High throughput screening of a library based on kinase inhibitor scaffolds against Mycobacterium tuberculosis H37Rv - 02/02/12

Doi : 10.1016/j.tube.2011.05.005

Robert C. Reynolds ^a,^⁎ , Subramaniam Ananthan ^a,^{^{c
Tel.: +1 205 581 2822; fax: +1 205 581 2726.}} , Ellen Faaleolea ^b,^{^{d
Tel.: +1 301 228 2197; fax: +1 301 694 7223.}} , Judith V. Hobrath ^a,^{^{e
Tel.: +1 205 581 2761.}} , Cecil D. Kwong ^a,^{^{f
Tel.: +1 205 581 2746.}} , Clinton Maddox ^a,^{^{g
Tel.: +1 205 581 2802.}} , Lynn Rasmussen ^a,^{^{h
Tel.: +1 205 581 2259.}} , Melinda I. Sosa ^a,^{^{i
Tel.: +1 205 581 2440.}} , Elizabeth Thammasuvimol ^b,^{^{j
Tel.: +1 301 694 3232x240.}} , E. Lucile White ^a,^{^{k
Tel.: +1 205 581 2344.}} , Wei Zhang ^a,^{^{l
Tel.: +1 205 581 2361.}} , John A. Secrist ^a,^{^{m
Tel.: +1 205 581 2442.}}
^a Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA
^b Southern Research Institute, 431 Aviation Way, Frederick, MD 21701, USA

Corresponding author. Tel.: +1 205 581 2454; fax: +1 205 581 2447.

Summary

Kinase targets are being pursued in a variety of diseases beyond cancer, including immune and metabolic as well as viral, parasitic, fungal and bacterial. In particular, there is a relatively recent interest in kinase and ATP-binding targets in Mycobacterium tuberculosis in order to identify inhibitors and potential drugs for essential proteins that are not targeted by current drug regimens. Herein, we report the high throughput screening results for a targeted library of approximately 26,000 compounds that was designed based on current kinase inhibitor scaffolds and known kinase binding sites. The phenotypic data presented herein may form the basis for selecting scaffolds/compounds for further enzymatic screens against specific kinase or other ATP-binding targets in Mycobacterium tuberculosis based on the apparent activity against the whole bacteria in vitro.

Le texte complet de cet article est disponible en PDF.

Keywords : TAACF, Antitubercular, High throughput screening methods, Medicinal chemistry analysis, Designed kinase inhibitor library

Plan

Introduction

Kinases as drug targets

Design of the kinase screening library

The HTS screen

Discussion of active scaffolds

2-Acylaminothiopene-3-carboxamide and related compounds

Pyrazolo[1,5-a]pyrimidines

Tetrahydrobenzo[1,4]diazepin-2-ones

Substituted 1,2,3-benzotriazin-4(3H)-ones

Substituted benzopyran-2-ones

2-Aminobenzothiazoles

Substituted 2-benzylidenebenzofuran-3(2H)-ones

Substituted 2-(benzimidazol-2-yl)acrylonitriles

Export

Vol 92 - N° 1

P. 72-83 - janvier 2012 Retour au numéro

Article précédent

Distinct polyfunctional CD4⁺ T cell responses to BCG, ESAT-6 and CFP-10 in tuberculous pleurisy
Li Li, Dan Qiao, Qin Li, Xianlan Zhang, Suihua Lao, Changyou Wu

| Article suivant

Pyrazinoic acid efflux rate in Mycobacterium tuberculosis is a better proxy of pyrazinamide resistance
Mirko Zimic, Patricia Fuentes, Robert H. Gilman, Andrés H. Gutiérrez, Daniela Kirwan, Patricia Sheen

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

connectez-vous ou créez un compte

High throughput screening of a library based on kinase inhibitor scaffolds against Mycobacterium tuberculosis H37Rv - 02/02/12

Summary

Plan

Export citations

Fichier

Contenu

Accès rapides

Mon compte

Aide & support

Plateformes Elsevier Masson

Déclaration CNIL