PMID: 25751268Mar 10, 2015Paper

Recent developments with metalloprotease inhibitor class of drug candidates for botulinum neurotoxins

Current Topics in Medicinal Chemistry
Gyanendra Kumar, Subramanyam Swaminathan

Abstract

Botulinum Neurotoxins are the most poisonous of all toxins with lethal dose in nanogram quantities. They are potential biological warfare and bioterrorism agents due to their high toxicity and ease of preparation. On the other hand BoNTs are also being increasingly used for therapeutic and cosmetic purposes, and with that the chances of accidental overdose are increasing. And despite the potential damage they could cause to human health, there are no post-intoxication drugs available so far. But progress is being made in this direction. The crystal structures in native form and bound with substrate peptides have been determined, and these are enabling structure-based drug discovery possible. High throughput assays have also been designed to speed up the screening progress. Substrate-based and small molecule inhibitors have been identified. But turning high affinity inhibitors into clinically viable drug candidates has remained a challenge. We discuss here the latest developments and the future challenges in drug discovery for Botulinum neurotoxins.

Citations

Jan 10, 2016·Toxicon : Official Journal of the International Society on Toxinology·Jiubiao GuoSheng Chen
Jul 30, 2016·Journal of Ethnopharmacology·Chinni YalamanchiliIkhlas A Khan
Aug 24, 2020·Bioorganic & Medicinal Chemistry·Jordan C ThompsonNicholas T Salzameda
Feb 20, 2021·ACS Medicinal Chemistry Letters·Martin AmezcuaNicholas T Salzameda
Aug 21, 2016·Bioorganic & Medicinal Chemistry·Yuchen ZhouRobert C Rizzo
May 12, 2021·Antimicrobial Agents and Chemotherapy·Arieh SchwartzRan Zichel

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