Peringatan Keamanan

Data regarding overdosage with belzutifan is lacking. There is no specific treatment available for belzutifan overdose - if a patient is suspected to have overdosed, immediately withhold belzutifan and institute standard supportive care. Grade 3 hypoxia has been observed at doses of 120mg twice daily and Grade 4 thrombocytopenia has been observed at doses of 240mg once daily (twice the recommended dose).^L35995

Belzutifan

DB15463

small molecule approved investigational

Deskripsi

Belzutifan is an inhibitor of hypoxia-inducible factor 2? (HIF-2?) used in the treatment of von Hippel-Lindau (VHL) disease-associated cancers.^L35995 The HIF-2? protein was first identified in the 1990s by researchers at UT Southwestern Medical Center as a key player in the growth of certain cancers.^L36105 Initially considered to be undruggable, a binding pocket was eventually discovered in the HIF-2? molecule which allowed for compounds to bind and inhibit these proteins. This discovery led to the initial development of belzutifan (at the time called PT2977), which was further developed by a spin-off company named Peloton Pharmaceuticals (which itself was eventually acquired by Merck in 2019).^L36105

Belzutifan inhibits the complexation of HIF-2? with another transcription factor, HIF-1?, a necessary step in its activation - by preventing the formation of this complex, belzutifan can slow or stop the growth of VHL-associated tumors. Belzutifan received FDA approval for the treatment of select VHL-associated cancers on August 13, 2021.^L36000

Struktur Molekul 2D

Berat 383.34

Wujud solid

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) The mean elimination half-life of belzutifan is 14 hours.[L35995]

Volume Distribusi The steady-state volume of distribution of belzutifan following oral administration is approximately 130 L.[L35995]

Klirens (Clearance) The mean clearance of belzutifan following oral administration is 7.3 L/h.[L35995]

Absorpsi

In patients with VHL disease-associated renal cell carcinoma, the mean C_max and AUC_0-24h at steady-state - which was achieved after approximately three days of therapy - were 1.3 µg/mL and 16.7 ?g•hr/mL, respectively.^L35995 The median T_max is one to two hours following oral administration.^L35995 The administration of belzutifan with food has a negligible effect on drug disposition - when given alongside a high-calorie, high-fat meal, the T_max was delayed by approximately 2 hours with no other clinically meaningful effects observed.^L35995

Metabolisme

Belzutifan is primarily metabolized by UGT2B17 and CYP2C19, and to a lesser extent by CYP3A4.^L35995

Rute Eliminasi

Data eliminasi belum tersedia.

Interaksi Makanan

1 Data

1. Take with or without food. The administration of food with belzutifan has no clinically meaningful effect on its disposition.

