2f7x
Protein Kinase A bound to (S)-2-(1H-Indol-3-yl)-1-[5-((E)-2-pyridin-4-yl-vinyl)-pyridin-3-yloxymethyl]-ethylamine
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| , resolution 1.90Å | |||||||
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| Ligands: | |||||||
| Gene: | PRKACA (Bos taurus) | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Related: | 2F7E, 1YDS, 2F7Z
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
OverviewOverview
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.
About this StructureAbout this Structure
2F7X is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
ReferenceReference
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., Li Q, Li T, Zhu GD, Gong J, Claibone A, Dalton C, Luo Y, Johnson EF, Shi Y, Liu X, Klinghofer V, Bauch JL, Marsh KC, Bouska JJ, Arries S, De Jong R, Oltersdorf T, Stoll VS, Jakob CG, Rosenberg SH, Giranda VL, Bioorg Med Chem Lett. 2006 Mar 15;16(6):1679-85. Epub 2006 Jan 5. PMID:16403626
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