PT2399

SKU: orb1309175

Description

PT2399 is a selective, orally bioavailable HIF-2α inhibitor that disrupts its dimerization with HIF-1β. It demonstrates significant antitumor efficacy in preclinical in vivo models, making it a valuable chemical probe for researching hypoxia signaling pathways in renal cell carcinoma and other cancers.

Research Area

Cardiovascular Research, Epigenetics & Chromatin, Metabolism Research

Key Properties

• CAS Number: 1672662-14-4
• MW: 419.32
• Purity: 99.45% (May vary between batches)
• Formula: C₁₇H₁₀F₅NO₄S
• SMILES: O[C@H]1c2c(CC1(F)F)c(Oc1cc(F)cc(c1)C#N)ccc2S(=O)(=O)C(F)F
• Target: HIF/HIF Prolyl-Hydroxylase,HIF
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (11.92 mM);DMSO:262.5 mg/mL (626.01 mM)

Bioactivity

• Target IC50:
  HIF2α:6 nM
• In Vivo:
  PT2399) that directly inhibits HIF-2α causes tumour regression in preclinical mouse models of primary and metastatic pVHL-defective clear cell renal cell carcinoma in an on-target fashion.PT2399 inhibits tumor cell proliferation 3.5 fold in renal cell carcinoma (RCC) bearing mice.PT2399 directly inhibits HIF-2α causes tumor regression in preclinical models of primary and metastatic pVHL-defective ccRCC in an on-target fashion.PT2399 reduces tumor cell density and increases fibrosis in RCC bearing mice.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 .
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• In Vitro:
  PT2399, a selective HIF-2 antagonist that was identified using a structure-based design approach. PT2399 dissociated HIF-2 (an obligatory heterodimer of HIF-2α-HIF-1β) in human ccRCC cells and suppressed tumorigenesis in 56% (10 out of 18) of such lines.PT2399 inhibits HIF-2α (IC50: 6 nM). PT2399 represses various HIF target genes in 786-O VHL / ccRCC cells, does not suppress HIF-1α-specific targets such as BNIP3. PT2399 can cripple HIF-2α’s ability to bind to Aryl hydrocarbon receptor nuclear translocator (ARNT). PT2399 (20 μM) induces off-target toxicity because it inhibits the proliferation of HIF-2α / 786-O cells and other cancer cell lines with undetectable HIF-2α. PT2399 (0.2–2 μM; 0-21 days) inhibits 786-O cells soft agar growth.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Inhibitor, inhibit, Hypoxia-inducible factors, HIFs, HIF-PH, HIFProlylHydroxylase, HIF-2α, HIF/HIFProlylHydroxylase, HIF/HIF ProlylHydroxylase, HIF/HIF Prolyl-Hydroxylase, HIF, HIF ProlylHydroxylase, HIF Prolyl-Hydroxylase, PT2399, PT-2399, PT 2399

Compound Identifiers

PubChem CID

91663289