HIF-1/2α-IN-1 是一种HIF-2α抑制剂，具有口服活性。HIF-1/2α-IN-1 具有 HIF-2α 抑制活性，IC50值为 0.92 μM。HIF-1/2α-IN-1 也可以降低 HIF-1α 水平。HIF-1/2α-IN-1 可用于透明细胞肾细胞癌（CCRCC）的研究。

HIF-1/2α-IN-1 is an orally active HIF-2α inhibitor. HIF-1/2α-IN-1 inhibits HIF-2α activity with an IC 50 value of 0.92 μM. HIF-1/2α-IN-1 also can decrease HIF-1α levels. HIF-1/2α-IN-1 can be used for the research of clear cell renal cell carcinoma (ccRCC) [1].

HIF-1/2α-IN-1 (compound #25) (0.01-100 μM) inhibits HIF-2α activity with an IC 50 value of 0.92 μM [1]. HIF-1/2α-IN-1 (0-10 μM, 24 h) decrease HIF-2α by inhibiting IRE-dependent translation and also inhibit HIF-1α at higher concentrations，which effects mediates by inhibiting the function of iron sulfur cluster assembly 2 (ISCA2) [1]. HIF-1/2α-IN-1 (1 μM, 24 h) targets ISCA2 and trigger the iron starvation response [1]. HIF-1/2α-IN-1 (0-100 μM, 24 h) decreased cell viability in 786-0 cells (IC 50 =1.7 μM (786-0), 10.6 μM (786-0 VHL)) and RCC4 cells (IC 50 =4.8 μM (RCC4), 71.0 μM (RCC4 VHL)) [1]. Cell Viability Assay [1] Cell Line: 786-0 cells and RCC4 cells Concentration: 0.01-100 μM Incubation Time: 24 h Result: Decreased cell viability in 786-0 cells and RCC4 cells. Western Blot Analysis [1] Cell Line: 786-0 cells and RCC10 cells Concentration: 0, 0.5, 1, 2.5, 10 μM Incubation Time: 24 h Result: Decreased HIF-2α activity and protein levels. Decreased HIF-1α levels at higher concentrations or treatment durations, but do not promote proteasomal degradation of HIF-1/2α. Inhibited the production of luciferase driven by the HIF-2α IRE (IRE-Luc). Increasesed IRP2, TFRC in dose-dependent and decreased FTH. RT-PCR [1] Cell Line: 786-0 cells Concentration: 0, 0.5, 1, 5 μM Incubation Time: 24 h Result: Resulted in a dose-dependent decrease in the transcription of HIF-2α target genes VEGFA and POU5F1, but not inhibited HIF-2α transcription.

HIF-1/2α-IN-1 (compound #25) (p.o.; 30, 60 mg/kg; daily) significantly reduced ccRCC xenograft growth in vivo [1]. Animal Model: NRG or Balb/c mice [1] (6-8 week old, male, 10 per group) Dosage: 30, 60 mg/kg Administration: p.o., daily Result: Significantly inhibited tumor growth. Had well tolerated with no significant weight loss.

C17H16N6O4

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