| Name | PT2399 |
| Description | PT2399 is a first-in-class, orally available, small molecule inhibitor of HIF-2 that selectively disrupts the heterodimerization of HIF-2α with HIF-1β. PT2399 displays potent antitumor activity in vivo |
| 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[1].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[2][3]. |
| 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[2].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 [1][2]. |
| Storage | store at low temperature,store under nitrogen | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | DMSO : 200 mg/mL (476.96 mM)
|
| Keywords | Hypoxia-inducible factors | Inhibitor | PT2399 | PT-2399 | inhibit | HIF-PH | HIF/HIF Prolyl-Hydroxylase | HIFs | PT 2399 |
| Inhibitors Related | Deferoxamine Mesylate | Hydralazine hydrochloride | 1,4-DPCA | Chlorogenic Acid | Glucosamine | Hydroxycitric acid tripotassium hydrate | Glucosamine hydrochloride | Minocycline hydrochloride | Oltipraz | Acriflavine Hydrochloride | Glucosamine sulfate | Cinnamaldehyde |
| Related Compound Libraries | Glycolysis Compound Library | Reprogramming Compound Library | Bioactive Compound Library | HIF-1 Signaling Pathway Compound Library | Glutamine Metabolism Compound Library | Inhibitor Library | NO PAINS Compound Library | Bioactive Compounds Library Max | Anti-Cancer Compound Library | Anti-Cancer Active Compound Library |
United States
