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Chemical Structure| 1672668-24-4 Chemical Structure| 1672668-24-4

Structure of Belzutifan
CAS No.: 1672668-24-4

Chemical Structure| 1672668-24-4

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Belzutifan is an inhibitor targeting HIF-2α, used in clear cell renal cell carcinoma (ccRCC) and other tumor studies.

Synonyms: PT2977; MK-6482

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Product Citations

Product Citations

Wang, Xuechun ; Duong, Loan ; Qin, Yujing ; Parrotta, Rossella ; Purohit, Paresh Kumar ; Fang, Yihao , et al.

Abstract: Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of kidney cancer. Loss of von Hippel–Lindau (VHL) and the consequent activation of hypoxia-inducible factor-α (HIFα, especially HIF2α) plays an essential role in ccRCC initiation and progression. The approved HIF2α inhibitor belzutifan faces the challenge of resistance, presenting an opportunity of co-targeting HIF2α and another vulnerability. This study elucidates the synthetic essentiality of TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) in VHL-deficient ccRCC, uncovering a novel reciprocal regulation between HIF2α and TRAIL. TRAIL was identified as a direct transcriptional target of HIF2α and paradoxically found to be crucial for cell proliferation, primarily by activating the p38 MAPK pathway and facilitating G1/S phase transition. Depletion of endogenous TRAIL or inhibition of HIF2α with belzutifan sensitizes ccRCC cells to recombinant TRAIL, presenting a promising avenue for combination therapy to overcome both TRAIL resistance and belzutifan resistance in treating ccRCC.

Keywords: TRAIL ; VHL ; HIF2α ; renal cell carcinoma ; belzutifan ; synthetic essentiality

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Product Details of Belzutifan

CAS No. :1672668-24-4
Formula : C17H12F3NO4S
M.W : 383.34
SMILES Code : N#CC1=CC(F)=CC(OC2=CC=C(S(=O)(C)=O)C3=C2[C@@H](F)[C@@H](F)[C@H]3O)=C1
Synonyms :
PT2977; MK-6482
MDL No. :MFCD32197212
InChI Key :LOMMPXLFBTZENJ-ZACQAIPSSA-N
Pubchem ID :117947097

Safety of Belzutifan

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Related Pathways of Belzutifan

epigenetics

Isoform Comparison

Biological Activity

Description
Belzutifan (PT2977), an orally bioavailable and selective inhibitor of HIF-2α, has an IC50 value of 9 nM. As a second-generation HIF-2α inhibitor, it offers enhanced potency and an optimized pharmacokinetic profile. Belzutifan holds promise as a treatment option for clear cell renal cell carcinoma (ccRCC)[1].

