Delving into the Latest Updates on SEQ-9 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

23S rRNA

Mechanism

23S rRNA inhibitors(23S Ribosomal RNA inhibitors), Mycobacterium tuberculosis inhibitors

Therapeutic Areas

Infectious Diseases

Active Indication

Tuberculosis

Inactive Indication-

Originator Organization

Sanofi

Active Organization

Sanofi

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC60H100N4O20S

InChIKeyJCUPFQUUARRICQ-DXXMFXFBSA-N

CAS Registry-

Author: Tyagi, Sandeep ; Kaneko, Takushi ; Upton, Anna ; Cui, Zhicheng ; Benedetti, Yannick ; Bordon-Pallier, Florence ; Sacchettini, James C ; Yusupova, Gulnara ; Xing, Zhongliang ; Barrio, María Belén ; Zhang, Jidong ; Betoudji, Fabrice ; Rak, Alexey ; Cantalloube, Cathy ; Roubert, Christine ; Blanc, Isabelle ; Sans, Stephanie ; Li, Xiaojun ; Lair, Christine ; Franzblau, Scott G ; Nuermberger, Eric ; Baurin, Nicolas ; Yusupov, Marat ; Lagrange, Sophie ; Yang, T J ; Fraisse, Laurent ; Zhang, Junjie ; Silve, Sandra ; Jenner, Lasse B ; Fotouhi, Nader ; Amaning, Kwame

The emergence of drug-resistant tuberculosis has created an urgent need for new anti-tubercular agents. Here, we report the discovery of a series of macrolides called sequanamycins with outstanding in vitro and in vivo activity against Mycobacterium tuberculosis (Mtb). Sequanamycins are bacterial ribosome inhibitors that interact with the ribosome in a similar manner to classic macrolides like erythromycin and clarithromycin, but with binding characteristics that allow them to overcome the inherent macrolide resistance of Mtb. Structures of the ribosome with bound inhibitors were used to optimize sequanamycin to produce the advanced lead compound SEQ-9. SEQ-9 was efficacious in mouse models of acute and chronic TB as a single agent, and it demonstrated bactericidal activity in a murine TB infection model in combination with other TB drugs. These results support further investigation of this series as TB clinical candidates, with the potential for use in new regimens against drug-susceptible and drug-resistant TB.

100 Deals associated with SEQ-9

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