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Recently, there has been social controversy regarding whether benzimidazole anthelmintic drugs can be used as anticancer drugs. On this note, we wish to address the use of current benzimidazole anthelmintic drugs for the treatment of cancer patients. We explored the anticancer efficacy of benzimidazole anthelmintic drugs in vitro and their mechanism of action. We also conducted pharmacokinetic studies of two benzimidazole anthelmintics and assessed the predictive systemic efficacy. Finally, we present the anticancer efficacy of benzimidazole anthelmintics' putative metabolites from hydrolysis. Our data suggest that benzimidazole anthelmintic drugs are not expected to show systemic anticancer efficacy in vivo due to poor pharmacokinetic parameters. Therefore, patients should not consider oxibendazole or fenbendazole as cancer treatment option. [ABSTRACT FROM AUTHOR]

Bromodomain and extra-terminal (BET) proteins, a class of epigenetic reader domains has emerged as a promising new target class for small molecule drug discovery for the treatment of cancer, inflammatory, and autoimmune diseases. Starting from in silico screening campaign, herein we report the discovery of novel BET inhibitors based on [1,2,4]triazolo[4,3- a ]quinoxaline scaffold and their biological evaluation. The hit compound was optimized using the medicinal chemistry approach to the lead compound with excellent inhibitory activities against BRD4 in the binding assay. The substantial antiproliferative activities in human cancer cell lines, promising drug-like properties, and the selectivity for the BET family make the lead compound ( 13 ) as a novel BRD4 inhibitor motif for anti-cancer drug discovery. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis of bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines is described and their structure–activity-relationship to anaplastic lymphoma kinase (ALK) is presented. KRCA-0008 is selective and potent to ALK and Ack1, and displays drug-like properties without hERG liability. KRCA-0008 demonstrates in vivo efficacy comparable to Crizotinib in xenograft mice model. [Copyright &y& Elsevier]