| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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PT2399 is a novel, potent, and orally bioavailable small molecule inhibitor of HIF-2 which binds to HIF-2α PAS B domain with an IC50 of 6 nM, exhibiting potent antitumor activity in vivo.. It selectively disrupts the heterodimerization of HIF-2α with HIF-1β. Preclinical and clinical data indicate that PT2399 is effective in blocking cancer cell growth, proliferation, and tumor angiogenesis characteristic in ccRCC.
| ln Vitro |
PT2399 (compound 10f) has an IC50 of 6 nM for inhibiting HIF-2α [3]. Because it inhibits HIF translocation -2α-/- 786-O cells and other cell lines tested for HIF-2α, PT2399 (20 μM) can induce off-target damage. It directly binds to the HIF-2α PAS B domain and surpasses HIF-2α's ability to connect to aryl hydrocarbon receptor nuclear transporter (ARNT) [2]. In soft agar, PT2399 (0.2-2 μM) inhibits 786-O VHL/; 0-21 days) and prevents 786-O cell development [2]. In ccRCC cells, a number of HIF target genes, including BNIP3, do not suppress HIF-1α potential targets [2].
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| ln Vivo |
PT2399 reduces tumor cell density and increases fibrosis in RCC mice [1]. PT2399 (100 mg/kg; side wall gavage; every 12 hours) is more active than SU 11248 and inhibits several interactions in RCC tumor-bearing cells PT2399 directly inhibits HIF-2α in an inhibitory manner in primary and metastatic pVHL Defective ccRCC leads to tumor regression in preclinical models [2]. SU 11248 triggers tumor growth [1].
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: 786-O cells Tested Concentrations: 0 μM, 0.2 μM, 2 μM Incubation Duration: 0-21 days Experimental Results: 0.2-2 μM concentration can inhibit the growth of 786-O cells in soft agar. |
| Animal Protocol |
Animal/Disease Models: Mouse RCC tumor graft [1]
Doses: 100 mg/kg Route of Administration: po (oral gavage); every 12 hrs (hrs (hours)) Experimental Results: More active than SU 11248, and inhibits tumor growth of a variety of SU 11248-resistant tumors . |
| References |
| Molecular Formula |
C17H10F5NO4S
|
|---|---|
| Molecular Weight |
419.322620868683
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| Exact Mass |
419.03
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| Elemental Analysis |
C, 48.69; H, 2.40; F, 22.65; N, 3.34; O, 15.26; S, 7.65
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| CAS # |
1672662-14-4
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| Related CAS # |
(Rac)-PT2399;1672662-07-5
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| PubChem CID |
91663289
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| Appearance |
White to off-white solid powder
|
| LogP |
3.3
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
734
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C1C2=C(C=CC(=C2[C@@H](C1(F)F)O)S(=O)(=O)C(F)F)OC3=CC(=CC(=C3)C#N)F
|
| InChi Key |
MXUSGDMIHGLCNC-HNNXBMFYSA-N
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| InChi Code |
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
|
| Chemical Name |
3-[(1S)-7-(Difluoromethylsulfonyl)-2,2-difluoro-1-hydroxy-indan-4-yl]oxy-5-fluoro-benzonitrile
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| Synonyms |
PT2399 PT-2399 PT 2399
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 200 mg/mL (~476.96 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (3.98 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.67 mg/mL (3.98 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.67 mg/mL (3.98 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3848 mL | 11.9241 mL | 23.8481 mL | |
| 5 mM | 0.4770 mL | 2.3848 mL | 4.7696 mL | |
| 10 mM | 0.2385 mL | 1.1924 mL | 2.3848 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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