Stemcell, 100-1167, Stavudine

Inhibit HIV replication and cancer cell growth with stavudine, a nucleoside analog of thymidine and HIV reverse transcriptase inhibitor (Tai-Shun et al.). After phosphorylation by kinases, stavudine turns into stavudine triphosphate, a compound that competes with the natural substrate thymidine triphosphate for incorporation into viral DNA by HIV reverse transcriptase . When stavudine triphosphate is incorporated into the viral DNA chain, it terminates DNA replication prematurely and inhibits HIV replication (Hurst & Noble).

Stavudine has been used for:

CANCER RESEARCH

· Induces mitochondrial reactive oxygen species (ROS) and enhances mitochondrial oxidative stress in human hepatoma cells (Velsor et al.).

· Reported to induce cellular senescence in human fibroblasts. Fibroblasts treated with stavudine exhibited mitochondrial dysfunction, slowed division rates, and increased ROS levels in early culture passages. In later passages, fibroblasts became senescent on the basis of p16 and p21 protein expression and senescence-associated-beta-galactosidase activity (Caron et al.).

DISEASE MODELING

· Reduces NLRP3 inflammasome-associated inflammation and stimulates Aβ autophagy by THP-1-derived macrophages in an in vitro model of Alzheimer's disease (La Rosa et al.).