HIF-2α-IN-18
HIF-2α-IN-18 is a selective HIF-2α inhibitor with a human IC50 of 8.1 nM. HIF-2α-IN-18 binds to the HIF-2α PAS-B domain, induces conformational perturbations at the HIF-2α/ARNT dimerization interface, destabilizes the HIF-2α/ARNT heterodimer, and blocks HIF-2α-mediated transcriptional activity. HIF-2α-IN-18 inhibits hypoxia-induced expression of HIF-2α target genes EPO and SERPINE1, without inhibiting HIF-1α target genes PGK1 and PDK1. HIF-2α-IN-18 can be used for the research of clear cell renal cell carcinoma, hepatocellular carcinoma[1].
For research use only. We do not sell to patients.
- CAS No.: 2709068-47-1
- Formula: C18H8F7N3
- Molecular Weight:399.27
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
HIF-2α 8.1 nM (IC50) |
In Vitro
HIF-2α-IN-18 (Compound 13) (1 h; 45 min) potently inhibits binding to recombinant human HIF-2α PAS-B protein with an SPA IC50 of 14.8 nM[1].
HIF-2α-IN-18 (20 h) potently inhibits HIF-2α-mediated transcriptional activity in 786-O ccRCC cells with a cellular luciferase IC50 of 8.1 nM[1].
HIF-2α-IN-18 (20 h) inhibits HIF-2α-mediated transcriptional activity in 786-O ccRCC cells in 100% human serum with a cellular luciferase IC50 of 0.82 μM[1].
HIF-2α-IN-18 (0-50 μM; 20 h) inhibits HIF-2α-regulated VEGF-A secretion in 786-O ccRCC cells with an IC50 of 60 nM[1].
HIF-2α-IN-18 (0.01-10 μM; 20 h) potently and selectively inhibits hypoxia-induced HIF-2α target gene (EPO, SERPINE1) expression in Hep3B hepatocellular carcinoma cells without inhibiting HIF-1α target gene (PGK1, PDK1) expression[1].
HIF-2α-IN-18 (0.5 μM) has an in vitro intrinsic clearance of 29.2 μL/min/106 cells in human hepatocytes and 141 μL/min/106 cells in rat hepatocytes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:Hep3B hepatocellular carcinoma cells (intact VHL, functional HIF-1α and HIF-2α)
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Concentration:0.01 μM; 0.1 μM; 10 μM
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Incubation Time:20 h
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Result:Dose-dependently inhibited hypoxia-induced expression of HIF-2α target genes EPO and SERPINE1.
No robust or dose-dependent inhibition of HIF-1α target genes PGK1 and PDK1 was observed.
Maintained cell viability throughout the assay.
Parmacokinetics
| Species | Dose | Route | CL | Vss | T1/2 | MRTINF_obs |
|---|---|---|---|---|---|---|
| Rat[1] | 0.25 mg/kg | i.v. | 6.31 L/h/kg | 9.60 L/kg | 2.15 h | 1.53 h |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (male, weight 200-250 g)[1]
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Dosage:0.25 mg/kg
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Administration:i.v.; single dose
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Result:Achieved an in vivo clearance (CL) of 6.31 L/h/kg.
Reached a volume of distribution at steady state (Vss) of 9.60 L/kg.
Had an elimination half-life (T1/2) of 2.15 h.
Exhibited a mean residence time (MRTINF) of 1.53 h.
Showed plasma protein binding (PPB) of 93.1% bound.
Chemical Information
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CAS No. 2709068-47-1
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Molecular Weight 399.27
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Formula C18H8F7N3
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SMILES
F[C@@H]1C(C=C(F)C=C2C#N)=C2N(C3=CC=C(C(F)(F)F)C(F)=C3C#N)C[C@@H]1F
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Dual Luciferin reporter gene assay
Luciferin reporter gene assay is a reporting system to detect the activity of Firefly Luciferase using luciferin as a substrate, which is often used in the research of miRNA target gene verification and promoter transcriptive activity regulation. Dual luciferase usually refers to Firefly luciferase and Renilla luciferase.
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Carbohydrates and Mucins: Periodic Acid-Schiff (PAS) Staining
Periodic acid-Schiff staining detects tissue carbohydrates and mucosubstances by oxidizing carbohydrate glycol groups with periodic acid to generate aldehydes, which then react with Schiff reagent to produce a magenta reaction product; classic reports established the method for mucin and polysaccharide-containing structures in fixed tissue sections. PAS staining can demonstrate neutral mucins and goblet-cell mucin, but it is not specific for mucin because glycogen and other PAS-positive tissue components can also stain; diastase/PAS-D is used when glycogen removal is needed to distinguish glycogen-dependent PAS signal from non-glycogen PAS-positive mucosubstances.
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Liver Cancer Modeling
Liver cancer can be classified into primary liver cancer and secondary liver cancer. Secondary liver cancer is the metastatic liver cancer. Primary liver cancer includes hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and fibrolamellar HCC, of which HCC is the most common form, accounting for approximately 90% of primary liver cancers[1]. HCC mouse models include chemical agent-induced models, transplanted tumor models, and genetic engineered models.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
HIF-2α-IN-18 Related Classifications
HY-183583 Related Classifications
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