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT04924075 Pheochromocytoma/Paraganglioma... More >>|Pancreatic Neuroendocrine Tumor|Von Hippel-Lindau Disease|Advanced Gastrointestinal Stromal Tumor|HIF-2α Mutated Cancers Less << PHASE2 RECRUITING 2029-06-04 Cedars-Sinai Medical Center ( ... More >>Site 0110), Los Angeles, California, 90048, United States|University of Iowa ( Site 0104), Iowa City, Iowa, 52242, United States|Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - Developmental Therapeutics ( Site, Baltimore, Maryland, 21287, United States|National Institutes of Health ( Site 0125), Bethesda, Maryland, 20892, United States|Massachusetts General Hospital ( Site 0111), Boston, Massachusetts, 02114, United States|University of Michigan ( Site 0126), Ann Arbor, Michigan, 48109, United States|Washington University-Internal Medicine/Oncology ( Site 0124), Saint Louis, Missouri, 63110, United States|Icahn School of Medicine at Mount Sinai ( Site 0123), New York, New York, 10029, United States|Penn Medicine: University of Pennsylvania Health System-Heme/Onc ( Site 0127), Philadelphia, Pennsylvania, 19104, United States|Vanderbilt University Medical Center ( Site 0107), Nashville, Tennessee, 37232, United States|University of Texas MD Anderson Cancer Center ( Site 0112), Houston, Texas, 77030, United States|Prince of Wales Hospital-Medical Oncology ( Site 1601), Randwick, New South Wales, 2031, Australia|The Royal Melbourne Hospital ( Site 1602), Parkville, Victoria, 3050, Australia|Arthur J.E. Child Comprehensive Cancer Centre ( Site 0203), Calgary, Alberta, T2N 5G2, Canada|Princess Margaret Cancer Centre ( Site 0202), Toronto, Ontario, M5G 2M9, Canada|FALP ( Site 2200), Santiago, Region M. De Santiago, 7500921, Chile|Peking University First Hospital-Urology ( Site 1900), Beijing, Beijing, 100034, China|Sun Yat-sen University Cancer Center ( Site 1905), Guangzhou, Guangdong, 510700, China|Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 1904), Shanghai, Shanghai, 200001, China|West China Hospital of Sichuan University ( Site 1906), Cheng Du, Sichuan, 610041, China|Rigshospitalet ( Site 0304), Copenhagen, Hovedstaden, 2100, Denmark|Rigshospitalet-Department of Endocrinology ( Site 0303), Copenhagen, Hovedstaden, 2100, Denmark|Odense Universitetshospital ( Site 0302), Odense C, Syddanmark, 5000, Denmark|CHU Strasbourg-Hautepierre-Medecine Interne, Endocrinologie et Nutrition ( Site 0402), Strasbourg, Alsace, 67098, France|Institut Paoli-Calmettes-Oncology ( Site 0406), Marseille, Bouches-du-Rhone, 13009, France|Gustave Roussy ( Site 0403), Villejuif, Ile-de-France, 94805, France|H?pitaux Universitaires Paris Sud - H?pital Bicêtre ( Site 0407), Le Kremlin-Bicêtre, Paris, 94270, France|H?pital Edouard Herriot-oncologie ( Site 0405), Lyon, Rhone-Alpes, 69003, France|Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0404), Paris, 75014, France|Klinikum der Ludwig-Maximilians-Universitaet Muenchen-Department of Internal Medicine IV, Division (, München, Bayern, 80336, Germany|Comprehensive Cancer Center Mainfranken-Div. of Endocrinology and Diabetes ( Site 0500), Würzburg, Bayern, 97080, Germany|Universitaetsklinikum Freiburg ( Site 0504), Freiburg, Brandenburg, 79106, Germany|Universitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 0505), Düsseldorf, Nordrhein-Westfalen, 40225, Germany|Charité Universitaetsmedizin Berlin - Campus Mitte-Department of Endocrinology and Metabolism ( Site, Berlin, 10117, Germany|Semmelweis University-Belgyógyászati és Onkológiai Klinika Hematológia Osztály ( Site 0600), Budapest, 1083, Hungary|Sheba