| Description: |
PT2399 is an inhibitor of HIF2α[1]. |
| Target: |
HIF2α[1] |
| In Vivo: |
PT2399 (100 mg/kg; oral gavage; every 12 hours) is more active than Sunitinib and inhibits tumor growth in several Sunitinib-resistant tumors in renal cell carcinoma (RCC) bearing mice[2]. PT2399 inhibits tumor cell proliferation 3.5 fold in RCC bearing mice[2]. PT2399 reduces tumor cell density and increases fibrosis in RCC bearing mice[2]. Animal Model: Mice with RCC tumorgraft[2] Dosage: 100 mg/kg Administration: Oral gavage; every 12 hours Result: More active than sunitinib, and inhibited tumor growth in several sunitinib-resistant tumors. |
| In Vitro: |
PT2399 inhibits HIF2α directly causes tumor regression[1]. PT2399 binds directly to the HIF2α PAS B domain, and cripples HIF2α’s ability to bind to Aryl hydrocarbon receptor nuclear translocator (ARNT)[1]. Cell Viability Assay[1] Cell Line: 786-O cells Concentration: 0 μM, 0.2 μM, 20 μM Incubation Time: 0-15 days Result: Caused off-target toxicity because it inhibited the proliferation of HIF2α-/-786-O cells at 20 μM, and inhibited 786-O cell soft agar growth at 0.2 μM-2 μM. |
| References: |
[1]. Cho H, et al. On-Target Efficacy of a HIF2α Antagonist in Preclinical Kidney Cancer Models. Nature. 2016 Nov 3; 539(7627): 107–111.
[2]. Chen W, et al. Targeting Renal Cell Carcinoma with a HIF-2 antagonist. Nature. 2016 Nov 3; 539(7627): 112–117. |
