For research use only. Not for therapeutic Use.
PT2399 is a potent and selective HIF-2α antagonist, which directly binds to HIF-2α PAS B domain with an IC50 of 6 nM. PT2399 displays potent antitumor activity in vivo[1][2][3].
PT2399 (compound 10f) inhibits HIF-2α with an IC50 of 6 nM[3].
PT2399 can bind directly to the HIF-2α PAS B domain, and cripple HIF-2α’s ability to bind to Aryl hydrocarbon receptor nuclear translocator (ARNT)[2].
PT2399 (20 μM) causes off-target toxicity because it inhibits the proliferation of HIF-2α −/− 786-O cells and other cancer cell lines with undetectable HIF-2α[2].
PT2399 (0.2–2 μM; 0-21 days) inhibits 786-O cells soft agar growth[2].
PT2399 represses various HIF target genes in 786-O VHL−/− ccRCC cells, does not suppress HIF-1α-specific targets such as BNIP3[2].
PT2399 inhibits tumor cell proliferation 3.5 fold in renal cell carcinoma (RCC) bearing mice[1].
PT2399 reduces tumor cell density and increases fibrosis in RCC bearing mice[1].
PT2399 (100 mg/kg; oral gavage; every 12 hours) is more active than SU 11248, and inhibits tumor growth in several SU 11248-resistant tumors in RCC bearing mice [1].
PT2399 directly inhibits HIF-2α causes tumor regression in preclinical models of primary and metastatic pVHL-defective ccRCC in an on-target fashion[2].
| Catalog Number | I019279 |
| CAS Number | 1672662-14-4 |
| Synonyms | 3-[[(1S)-7-(difluoromethylsulfonyl)-2,2-difluoro-1-hydroxy-1,3-dihydroinden-4-yl]oxy]-5-fluorobenzonitrile |
| Molecular Formula | C17H10F5NO4S |
| Purity | ≥95% |
| InChI | InChI=1S/C17H10F5NO4S/c18-9-3-8(7-23)4-10(5-9)27-12-1-2-13(28(25,26)16(19)20)14-11(12)6-17(21,22)15(14)24/h1-5,15-16,24H,6H2/t15-/m0/s1 |
| InChIKey | MXUSGDMIHGLCNC-HNNXBMFYSA-N |
| SMILES | C1C2=C(C=CC(=C2C(C1(F)F)O)S(=O)(=O)C(F)F)OC3=CC(=CC(=C3)C#N)F |
| Reference | [1]. Chen W, et al. Targeting renal cell carcinoma with a HIF-2 antagonist. Nature. 2016 Nov 3;539(7627):112-117. [2]. Cho H, et al. On-Target Efficacy of a HIF2α Antagonist in Preclinical Kidney Cancer Models. Nature. Nature. 2016 Nov 3;539(7627):107-111. [3]. Wehn PM, et al. Design and Activity of Specific Hypoxia-Inducible Factor-2α (HIF-2α) Inhibitors for the Treatment of Clear Cell Renal Cell Carcinoma: Discovery of Clinical Candidate (S)-3-((2,2-Difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1 H-inden-4 |