Medical Center-Institute of Endocrinology, Diabetes and Metabolism ( Site 1400), Ramat Gan, 5262100, Israel|Sourasky Medical Center ( Site 1401), Tel Aviv, 6423906, Israel|University of Naples Federico II-Dipartimento di Medicina Clinica e Chirurgia ( Site 0704), Naples, Campania, 80100, Italy|IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola ( Site 0708), Bologna, 40138, Italy|Azienda Ospedaliera Spedali Civili di Brescia-Oncology ( Site 0701), Brescia, 25123, Italy|Ospedale San Raffaele-Oncologia Medica ( Site 0705), Milano, 20132, Italy|Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroe, Milano, 20141, Italy|Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma ( Site 0703), Verona, 37134, Italy|Hokkaido University Hospital ( Site 1800), Sapporo, Hokkaido, 060-8648, Japan|Yokohama City University Hospital-Department of Urology ( Site 1804), Yokohama, Kanagawa, 236-0004, Japan|Kochi Medical School Hospital ( Site 1807), Nankoku, Kochi, 783-8505, Japan|National Cancer Center Hospital ( Site 1802), Chuo-ku, Tokyo, 104-0045, Japan|Kyoto University Hospital ( Site 1806), Kyoto, Japan|Tokyo Women's Medical University Adachi Medical Center ( Site 1803), Tokyo, 123-8558, Japan|Universitair Medisch Centrum Utrecht ( Site 1530), Utrecht, 3584 CX, Netherlands|Oslo Universitetssykehus Radiumhospitalet ( Site 2400), Oslo, 0424, Norway|GBUZ Republican Clinical Oncological Dispensary ( Site 0804), Ufa, Baskortostan, Respublika, 450054, Russian Federation|Saint Petersburg State University-Clinic of advanced medical technologies n. a. Nicolay I. Pirogov (, Saint Petersburg, Leningradskaya Oblast, 190020, Russian Federation|Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 0803), Saint Petersburg, Leningradskaya Oblast, 198255, Russian Federation|Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology MHRF ( Site 0801), Moscow, Moskva, 115522, Russian Federation|Endocrinology Research Center of Rosmedtechnologies-Surgery ( Site 0809), Moscow, Moskva, 117036, Russian Federation|National Cancer Centre Singapore ( Site 1700), Singapore, Central Singapore, 168583, Singapore|Hospital Universitario Central de Asturias-Medical Oncology ( Site 1101), Oviedo, Asturias, 33011, Spain|MD Anderson Cancer Center-Oncology ( Site 1102), Madrid, Madrid, Comunidad De, 28033, Spain|Hospital Universitario 12 de Octubre-Medical Oncology ( Site 1103), Madrid, Madrid, Comunidad De, 28041, Spain|Hospital Universitari Vall d'Hebron ( Site 1100), Barcelona, 08035, Spain|Skanes University Hospital Lund ( Site 1200), Lund, Skane Lan, 221 85, Sweden|Karolinska Universitetssjukhuset Solna ( Site 1202), Stockholm, Stockholms Lan, 171 76, Sweden|Akademiska sjukhuset-Blod- och tum?rsjukdomar ( Site 1201), Uppsala, Uppsala Lan, 751 85, Sweden|Sahlgrenska Universitetssjukhuset-Department of Oncology CTU Clinical Trial Unit ( Site 1204), Gothenburg, Vastra Gotalands Lan, 413 45, Sweden|Ege University Medicine of Faculty ( Site 0900), Bornova, Izmir, 35100, Turkey|Hacettepe Universitesi-oncology hospital ( Site 0901), Ankara, 06230, Turkey|Ankara Bilkent ?ehir Hastanesi. ( Site 0904), Ankara, 06800, Turkey|Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 0902), Istanbul, 34668, Turkey|Addenbrooke's Hospital ( Site 1309), Cambridge, Cambridgeshire, CB2 2QQ, United Kingdom|Royal Free Hospital ( Site 1302), London, England, NW3 2QG, United Kingdom|The Beatson West of Scotland Cancer Centre ( Site 1308), Glasgow, Glasgow City, G12 0YN, United Kingdom|Hammersmith Hospital-Medical Oncology ( Site 1304), London, London, City Of, W12 OHS, United Kingdom Less <<
