3VSX

Human renin in complex with compound 18

Summary for 3VSX

• Entry DOI: 10.2210/pdb3vsx/pdb
• Related: 3VSW
• Descriptor: Renin, 2-acetamido-2-deoxy-beta-D-glucopyranose, (2S,4S,5S)-5-amino-N-(3-amino-2,2-dimethyl-3-oxopropyl)-6-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-2-(propan-2-yl)hexanamide (3 entities in total)
• Functional Keywords: ras, hypertension, inhibitor, aspartyl protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P00797
• Total number of polymer chains: 2
• Total formula weight: 76024.62

Authors

Takahashi, M.,Hanzawa, H. (deposition date: 2012-05-11, release date: 2012-07-25, Last modification date: 2024-11-20)

Primary citation

Nakamura, Y.,Sugita, C.,Meguro, M.,Miyazaki, S.,Tamaki, K.,Takahashi, M.,Nagai, Y.,Nagayama, T.,Kato, M.,Suemune, H.,Nishi, T.
Design and optimization of novel (2S,4S,5S)-5-amino-6-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)-4-hydroxy-2-isopropylhexanamides as renin inhibitors
Bioorg.Med.Chem.Lett., 22:4561-4566, 2012

PubMed Abstract: Introduction of the 2,2-dimethyl-4-phenylpiperazin-5-one scaffold into the P(3)-P(1) portion of the (2S,4S,5S)-5-amino-6-dialkylamino-4-hydroxy-2-isopropylhexanamide backbone dramatically increased the renin inhibitory activity without using the interaction to the S(3)(sp) pocket. Compound 31 exhibited >10,000-fold selectivity over other human proteases, and 18.5% oral bioavailability in monkey.

PubMed: 22726934
DOI: 10.1016/j.bmcl.2012.05.092

Experimental method

X-RAY DIFFRACTION (2.8 Å)