3OOT

Crystal Structure Analysis of Renin-indole-piperazin inhibitor complexes

Summary for 3OOT

• Entry DOI: 10.2210/pdb3oot/pdb
• Related: 3OQF 3OQK
• Descriptor: Renin, 2-acetamido-2-deoxy-beta-D-glucopyranose, 2-(3-fluoro-2-methylbenzyl)-4-methyl-1-phenyl-3-(piperazin-1-ylcarbonyl)-1H-indol-5-ol, ... (4 entities in total)
• Functional Keywords: renin human, aspartyl protease, renin inhibition, hypertension, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P00797
• Total number of polymer chains: 2
• Total formula weight: 75891.51

Authors

Bocskei, Z. (deposition date: 2010-08-31, release date: 2010-10-27, Last modification date: 2024-10-16)

Primary citation

Scheiper, B.,Matter, H.,Steinhagen, H.,Stilz, U.,Bocskei, Z.,Fleury, V.,McCort, G.
Discovery and optimization of a new class of potent and non-chiral indole-3-carboxamide-based renin inhibitors.
Bioorg.Med.Chem.Lett., 20:6268-6272, 2010

PubMed Abstract: Selective inhibition of the aspartyl protease renin has gained attraction as an interesting approach to control hypertension and associated cardiovascular risk factors given its unique position in the renin-angiotensin system. Using a combination of high-throughput screening, parallel synthesis, X-ray crystallography and structure-based design, we identified and optimized a novel series of potent and non-chiral indole-3-carboxamides with remarkable potency for renin. The most potent compound 5k displays an IC(50) value of 2nM.

PubMed: 20850300
DOI: 10.1016/j.bmcl.2010.08.092

Experimental method

X-RAY DIFFRACTION (2.55 Å)