NCT02974738 Advanced Solid Tumors|Solid Tu... More >>mor|Solid Carcinoma|Solid Tumor, Adult|ccRCC|RCC, Clear Cell Adenocarcinoma|RCC|Kidney Cancer|Clear Cell Renal Cell Carcinoma|Renal Cell Carcinoma, Metastatic|Renal Cell Carcinoma Recurrent|Renal Cell Carcinoma, Clear Cell Adenocarcinoma|Glioblastoma|Glioblastoma, Adult|GBM|Glioblastoma Multiforme Less << PHASE1 ACTIVE_NOT_RECRUITING 2025-04-14 -
NCT03445169 Healthy PHASE1 COMPLETED 2018-05-26 Spaulding Clinical, West Bend,... More >> Wisconsin, 53095, United States Less <<
NCT04489771 Carcinoma, Renal Cell PHASE2 ACTIVE_NOT_RECRUITING 2025-10-04 Georgetown University Medical ... More >>Center ( Site 0002), Washington, District of Columbia, 20007, United States|Univ of Miami- Sylvester Comprehensive Cancer Center ( Site 0023), Miami, Florida, 33136, United States|Norton Cancer Institute - St. Matthews ( Site 0025), Louisville, Kentucky, 40207, United States|Weinberg Cancer Institute at Franklin Square ( Site 0007), Baltimore, Maryland, 21237, United States|Cancer Partners of Nebraska ( Site 0003), Lincoln, Nebraska, 68510, United States|Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0012), Omaha, Nebraska, 68130, United States|New York Oncology Hematology P.C ( Site 0028), Albany, New York, 12206, United States|Roswell Park Cancer Institute ( Site 0038), Buffalo, New York, 14263, United States|Fox Chase Cancer Center ( Site 0026), Philadelphia, Pennsylvania, 19111, United States|Sanford Cancer Center Oncology Clinic ( Site 0031), Sioux Falls, South Dakota, 57104, United States|UT West Cancer Center ( Site 0032), Germantown, Tennessee, 38138, United States|Urology Associates ( Site 0015), Nashville, Tennessee, 37209, United States|University of Texas Southwestern Medical Center at Dallas ( Site 0004), Dallas, Texas, 75390, United States|Baylor Scott & White Medical Center - Temple ( Site 0013), Temple, Texas, 76508, United States|Huntsman Cancer Institute ( Site 0037), Salt Lake City, Utah, 84112, United States|Inova Schar Cancer Institute ( Site 0001), Fairfax, Virginia, 22031, United States|Blue Ridge Cancer Care - Roanoke ( Site 0017), Roanoke, Virginia, 24014, United States|Kadlec Clinic Hematology and Oncology ( Site 0008), Kennewick, Washington, 99336, United States|Macquarie University ( Site 1007), Macquarie University, New South Wales, 2109, Australia|Eastern Health - Box Hill Hospital ( Site 1003), Box Hill, Victoria, 3128, Australia|Peninsula Health Frankston Hospital ( Site 1001), Frankston, Victoria, 3199, Australia|GZA Sint Augustinus ( Site 2003), Wilrijk, Antwerpen, 2610, Belgium|Grand Hopital de Charleroi ( Site 2005), Charleroi, Hainaut, 6000, Belgium|CHU de Liege ( Site 2002), Liège, Liege, 4000, Belgium|UZ Gent ( Site 2004), Gent, Oost-Vlaanderen, 9000, Belgium|UZ Leuven ( Site 2001), Leuven, Vlaams-Brabant, 3000, Belgium|General Hospital of Athens "Alexandra" ( Site 1102), Athens, Attiki, 115 28, Greece|Athens University Hospital ATTIKON ( Site 1100), Chaidari, Attiki, 12 462, Greece|University General Hospital of Larissa ( Site 1101), Larissa, Thessalia, 411 10, Greece|Cork University Hospital ( Site 9053), Cork, T12 DC4A, Ireland|Tallaght University Hospital ( Site 9051), Dublin, D24 NR0A, Ireland|Soroka Medical Center ( Site 4004), Beer Sheva, 8410101, Israel|Rambam Medical Center ( Site 4001), Haifa, 3109601, Israel|Rabin Medical Center ( Site 4002), Petach Tikva, 4941492, Israel|Sourasky Medical Center ( Site 4003), Tel Aviv, 6423906, Israel|Maastricht Universitair Medisch Centrum - MUMC ( Site 5001), Maastricht, Limburg, 6202AZ, Netherlands|Antoni van Leeuwenhoek Ziekenhuis ( Site 