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)[1].

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> HIF/HIF Prolyl-Hydroxylase

Iron Sulfur Cluster Assembly 2 (ISCA2), HIF-1/2α[1]

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]. Western Blot Analysis[1] Cell Line: Normoxia 786-0 cells (20%O2) and hypoxic ACHN cells (or 1%O2 for final 24 h to induce HIF expression) Concentration: 0, 1, 5, 10, 25 μM Incubation Time: 24 hours Result: Decreased the protein level of HIF-2α, FTH1, ISCA2, and increased IRP2 protein level at high concentrations over 10 μM in normoxia 786-0 cells. Dcreased the HIF-2α and FTH1 levels at 1 μM in hypoxic ACHN cells. Cell Viability Assay[1] Cell Line: Normoxia 786-0 cells Concentration: 0-100 μM Incubation Time: 24 hours Result: Inhibited 786-0 cells viability by inducing ferroptosis, with an IC50 value of 22.0 μM.

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