]PYRIDIN-3-YL}OXY)METHYL]ETHYLAMINE, ... (4 entities in total)
• Functional Keywords: protein kinase a, akt inhibitors, transferase
• Biological source: Bos taurus (cattle)
• Cellular location: Cytoplasm: P00517
• Total number of polymer chains: 2
• Total formula weight: 43274.51

Authors

Li, Q.,Li, T.,Zhu, G.D.,Gong, J.,Claibone, A.,Dalton, C.,Luo, Y.,Johnson, E.F.,Shi, Y.,Liu, X.,Klinghofer, V.,Bauch, J.L.,Marsh, K.C.,Bouska, J.J.,Arries, S.,De Jong, R.,Oltersdorf, T.,Stoll, V.S.,Jakob, C.G.,Rosenberg, S.H.,Giranda, V.L. (deposition date: 2005-12-01, release date: 2006-06-27, Last modification date: 2024-02-14)

Primary citation

Li, Q.,Li, T.,Zhu, G.D.,Gong, J.,Claibone, A.,Dalton, C.,Luo, Y.,Johnson, E.F.,Shi, Y.,Liu, X.,Klinghofer, V.,Bauch, J.L.,Marsh, K.C.,Bouska, J.J.,Arries, S.,De Jong, R.,Oltersdorf, T.,Stoll, V.S.,Jakob, C.G.,Rosenberg, S.H.,Giranda, V.L.
Discovery of trans-3,4'-bispyridinylethylenes as potent and novel inhibitors of protein kinase B (PKB/Akt) for the treatment of cancer: Synthesis and biological evaluation.
Bioorg.Med.Chem.Lett., 16:1679-1685, 2006

PubMed Abstract: A novel series of Akt/PKB inhibitors derived from a screening lead (1) has been prepared. The novel trans-3,4'-bispyridinylethylenes described herein are potent inhibitors of Akt/PKB with IC(50) values in the low double-digit nanomolar range against Akt1. Compound 2q shows excellent selectivity against distinct families of kinases such as tyrosine kinases and CAMK, and displays poor to modest selectivity against closely related kinases in the AGC and CMGC families. The cellular activities including inhibition of cell growth and phosphorylation of downstream target GSK3 are also described. The X-ray structure of compound 2q complexed with PKA in the ATP binding site was determined.

PubMed: 16403626
DOI: 10.1016/j.bmcl.2005.12.017

Experimental method

X-RAY DIFFRACTION (1.9 Å)