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Comprehensive Medicinal Chemistry (CMC)

Coverage:
1900-present; updated annually
Derived from the Drug Compendium in Pergamon's Comprehensive Medicinal Chemistry, the CMC database provides 3D models and important biochemical properties (including drug class, logP, and pKa values) for over 7,000 pharmaceutical compounds. MDL updates CMC annually with compounds identified for the first time in USAN.
 
Focus:
Compounds used or studied as medicinal agents in humans; pharmacological agents; biologically active compounds; measured and estimated logP and pKA values

Size:
ca. 8000 molecules
ca. 7,100 models
updates add approximately 250 new molecules per year
An application:

Cinanserin is an inhibitor of the 3C-like proteinase of severe acute respiratory syndrome coronavirus and strongly reduces virus replication in vitro

Chen, L.a Show author details, Gui, C.a Show author details, Luo, X.a Show author details, Yang, Q.a Show author details, Günther, S.b Show author detailsEmail this author, Scandella, E.c Show author details, Drosten, C.b Show author details, Bai, D.a Show author details, He, X.a Show author details, Ludewig, B.c Show author details, Chen, J.a Show author details, Luo, H.a Show author details, Yang, Y.a Show author details, Yang, Y.a Show author details, Zou, J.a Show author details, Thiel, V.c Show author details, Chen, K.a Show author details, Shen, J.a Show author details, Shen, X.a Show author detailsEmail this author, Jiang, H.a d Show author details Correspondence address

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Department of Virology, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, 20359 Hamburg, Germany
Research Department, Kantonal Hospital St. Gallen, CH-9007 St. Gallen, Switzerland
School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China

Abstract

The 3C-like proteinase (3CLpro) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one of the most promising targets for anti-SARS-CoV drugs due to its crucial role in the viral life cycle. In this study, a database containing structural information of more than 8,000 existing drugs was virtually screened by a docking approach to identify potential binding molecules of SARS-CoV 3CLpro. As a target for screening, both a homology model and the crystallographic structure of the binding pocket of the enzyme were used. Cinanserin (SQ 10,643), a well-characterized serotonin antagonist that has undergone preliminary clinical testing in humans in the 1960s, showed a high score in the screening and was chosen for further experimental evaluation. Binding of both cinanserin and its hydrochloride to bacterially expressed 3CLpro of SARS-CoV and the related human coronavirus 229E (HCoV-229E) was demonstrated by surface plasmon resonance technology. The catalytic activity of both enzymes was inhibited with 50% inhibitory concentration (IC50) values of 5 μM, as tested with a fluorogenic substrate. The antiviral activity of cinanserin was further evaluated in tissue culture assays, namely, a replicon system based on HCoV-229E and quantitative test assays with infectious SARS-CoV and HCoV-229E. All assays revealed a strong inhibition of coronavirus replication at nontoxic drug concentrations. The level of virus RNA and infectious particles was reduced by up to 4 log units, with IC50 values ranging from 19 to 34 μM. These findings demonstrate that the old drug cinanserin is an inhibitor of SARS-CoV replication, acting most likely via inhibition of the 3CL proteinase. Copyright 2005, American Society for Microbiology. All Rights Reserved.

 

You can download here a sample ISIS/Base database with 100 structures. (CMC3DfindSample.DB (.zip))

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