Benzimidazoles and Pharmaceutical Compositions Thereof
A novel cell division inhibitor with efficacy against Mycobacterium tuberculosis Background: Multidrug-resistant tuberculosis (MDR-TB) and extensively drug resistant TB (XDR-TB) are a significant public health threat for TB control efforts. Despite efforts in last 50 years, development of new TB treatments have been limited to drug targets like cell wall biosynthesis, ATP synthesis, RNA synthesis, leading to resistance in these areas. Hence, there is a need to discover novel drugs that target other bacterial processes in order to counter the developed bacterial resistance. Technology Overview: Researchers at Stony Brook University have focused their drug discovery program on the bacterial septum formation and cell division protein, FtsZ. The researchers have developed novel 3rd generation trisubstituted benzimidazoles directed against FtsZ of _M. tuberculosis_ H37Rv and the lead compound, SB-P17G-A38, shows efficacy equivalent to Isonaizid in an acute mouse model of _M. tuberculosis_ (![Figure 1](https://s3-eu-west-1.amazonaws.com/assets.in-part.com/figures/toiD9nUToqOpxTh8UWCG_TBFig1.png)). Additionally, the 3rd generation benzimidazoles improved human and mouse plasma and metabolic stability when compared to the previous lead. Together, these studies demonstrate that SB-P17G-A38 has potency against _M. tuberculosis_ clinical strains, and that trisubstituted benzimidazoles continue to be a platform for the development of novel inhibitors with efficacy. Stage of Development: - Animal data - Metabolic stability and plasma stability data - Time kill curve Further Details: Knudson et al. J. Antimicrob Chemother.2015 Nov: 70(11); 3070-3 Advantages: -Novel mechanism of action
-Improved plasma and metabolic stability
-Can be used in combination therapy
-Bactericidal Applications: - Antibacterial, including Tuberculosis R-7938 Intellectual Property Summary: Patented Stage of Development: Issued patents: US (8,232,410), EU, Japan, South Africa, Mexico, Canada. Licensing Potential: Licensing Status: null Additional Information: antibacterial,tuberculosis,bacterial,bacterial infection,public health,drug targets,cell walls,drug discovery,lead compound,metabolic,novel inhibitor,inhibitors,combination therapy,multidrug-resistant,novel drug target,drug target,bactericidal,mycobacterium tuberculosis https://stonybrook.technologypublisher.com/files/sites/sgwhn7btp20xhwyqfqfa_tuberculosis.png Please note, header image is purely illustrative. Source: NIAID, PHIL, CDC, public domain.