Development of Dimethylisoxazole-Attached Imidazo[1,2-]pyridines as Potent and Selective CBP/P300 Inhibitors.

The use of epigenetic bromodomain inhibitors as anticancer therapeutics has transitioned from targeting bromodomain extraterminal domain (BET) proteins into targeting non-BET bromodomains. The two most relevant non-BET bromodomain oncology targets are cyclic AMP response element-binding protein (CBP) and E1A binding protein P300 (EP300). To explore the growing CBP/EP300 interest, we developed a highly efficient two-step synthetic route for dimethylisoxazole-attached imidazo[1,2-]pyridine scaffold-containing inhibitors.

Synergistic efficacy of alkyltrimethylammonium bromide, chlorhexidine digluconate on diverse bacterial strains causing red-heat and purple-stain deteriorations of leather.

This investigation assessed the synergistic effectiveness of alkyltrimethylammonium bromide (ATMB) and chlorhexidine digluconate (CDG) on selected microbes causing red-heat and purple stain degradations on salt-cured hides and leather products. This biological phenomenon ultimately deteriorates the finished leather quality and grounds considerable economic losses for leather industry. In tryptic soy broth, combination of ATMB and/CDG at the concentration of 900/90 ppm for predefined time interval of 1, 3, and 6 min caused in 0.

Inhibition of Polo-like kinase 1 (PLK1) facilitates the elimination of HIV-1 viral reservoirs in CD4 T cells ex vivo.

Although combination antiretroviral therapy is effective in controlling HIV-1 infection, latent HIV-1 proviruses cannot be eliminated. HIV-1 reactivation induced by the mere use of latency-reversing agents is insufficient to render death of reservoir cells, indicating that certain intrinsic survival mechanisms exist. We report that Polo-like kinase 1 (PLK1) plays a critical role in survival of CD4 T cells that undergo HIV-1 reactivation from latency or de novo infection.

Small-Molecule Dual PLK1 and BRD4 Inhibitors are Active Against Preclinical Models of Pediatric Solid Tumors.

Simultaneous inhibition of multiple molecular targets is an established strategy to improve the continuance of clinical response to therapy. Here, we screened 49 molecules with dual nanomolar inhibitory activity against BRD4 and PLK1, best classified as dual kinase-bromodomain inhibitors, in pediatric tumor cell lines for their antitumor activity. We identified two candidate dual kinase-bromodomain inhibitors with strong and tumor-specific activity against neuroblastoma, medulloblastoma, and rhabdomyosarcoma tumor cells.

Efficacy of alkyltrimethylammonium bromide for decontaminating salt-cured hides from the red heat causing moderately halophilic bacteria.

Conventionally, animal hide and skin necessitates 95% saturated brine solution (SBS) for its preservation. This salt is primarily derived from different sources including solar-saltern, evaporation ponds, etc., which are laden with different types of halophilic micro-organisms.