Interaksi Obat

379 Data

Darbepoetin alfa	The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Belzutifan.
Erythropoietin	The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Belzutifan.
Peginesatide	The risk or severity of Thrombosis can be increased when Peginesatide is combined with Belzutifan.
Methoxy polyethylene glycol-epoetin beta	The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Belzutifan.
Somatotropin	The serum concentration of Belzutifan can be increased when it is combined with Somatotropin.
Fluvoxamine	The serum concentration of Belzutifan can be increased when it is combined with Fluvoxamine.
Bortezomib	The serum concentration of Bortezomib can be decreased when it is combined with Belzutifan.
Fluconazole	The serum concentration of Belzutifan can be increased when it is combined with Fluconazole.
Sildenafil	The serum concentration of Belzutifan can be increased when it is combined with Sildenafil.
Ticlopidine	The serum concentration of Belzutifan can be increased when it is combined with Ticlopidine.
Pantoprazole	The serum concentration of Belzutifan can be increased when it is combined with Pantoprazole.
Citalopram	The serum concentration of Belzutifan can be increased when it is combined with Citalopram.
Sulfanilamide	The serum concentration of Belzutifan can be increased when it is combined with Sulfanilamide.
Topiramate	The serum concentration of Belzutifan can be increased when it is combined with Topiramate.
Valproic acid	The serum concentration of Belzutifan can be increased when it is combined with Valproic acid.
Amitriptyline	The serum concentration of Belzutifan can be increased when it is combined with Amitriptyline.
Indomethacin	The serum concentration of Belzutifan can be increased when it is combined with Indomethacin.
Olanzapine	The serum concentration of Belzutifan can be increased when it is combined with Olanzapine.
Omeprazole	The serum concentration of Belzutifan can be increased when it is combined with Omeprazole.
Clozapine	The serum concentration of Belzutifan can be increased when it is combined with Clozapine.
Progesterone	The serum concentration of Belzutifan can be increased when it is combined with Progesterone.
Sorafenib	The serum concentration of Sorafenib can be decreased when it is combined with Belzutifan.
Chloramphenicol	The serum concentration of Belzutifan can be increased when it is combined with Chloramphenicol.
Lansoprazole	The serum concentration of Belzutifan can be increased when it is combined with Lansoprazole.
Imipramine	The serum concentration of Belzutifan can be increased when it is combined with Imipramine.
Quinine	The serum concentration of Belzutifan can be increased when it is combined with Quinine.
Fluoxetine	The serum concentration of Belzutifan can be increased when it is combined with Fluoxetine.
Cimetidine	The serum concentration of Belzutifan can be increased when it is combined with Cimetidine.
Ritonavir	The serum concentration of Belzutifan can be increased when it is combined with Ritonavir.
Mephenytoin	The serum concentration of Belzutifan can be increased when it is combined with Mephenytoin.
Zafirlukast	The serum concentration of Belzutifan can be increased when it is combined with Zafirlukast.
Carbamazepine	The serum concentration of Carbamazepine can be decreased when it is combined with Belzutifan.
Voriconazole	The serum concentration of Belzutifan can be increased when it is combined with Voriconazole.
Nicardipine	The serum concentration of Belzutifan can be increased when it is combined with Nicardipine.
Efavirenz	The serum concentration of Belzutifan can be increased when it is combined with Efavirenz.
Nilutamide	The serum concentration of Belzutifan can be increased when it is combined with Nilutamide.
Aprepitant	The serum concentration of Belzutifan can be increased when it is combined with Aprepitant.
Warfarin	The serum concentration of Warfarin can be decreased when it is combined with Belzutifan.
Amprenavir	The serum concentration of Belzutifan can be increased when it is combined with Amprenavir.
Delavirdine	The serum concentration of Belzutifan can be increased when it is combined with Delavirdine.
Esomeprazole	The serum concentration of Belzutifan can be increased when it is combined with Esomeprazole.
Modafinil	The serum concentration of Belzutifan can be increased when it is combined with Modafinil.
Tranylcypromine	The serum concentration of Belzutifan can be increased when it is combined with Tranylcypromine.
Methimazole	The serum concentration of Belzutifan can be increased when it is combined with Methimazole.
Oxcarbazepine	The serum concentration of Belzutifan can be increased when it is combined with Oxcarbazepine.
Phenelzine	The serum concentration of Belzutifan can be increased when it is combined with Phenelzine.
Diazepam	The serum concentration of Belzutifan can be increased when it is combined with Diazepam.
Ethanol	The serum concentration of Belzutifan can be increased when it is combined with Ethanol.
Zonisamide	The serum concentration of Belzutifan can be increased when it is combined with Zonisamide.
Buprenorphine	The serum concentration of Belzutifan can be increased when it is combined with Buprenorphine.
Tipranavir	The serum concentration of Belzutifan can be increased when it is combined with Tipranavir.
Felbamate	The serum concentration of Belzutifan can be increased when it is combined with Felbamate.
Isoniazid	The serum concentration of Belzutifan can be increased when it is combined with Isoniazid.
Telmisartan	The serum concentration of Belzutifan can be increased when it is combined with Telmisartan.
