Figure 4.

Telomerase‐targeted cancer therapeutics. 6‐Thio‐2′‐deoxyguanosine (6‐thio‐dG) is a mimetic of 2'‐deoxyguanosine, in which the oxygen atom of guanine is substituted with a sulfur atom. This compound is incorporated into telomeres in a telomerase‐dependent manner, which causes immediate crisis in telomerase‐positive cells (top). TERT promoter is used to construct oncolytic adenoviruses (lower left). Telomerase inhibitors shorten telomeres and eventually induce crisis in cancer (lower right). For example, imetelstat consists of a N3′‐P5′‐thio‐phosphoramidate 13‐mer oligonucleotide, which is complementary to the template region of TR, and a 5′ palmitoyl (C16) lipid group for enhanced cell permeability. IRES, internal ribosome entry site; ITR, inverted terminal repeat