5003), Amsterdam, Noord-Holland, 1066 CX, Netherlands|Isala klinieken ( Site 5002), Zwolle, Overijssel, 8025 AB, Netherlands|Erasmus MC ( Site 5000), Rotterdam, Zuid-Holland, 3015 GD, Netherlands|Universitair Medisch Centrum Utrecht ( Site 5004), Utrecht, 3584 CX, Netherlands|Federal state budgetary institution Russian Research Centre of radiology and nuclear medicine ( Site, Moscow, Moskva, 117997, Russian Federation|City Clinical Oncology Hospital No. 1 ( Site 6004), Moscow, Moskva, 129090, Russian Federation|Russian Scientific Center of Radiology and Surgical Technologies ( Site 6001), Saint Petersburg, Sankt-Peterburg, 197758, Russian Federation|Clinical Research Center of specialized types medical care-Oncology ( Site 6002), Saint-Petersburg, Sankt-Peterburg, 197758, Russian Federation|Royal Free London NHS Foundation Trust ( Site 9003), London, England, NW3 2QG, United Kingdom|Imperial College Healthcare NHS Trust ( Site 9004), London, London, City Of, W6 8RF, United Kingdom|Churchill Hospital ( Site 9000), Oxford, Oxfordshire, OX3 7LE, United Kingdom|Nottingham University Hospitals NHS Trust. City Hospital Campus ( Site 9001), Nottingham, NG5 1PB, United Kingdom Less <<
NCT03401788 VHL - Von Hippel-Lindau Syndro... More >>me|VHL Gene Mutation|VHL Syndrome|VHL Gene Inactivation|VHL-Associated Renal Cell Carcinoma|VHL-Associated Clear Cell Renal Cell Carcinoma Less << PHASE2 ACTIVE_NOT_RECRUITING 2026-03-29 National Institutes of Health ... More >>Clinical Center, Bethesda, Maryland, 20892, United States|Massachusetts General Hospital, Boston, Massachusetts, 02114, United States|University of Michigan, Ann Arbor, Michigan, 48109, United States|University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, 19104, United States|University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15232, United States|Vanderbilt Medical Center, Nashville, Tennessee, 37232, United States|MD Anderson Cancer Center, Houston, Texas, 77030, United States|Huntsman Cancer Institute, Salt Lake City, Utah, 84112, United States|Aarhus University Hospital, Aarhus, Denmark|Hospital Georges Pompidou, Paris, France|Cambridge University Hospital, Cambridge, United Kingdom Less <<
NCT04995484 Moderate Hepatic Impairment PHASE1 COMPLETED 2024-01-03 Orlando Clinical Research Cent... More >>er ( Site 0001), Orlando, Florida, 32809, United States|The Texas Liver Institute ( Site 0002), San Antonio, Texas, 78215, United States Less <<
NCT06677190 Ovarian Cancer|Ovarian Carcino... More >>ma Less << PHASE2 RECRUITING 2029-06-30 Brigham and Women's Hospital, ... More >>Boston, Massachusetts, 02215, United States|Dana-Farber Cancer Institute, Boston, Massachusetts, 02215, United States Less <<
NCT04994522 End Stage Renal Disease|Renal ... More >>Impairment Less << PHASE1 COMPLETED 2024-04-11 Orlando Clinical Research Cent... More >>er ( Site 0001), Orlando, Florida, 32809, United States Less <<
NCT04846920 Carcinoma, Renal Cell PHASE1 ACTIVE_NOT_RECRUITING 2026-07-21 Beth Israel Deaconess Medical ... More >>Center ( Site 1002), Boston, Massachusetts, 02215, United States|University of Michigan ( Site 1006), Ann Arbor, Michigan, 48109, United States|Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 1005), Nashville, Tennessee, 37232, United States|University of Texas MD Anderson Cancer Center-Genitourinary Medical Oncology ( Site 1007), Houston, Texas, 77030, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.61mL

0.52mL

0.26mL

13.04mL

2.61mL

1.30mL

26.09mL

5.22mL

2.61mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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