✦ LIBER ✦

A Highly Potent and Selective Caspase 1 Inhibitor that Utilizes a Key 3-Cyanopropanoic Acid Moiety

✍ Scribed by Matthew B. Boxer; Amy M. Quinn; Min Shen; Ajit Jadhav; William Leister; Anton Simeonov; Douglas S. Auld; Craig J. Thomas

Publisher: John Wiley and Sons
Year: 2010
Tongue: English
Weight: 493 KB
Volume: 5
Category: Article
ISSN: 1860-7179
DOI: 10.1002/cmdc.200900531

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

Herein, we examine the potential of a nitrile‐containing propionic acid moiety as an electrophile for covalent attack by the active‐site cysteine residue of caspase 1. The syntheses of several cyanopropanate‐containing small molecules based on the optimized peptidic scaffold of prodrug VX‐765 were accomplished. These compounds were found to be potent inhibitors of caspase 1 (IC~50~ values ≤1 nM). Examination of these novel small molecules against a caspase panel demonstrated an impressive degree of selectivity for caspase 1 inhibition over other caspase isozymes. Assessment of hydrolytic stability and selected ADME properties highlighted these agents as potentially useful tools for studying caspase 1 down‐regulation in various settings, including in vivo analyses.

📜 SIMILAR VOLUMES

Inside Cover: A Highly Potent and Select

Inside Cover: A Highly Potent and Selective Caspase 1 Inhibitor that Utilizes a Key 3-Cyanopropanoic Acid Moiety (ChemMedChem 5/2010)

✍ Matthew B. Boxer; Amy M. Quinn; Min Shen; Ajit Jadhav; William Leister; Anton Si 📂 Article 📅 2010 🏛 John Wiley and Sons 🌐 English ⚖ 528 KB

The inside cover picture shows the caspase 1 inhibitor NCGC00183434 modeled in the active site making key contacts between the cysteine of the enzyme and the nitrile group of the inhibitor, as well as key contacts between the aspartic acid mimetic and core arginine residues. NCGC00183434 was found t

3-[6-(2-Dimethylamino-1-imidazol-1-yl-bu

3-[6-(2-Dimethylamino-1-imidazol-1-yl-butyl)-naphthalen-2-yloxy] -2,2-dimethyl-propionic Acid as a Highly Potent and Selective Retinoic Acid Metabolic Blocking Agent.

✍ Mark J. Mulvihill; et al. et al. 📂 Article 📅 2006 🏛 John Wiley and Sons ⚖ 24 KB

## Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

p38 MAP Kinase Inhibitors. Part 1. Desig

p38 MAP Kinase Inhibitors. Part 1. Design and Development of a New Class of Potent and Highly Selective Inhibitors Based on 3,4-Dihydropyrido[3,2-d]pyrimidone Scaffold.

✍ Swaminathan R. Natarajan; et al. et al. 📂 Article 📅 2003 🏛 John Wiley and Sons ⚖ 185 KB 👁 2 views

1-[3-Aminobenzisoxazol-5′-yl]-3-trifluor

1-[3-Aminobenzisoxazol-5′-yl]-3-trifluoromethyl-6- [2′-(3-(R)-hydroxy-N-pyrrolidinyl)methyl- [1,1′]-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-on# e (I) (BMS-740808) a Highly Potent, Selective, Efficacious, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa.

✍ Donald J. P. Pinto; et al. et al. 📂 Article 📅 2006 🏛 John Wiley and Sons ⚖ 10 KB 👁 1 views