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.
Keywords: Bioterrorism, Clostridium botulinum, Drug discovery, Neurotoxin, Protease inhibitor.
Current Topics in Medicinal Chemistry
Title:Recent Developments with Metalloprotease Inhibitor Class of Drug Candidates for Botulinum Neurotoxins
Volume: 15 Issue: 7
Author(s): Gyanendra Kumar and Subramanyam Swaminathan
Affiliation:
Keywords: Bioterrorism, Clostridium botulinum, Drug discovery, Neurotoxin, Protease inhibitor.
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.
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Cite this article as:
Kumar Gyanendra and Swaminathan Subramanyam, Recent Developments with Metalloprotease Inhibitor Class of Drug Candidates for Botulinum Neurotoxins, Current Topics in Medicinal Chemistry 2015; 15 (7) . https://dx.doi.org/10.2174/1568026615666150309150338
DOI https://dx.doi.org/10.2174/1568026615666150309150338 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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