May 12th<\/p>\n
https:\/\/pubs.acs.org\/doi\/abs\/10.1021\/acs.jmedchem.5c00112<\/a><\/p>\n Abstract<\/p>\n In an era of escalating antibiotic resistance, there is a pressing need for innovative strategies to develop novel antibiotics. Gram-negative bacteria, characterized by their robust dual-membrane, are intrinsically resistant to a wide range of antibiotics and can readily develop new resistances. Members of this bacterial class comprise numerous pathogenic organisms, including the primary cause of gastric cancer,\u00a0Helicobacter pylori<\/i>. In this study, we used the Giga-sized collection of theoretical molecules inside Enamine\u2019s REAL Space to identify inhibitors for\u00a0H. pylori<\/i>\u00a0glutamate racemase. These compounds displayed a diverse range of activity in preventing\u00a0H. pylori<\/i>\u00a0growth, with our most potent hits capable of selective full growth inhibition for metronidazole and clarithromycin resistant\u00a0H. pylori<\/i>\u00a0strains. Alongside the introduction of a novel antibiotic class for this carcinogenic pathogen, our unique implementation of REAL Space holds great promise for Gram-negative antibiotic development as a whole.<\/p>\n May 9th<\/p>\n https:\/\/pubs.acs.org\/doi\/abs\/10.1021\/acs.jmedchem.4c02293<\/a><\/p>\n Abstract<\/p>\n Activin receptor-like kinase 5 (ALK5) is a type I receptor serine\/threonine kinase and responsible for the TGF-\u03b2 signaling pathway. ALK5 is thought to be a key player in the tumor microenvironment to promote tumor progression by affecting the anticancer immunity. Therefore, ALK5 is an attractive drug target for modulating TGF-\u03b2 signaling pathways to improve the therapeutic efficacy of cancer immunotherapy. We report the optimization of a series of thiazole analogues starting from lead compound\u00a06<\/b>, focusing on improving off-target selectivity. Compound\u00a019f<\/b>\u00a0(HM-279) was identified as a potent ALK5 inhibitor with an acceptable off-target selectivity and favorable ADME\/PK properties. Oral administration of HM-279 demonstrated antitumor activity in a CT26.WT colon carcinoma syngeneic mouse model as a single agent and in combination with the anti-PD-1 antibody through CD8+<\/sup>\u00a0T cell immunity.<\/p>\n May 6th<\/p>\nDiscovery of HM-279, a Potent Inhibitor of ALK5 for Improving Therapeutic Efficacy of Cancer Immunotherapy<\/span><\/h2>\n
DNA-Encoded Library Screen Identifies Novel Series of Respiratory Syncytial Virus Polymerase Inhibitors<\/span><\/h2>\n