Delving into the Latest Updates on CRS-0393 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target-

Mechanism

Cell wall inhibitors, Membrane proteins inhibitors

Therapeutic Areas

Infectious Diseases

Active Indication

Mycobacterium Infections, Nontuberculous

Inactive Indication-

Originator Organization

Crestone Holdings Ltd.

Active Organization

Crestone Holdings Ltd.

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Sun, Xicheng ; Hoang, Teresa ; Rimal, Binayak ; Ribble, Wendy ; De Groote, Mary A ; Mason, Clifford ; Lamichhane, Gyanu ; Youmans, Tessa ; Gonzalez-Juarrero, Mercedes ; Walz, Amanda ; Stevens, Casey M ; Zgurskaya, Helen I ; Jarvis, Thale C ; Jackson, Mary ; Ordway, Diane ; Li, Wei ; Pearce, Camron ; Ochsner, Urs A ; Liu, Hang ; Day, Joshua ; Panthi, Chandra M

The benzothiazole amide CRS0393 demonstrated excellent in vitro activity against nontuberculous mycobacteria (NTM), including M. abscessus isolates from cystic fibrosis (CF) patients, with minimum inhibitory concentrations (MICs) of ≤0.03-0.5 μg/mL. The essential transport protein MmpL3 was confirmed as the target via analysis of spontaneous resistant mutants and further biological profiling. In mouse pharmacokinetic studies, intratracheal instillation of a single dose of CRS0393 resulted in high concentrations of drug in epithelial lining fluid (ELF) and lung tissue, which remained above the M. abscessus MIC for at least 9 hours post-dose. This exposure resulted in a penetration ratio of 261 for ELF and 54 for lung tissue relative to plasma. CRS0393 showed good oral bioavailability, particularly when formulated in kolliphor oil, with a lung-to-plasma penetration ratio ranging from 0.5 to 4. CRS0393 demonstrated concentration-dependent reduction of intracellular M. abscessus in a THP-1 macrophage infection model. CRS0393 was well tolerated following intranasal administration (8 mg/kg) or oral dosing (25 mg/kg) once daily for 28 days in dexamethasone-treated C3HeB/FeJ mice. Efficacy against M. abscessus strain 103 was achieved via the intranasal route, while oral dosing will need further optimization. CRS0393 holds promise for development as a novel agent with broad antimycobacterial activity.

100 Deals associated with CRS-0393

Login to view more data