PT2977 (Synonyms: PT2977; MK-6482) |
Catalog No.GC37034
One-Click Copy Product Info
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PT2977 is an orally active and selective HIF-2α inhibitor with an IC50 of 9nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1672668-24-4
Sample solution is provided at 25 µL, 10mM.
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PT2977 is an orally active and selective HIF-2α inhibitor with an IC50 of 9nM[1]. HIF-2α is a key transcription factor regulating the expression of hypoxia response genes and plays a core role in tumor angiogenesis, stem cell maintenance and metabolic reprogramming[2]. PT2977 blocks the transcription of downstream target genes by inhibiting HIF-2α, and is mainly used in research for the treatment of clear cell renal cell carcinoma (ccRCC)[3].
In vitro, PT2977 (2μM; 48h) inhibited the dimerization of HIF-2α with HIF-1β in 786-O and A498 renal cancer cell lines, reduced the mRNA levels of VEGFA, GLUT1, and Cyclin D1, and blocked clonogenic formation in soft agar[4]. PT2977 (0-2μM; 24h) reduced the mRNA levels of HIF target genes without significant effect on cell proliferation[5].
In vivo, PT2977 (100mg/kg; p.o.; twice daily; 28 days) decreased tumor volume, reduced circulating human(graft-derived) VEGF levels, and lowered the mRNA levels of HIF-2α target genes (such as VEGFA, CCND1, GLUT1, PAI1, and CXCR4) in a 786-O cell line-derived xenograft mouse model[6]. PT2977 (30mg/kg or 100mg/kg; p.o.; twice daily; 5 days) decreased HIF-2α and Cyclin D1 protein levels, increased the number of active Caspase-3 positive cells, and promoted the apoptosis of tumor cells in tumor tissues of ccRCC xenograft tumor models[7].
References:
[1] Xu R, Wang K, Rizzi JP, et al. 3-[(1S,2S,3R)-2,3-Difluoro-1-hydroxy-7-methylsulfonylindan-4-yl]oxy-5-fluorobenzonitrile (PT2977), a Hypoxia-Inducible Factor 2α (HIF-2α) Inhibitor for the Treatment of Clear Cell Renal Cell Carcinoma. J Med Chem. 2019;62(15):6876-6893.
[2] Murugesan T, Rajajeyabalachandran G, Kumar S, Nagaraju S, Jegatheesan SK. Targeting HIF-2α as therapy for advanced cancers. Drug Discov Today. 2018;23(7):1444-1451.
[3] Wu X, Lazris D, Wong R, Tykodi SS. Belzutifan for the treatment of renal cell carcinoma. Ther Adv Med Oncol. 2025;17:17588359251317846.
[4] Hamal KB, Pavlich CI, Carlson GJ, et al. Synthesis of the Hypoxia-Inducible Factor-2α (HIF-2α) Inhibitor, 3-[(1S,2S,3R)-2,3-Difluoro-1-hydroxy-7-methylsulfonylindan-4-yl]oxy-5-fluorobenzonitrile (PT2977, Belzutifan); Efficient Replication of Established Approaches. Tetrahedron Lett. 2023;128:154691.
[5] Cho H, Du X, Rizzi JP, et al. On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models. Nature. 2016;539(7627):107-111.
[6] Chen W, Hill H, Christie A, et al. Targeting renal cell carcinoma with a HIF-2 antagonist. Nature. 2016;539(7627):112-117.
[7] Wallace, E. M., Rizzi, J. P., Hanrahan, C. F., et al. A small-molecule antagonist of HIF-2α is efficacious in preclinical models of renal cell carcinoma.
| Cell experiment [1]: | |
Cell lines | 786-O renal cancer cells |
Preparation Method | 2×105 786-O renal cancer cells were inoculated per well in 6-well plates with 3 replicates for each group. Cells were treated with 2μM PT2977 for 48 hours. Negative control group was not treated with anything. After 48 hours, cells were harvested, and RNA was extracted using TRIzol reagent following manufacturer’s instructions. RT-PCR was then performed. |
Reaction Conditions | 2μM; 48h |
Applications | PT2977 (2μM; 48h) reduced the mRNA levels of VEGFA, GLUT1, and Cyclin D1 in 786-O renal cancer cell lines. |
| Animal experiment [2]: | |
Animal models | NOD/SCID mice |
Preparation Method | 64mm3 fragments of tissue from stably growing orthotopic tumorgrafts were implanted subcutaneously in 4–6 week old female and male NOD/SCID mice. Vehicle (10% EtOH, 30% PEG400, 60% MCT [0.5% methyl cellulose, 0.5% Tween 80 (aq)]) was administered by gavage every 12h. PT2977 was administered at 100 mg/kg by oral gavage every 12h in 10% EtOH, 30% PEG400, 60% MCT for 28 consecutive days. Mouse weights were taken weekly. Tumors were generally measured twice a week using a digital caliper. |
Dosage form | 100mg/kg; p.o.; twice daily; 28 days |
Applications | PT2977 (100mg/kg; p.o.; twice daily; 28 days) decreased tumor volume in a 786-O cell line-derived xenograft mouse model. |
References: | |
| Cas No. | 1672668-24-4 | SDF | |
| Synonyms | PT2977; MK-6482 | ||
| Canonical SMILES | N#CC1=CC(F)=CC(OC2=CC=C(S(=O)(C)=O)C3=C2[C@@H](F)[C@@H](F)[C@H]3O)=C1 | ||
| Formula | C17H12F3NO4S | M.Wt | 383.34 |
| Solubility | DMSO: 50 mg/mL (130.43 mM) | Storage | Store at -20°C, stored under nitrogen |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6087 mL | 13.0433 mL | 26.0865 mL |
| 5 mM | 521.7 μL | 2.6087 mL | 5.2173 mL |
| 10 mM | 260.9 μL | 1.3043 mL | 2.6087 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 17 reference(s) in Google Scholar.)