HIF-1/2α-IN-2

HIF-1/2α-IN-2 is an inhibitor of HIF-1/2α. HIF-1/2α-IN-2 decrease HIF-1/2α levels and induces iron starvation response by targeting Iron Sulfur Cluster Assembly 2 (ISCA2).

HIF-1/2α-IN-2 (compound #1) (0-25 μM; 24 h) decreases HIF-2α translation instead of transcription, with a downward trend in VEGFA and POU5F1 (HIF-2α target genes) transcription and insignificant effect on EPAS1 (HIF-2α)[1].HIF-1/2α-IN-2 (0-100 μM, 24 h) inhibits the production of luciferase driven by the HIF-2α Iron-Responsive Element (IRE) luciferase reporter with an IC50 value of 3.9 μM, to block IRE-dependent translation of HIF-2α[1].HIF-1/2α-IN-2 (0, 10, 50 μM) protects ISCA2 from Pronase-mediated (4 μg/mL) degradation, and (1.5 μM; 24 h) targets ISCA2 to induce iron and metals accumulation in normoxia 786-0 cells[1]. HIF-1/2α-IN-2 (0-100 μM; 24 h) results ISCA2 inhibition and promotes cell death via ferroptosis[1].

References:
[1]. Green YS, et al. ISCA2 inhibition decreases HIF and induces ferroptosis in clear cell renal carcinoma. Oncogene. 2022 Sep 12.