Oltipraz

Oltipraz has an inhibitory effect on HIF-1α activation in a time-dependent manner, completely abrogating HIF-1α induction at ≥10 μM concentrations, the IC₅₀ of Oltipraz for HIF-1α inhibition is 10 μM. Oltipraz is a potent Nrf2 activator. IC50 & Target: IC50: 10 μM (HIF-1α)^[1];
Nrf2^[4] In Vitro: Oltipraz inhibits HIF-1α activity and HIF-1α-dependent tumor growth, which may result from a decrease in HIF-1α stability through S6K1 inhibition in combination with an H2O2-scavenging effect. Oltipraz treatment also inhibits HIF-1α activation stimulated by either hypoxia or CoCl2. Oltipraz is a cancer chemopreventive agent and has an inhibitory effect on angiogenesis and tumor growth. [1] Oltipraz is also a competitive inhibitor of this cytochrome P450, with an apparent Ki of 10 μM. [2] In Vivo: In wild-type mice, hepatic levels of mRNA for all of the genes analyzed were significantly increased after Oltipraz treatment, with the highest increase (treated/control) for NQO1 mRNA levels (7.6-fold). The Northern blot analyses demonstrated that the observed increases in GST and NQO1 activities by Oltipraz in wild-type mice were preceded by significant elevations in RNA expression. Interestingly, mRNA levels of Nrf2 itself were increased more than 3-fold by Oltipraz treatment. [2]