Ethinylestradiol	The serum concentration of Belzutifan can be increased when it is combined with Ethinylestradiol.
Letrozole	The serum concentration of Belzutifan can be increased when it is combined with Letrozole.
Tioconazole	The serum concentration of Belzutifan can be increased when it is combined with Tioconazole.
Ketoconazole	The serum concentration of Belzutifan can be increased when it is combined with Ketoconazole.
Probenecid	The serum concentration of Belzutifan can be increased when it is combined with Probenecid.
Fenofibrate	The serum concentration of Belzutifan can be increased when it is combined with Fenofibrate.
Thalidomide	The serum concentration of Belzutifan can be increased when it is combined with Thalidomide.
Memantine	The serum concentration of Belzutifan can be increased when it is combined with Memantine.
Dimethyl sulfoxide	The serum concentration of Belzutifan can be increased when it is combined with Dimethyl sulfoxide.
Fluvastatin	The serum concentration of Belzutifan can be increased when it is combined with Fluvastatin.
Sertraline	The serum concentration of Belzutifan can be increased when it is combined with Sertraline.
Miconazole	The serum concentration of Belzutifan can be increased when it is combined with Miconazole.
Bicalutamide	The serum concentration of Bicalutamide can be decreased when it is combined with Belzutifan.
Rabeprazole	The serum concentration of Belzutifan can be increased when it is combined with Rabeprazole.
Moclobemide	The serum concentration of Belzutifan can be increased when it is combined with Moclobemide.
Gemfibrozil	The serum concentration of Belzutifan can be increased when it is combined with Gemfibrozil.
Clomipramine	The serum concentration of Clomipramine can be decreased when it is combined with Belzutifan.
Aminophenazone	The serum concentration of Belzutifan can be increased when it is combined with Aminophenazone.
Antipyrine	The serum concentration of Belzutifan can be increased when it is combined with Antipyrine.
Etoricoxib	The serum concentration of Belzutifan can be increased when it is combined with Etoricoxib.
Topiroxostat	The serum concentration of Belzutifan can be increased when it is combined with Topiroxostat.
Oritavancin	The serum concentration of Belzutifan can be increased when it is combined with Oritavancin.
Clevidipine	The serum concentration of Belzutifan can be increased when it is combined with Clevidipine.
Methsuximide	The serum concentration of Belzutifan can be increased when it is combined with Methsuximide.
Abiraterone	The serum concentration of Belzutifan can be increased when it is combined with Abiraterone.
Dovitinib	The serum concentration of Belzutifan can be increased when it is combined with Dovitinib.
Cenobamate	The serum concentration of Belzutifan can be increased when it is combined with Cenobamate.
Sitaxentan	The serum concentration of Belzutifan can be increased when it is combined with Sitaxentan.
Armodafinil	The serum concentration of Belzutifan can be increased when it is combined with Armodafinil.
Etravirine	The serum concentration of Belzutifan can be increased when it is combined with Etravirine.
Avasimibe	The serum concentration of Belzutifan can be increased when it is combined with Avasimibe.
Lonafarnib	The serum concentration of Belzutifan can be increased when it is combined with Lonafarnib.
Safinamide	The serum concentration of Belzutifan can be increased when it is combined with Safinamide.
Nilvadipine	The serum concentration of Belzutifan can be increased when it is combined with Nilvadipine.
Gestodene	The serum concentration of Belzutifan can be increased when it is combined with Gestodene.
Seproxetine	The serum concentration of Belzutifan can be increased when it is combined with Seproxetine.
Dabrafenib	The serum concentration of Dabrafenib can be decreased when it is combined with Belzutifan.
Luliconazole	The serum concentration of Belzutifan can be increased when it is combined with Luliconazole.
Cannabidiol	The serum concentration of Belzutifan can be increased when it is combined with Cannabidiol.
Stiripentol	The serum concentration of Belzutifan can be increased when it is combined with Stiripentol.
Eslicarbazepine acetate	The serum concentration of Belzutifan can be increased when it is combined with Eslicarbazepine acetate.
Zucapsaicin	The serum concentration of Belzutifan can be increased when it is combined with Zucapsaicin.
Dosulepin	The serum concentration of Belzutifan can be increased when it is combined with Dosulepin.
Lobeglitazone	The serum concentration of Belzutifan can be increased when it is combined with Lobeglitazone.
Manidipine	The serum concentration of Belzutifan can be increased when it is combined with Manidipine.
Methylene blue	The serum concentration of Belzutifan can be increased when it is combined with Methylene blue.

Target Protein

Endothelial PAS domain-containing protein 1 EPAS1

Referensi & Sumber

Synthesis reference: Xu R, Wang K, Rizzi JP, Huang H, Grina JA, Schlachter ST, Wang B, Wehn PM, Yang H, Dixon DD, Czerwinski RM, Du X, Ged EL, Han G, Tan H, Wong T, Xie S, Josey JA, Wallace EM: 3-(1S,2S,3R)-2,3-Difluoro-1-hydroxy-7-methylsulfonylindan-4-yloxy-5-fluorobenzo nitrile (PT2977), a Hypoxia-Inducible Factor 2alpha (HIF-2alpha) Inhibitor for the Treatment of Clear Cell Renal Cell Carcinoma. J Med Chem. 2019 Aug 8;62(15):6876-6893. doi: 10.1021/acs.jmedchem.9b00719. Epub 2019 Jul 8.

Link

Contoh Produk & Brand

Produk: 2 • International brands: 1

Produk

Welireg

Tablet • 40 mg • Oral • Canada • Approved
Welireg

Tablet, film coated • 40 mg/1 • Oral • US • Approved

International Brands

Welireg — Merck

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.