Fig. 5
From: Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies
Structure and action of imetelstat (GRN163L). a Structure of imetelstat. Imetelstat is a lipid-conjugated 13-mer oligonucleotide sequence with a thio-phosphoramidate backbone. The oligonucleotide sequence is complementary to the hTR component of telomerase and is responsible for the inhibitory activity of imetelstat, whereas the thio-phosphoramidate backbone imparts resistance to the action of plasma and cellular nucleases. b Action of imetelstat. Imetelstat binds to the hTR template region at the hTERT active site with high affinity and blocks its recruitment to telomeric DNA. Imetelstat is a competitive telomerase template antagonist (not antisense that targets mRNA). Binding of imetelstat to hTR results in telomerase inhibition leading to progressively shortened telomeres