Antitumor activity of DPS-2 was further validated in vivo, as DPS-2 treatment of mouse xenografts of Colo-205 colorectal cancer cells remarkably reduced their tumor formation properties. After testing activities of several signaling pathways, the compound was found to have a dual inhibition of two major proliferative/survival pathways, MEK/ERK and PI3K/AKT, in both CRC and melanoma, thus providing a mechanistic evidence for its potent anticancer activity. More detailed analysis has shown that DPS-2 can kill cancer cells by apoptosis, reducing at the same time their autophagy properties. Treatments by 2-5 μM DPS-2 of several CRC and melanoma cell lines bearing either BRAF or KRAS mutations have shown a remarkable effect on cell viability in 2D and 3D cultures. A new compound based on the benzothiophene nucleus was synthesized, based on previous important outcomes on other pharmaceutical preparations, to be tested as potential anticancer agent. In addition, single or multitarget kinase inhibitors against MEK/ERK and PI3K/AKT pathways are of potential therapeutic advantage. Development of novel bioactive compounds against KRAS and/or BRAF mutant colorectal cancer (CRC) is currently an urgent need in oncology.
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