Investigational THIO has been designed to have a ‘Telomerase-Mediated’ and Telomere-Targeted Mode of Action.

Telomerase is present in 90% of human cancer cells and contributes significantly to proliferative abilities and immortality of cancer cells. It is either absent or shows low activity in normal cells. THIO(6-thio-dG) is recognized by telomerase and incorporated into telomeres. Once incorporated, it compromises telomere structure and function, leading to ‘uncapping’ of the chromosome ends resulting in rapid tumor cell death.


Mender et al. A novel telomerase substrate precursor rapidly induces telomere dysfunction in telomerase positive cancer cells but not telomerase silent normal cells. Oncoscience. 2015 Aug 22;2(8):693-5.

Mender, et al. Induction of telomere dysfunction mediated by the telomerase substrate precursor 6-thio-2′-deoxyguanosine. Cancer Discovery. 2015 Jan;5(1):82-95.

Mender et al. Telomerase-Mediated Strategy for Overcoming Non-Small Cell Lung Cancer Targeted Therapy and Chemotherapy Resistance. Neoplasia 2018 Aug;20(8):826-837.

Reyes-Uribe et al. Exploiting TERT dependency as a therapeutic strategy for NRAS-mutant melanoma. Oncogene. 2018 Jul;37(30):4058-4072.

Sengupta et al. Induced Telomere Damage to Treat Telomerase Expressing Therapy-Resistant Pediatric Brain Tumors. Mol Cancer Ther. 2018 Jul;17(7):1504-1514.

Shay JW, Wright WE. Telomeres and telomerase: three decades of progress. Nat Rev Genet. 2019 May;20(5):299-309.

Zhang et al. Induction of Telomere Dysfunction Prolongs Disease Control of Therapy-Resistant Melanoma. Clin Cancer Res. 2018 Oct 1;24(19):4771-4784.

Zhang G, Shay JW. Inducing rapid telomere irreparable damage in telomerase-expressing cancers. Oncotarget. 2018 Nov 9;9(88):35803-35804.