Testing of Known Compounds for Cancer Treatment Efficacy

Sodium dichloroacetate (DCA) has been investigated as a novel cancer therapy since 2007 when Bonnet et al published research study demonstrating the efficacy of DCA in treating human cancers by inhibition of mitochondrial pyruvate dehydrogenase kinase (PDK). Altogen Labs, an Austin-based biotechnology and preclinical research company, performed an independent study exploring potential novel and accessible cancer treatment options based on structurally modified DCA analogues. The results of the study identified two cationic dichloric compounds, referred to as DCAH and DCMAH, as potential candidates for further investigation. The study, recently published in Cancer Biology & Therapy journal (2019, 20(9):1281-1289. doi: 10.1080/15384047.2019.1632131. Ovcharenko D et al). Two dichloric compounds inhibit in vivo U87 xenograft tumor growth), demonstrated in vivo efficacy of structurally modified analogs (DCAH and DCMAH) in U87 human glioblastoma xenograft model. The anti-tumor effect is comparable to both DCA and the well-known chemotherapy drug bevacizumab used for treatment of glioblastoma.

Dr. Dmitriy Ovcharenko, Altogen Labs CEO and corresponding author of the article, described that this work was performed in collaboration with National Cancer Institute’s Developmental Therapeutics Program. Of the three primary characteristics varied in our test compounds (charge/polarity, electron distribution, and spatial arrangement), reversing the charge compared with DCA produced the largest effect on tumor viability. While these dichloric compounds were initially investigated due to their similarity to dichloroacetate (DCA), immunoblotting results suggested a cellular pathway effect for DCAH and DCMAH independent from that of DCA. According to Altogen Labs’ senior scientist Dr. Catrina Chitjian, this work suggests the clinical potential for DCAH and DCMAH as minimally toxic anti-cancer drugs and demonstrates the importance of additional studies. Interestingly, DCAH and DCMAH are simple small molecules traditionally used as building blocks for organic chemistry synthesis, which is promising for potentially inexpensive mass production.

Two dichloric compounds inhibit in vivo U87 xenograft tumor growth