PT2385

Research use only, not for human use.

PT2385 (PT-2385) is a potent, selective, and orally active antagonist of HIF2α, binds to HIF2α PAS-B domain (Kd=50 nM) and disrupts HIF2α/ARNT dimer formation.

PT2385 (PT-2385) is a potent, selective, and orally active antagonist of HIF2α, binds to HIF2α PAS-B domain (Kd=50 nM) and disrupts HIF2α/ARNT dimer formation; allosterically blocks HIF2α dimerization with the HIF1α/2α transcriptional dimerization partner ARNT/HIF1β, disrupts HIF2α, but not HIF1α, heterodimerization with ARNT in Hep3B cells; inhibits the expression of HIF2α-dependent genes, including VEGF-A, PAI-1, and cyclin D1 in ccRCC cell lines and tumor xenografts, also reduces HIF2α mRNA and protein levels in xenograft tumors.Kidney Cancer Phase 2 Clinical(In Vitro):PT-2385 (PT2385) is a selective antagonist of HIF-2 over HIF-1. PT-2385 is inactive for HIF-1α.(In Vivo):PT-2385 (30 or 100 mg/kg; oral gavage; twice daily) result in a rapid, dose-dependent tumor regression.PT-2385 (PT2385) inhibits expression of HIF-2α regulated genes in a dose dependent manner in vivo. Tumor is regressed with PT-2385 (3 and 10 mg/kg, p.o., b.i.d. dose) in 786-O xenograft. PT-2385 (1,3 and 10 mg/kg) also inhibits tumor-derived VEGFA protein levels. PT-2385 (10 mg/kg) treatment reduces proliferation (Ki67) and angiogenesis (CD-31).

PT-2385 (PT2385) is a selective antagonist of HIF-2 over HIF-1. PT-2385 is inactive for HIF-1α.

PT-2385 (30 or 100 mg/kg; oral gavage; twice daily) result in a rapid, dose-dependent tumor regression. PT-2385 (PT2385) inhibits expression of HIF-2α regulated genes in a dose dependent manner in vivo. Tumor is regressed with PT-2385 (3 and 10 mg/kg, p.o., b.i.d. dose) in 786-O xenograft. PT-2385 (1,3 and 10 mg/kg) also inhibits tumor-derived VEGFA protein levels. PT-2385 (10 mg/kg) treatment reduces proliferation (Ki67) and angiogenesis (CD-31). Animal Model:SCID/beige mice with the 786-O and A498 RCC cell lines Dosage:30 or 100 mg/kg Administration:Oral gavage; twice daily Result:Resulted in a rapid, dose-dependent tumor regression.

PT-2385

Angiogenesis

HIF/HIF Prolyl-hydroxylase

HIF/HIF Prolyl-hydroxylase

Cancer

Kidney Cancer

1672665-49-4

383.3417

C17H12F3NO4S

>98% (HPLC)

10 mM in DMSO

CS(C(C=C1)=C2C(CC(F)(F)[C@H]2O)=C1OC3=CC(C#N)=CC(F)=C3)(=O)=O

Benzonitrile, 3-[[(1S)-2,2-difluoro-2,3-dihydro-1-hydroxy-7-(methylsulfonyl)-1H-inden-4-yl]oxy]-5-fluoro-

(-20℃)

With Ice Pack

≥ 2 years