GLPBio

PT2977

Catalog No.: GC37034Purity:>98.00%Synonyms: PT2977; MK-6482
COASDSData Sheet
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.

PT2977
Cas No.: 1672668-24-4
10mM (in 1mL DMSO)In Stock
$112.00
1
1mgIn Stock
$56.00
1
5mgIn Stock
$133.00
1
10mgIn Stock
$196.00
1
25mgIn Stock
$368.00
1
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Description

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.

Protocol

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:
[1] Hamal KB, Pavlich CI, Carlson GJ, et al. Synthesis of the Hypoxia-Inducible Factor-2? (HIF-2?) 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.
[2] Chen W, Hill H, Christie A, et al. Targeting renal cell carcinoma with a HIF-2 antagonist. Nature. 2016;539(7627):112-117.

Product Documents

Purity:>98.00%Appearance:A solid
COASDSData Sheet

Chemical Properties

CAS No.
1672668-24-4
Synonyms
PT2977; MK-6482
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
Molecular Formula
C17H12F3NO4S
Molecular Weight
383.34
Solubility
DMSO: 50 mg/mL (130.43 mM)
Storage
Store at -20°C, stored under nitrogen
General tips
Select a suitable solvent according to the product solubility data. Once prepared, aliquot the stock solution to avoid repeated freeze-thaw cycles.
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
Shipping Condition
Evaluation samples are shipped with blue ice. Other available sizes are shipped at room temperature or with blue ice upon request.

CalculatorsMolarity / Dilution / Molecular Weight / Unit Conversion / In Vivo Formulation / Solubility

g/mol

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