Peringatan Keamanan

There is no information regarding the acute toxicity (LD50) or overdose profile of vorasidenib.

Vorasidenib

DB17097

small molecule approved investigational

Deskripsi

Vorasidenib is a first-in-class dual isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) inhibitor.A264209 It works by suppressing the levels of D-2-hydroxyglutarate (2-HG), an oncometabolite produced by mutant IDH1 and IDH2 isoforms.L51139 Vorasidenib displayed improved brain penetration and higher drug exposure compared to other IDH inhibitors such as ivosidenib and enasidenib.A264209

Vorasidenib was first approved by the FDA on August 6, 2024, for the treatment of Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation.L51144

Struktur Molekul 2D

Berat 414.74
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The mean (CV%) steady state terminal half-life is 10 days (57%).[L51139]
Volume Distribusi The mean (CV%) volume of distribution at steady-state of vorasidenib is 3,930 L (40%).[L51139] Vorasidenib penetrates the blood-brain barrier: The brain tumour-to-plasma concentration ratio is 1.6.[L51139]
Klirens (Clearance) The mean (CV%) steady state oral clearance is 14 L/h (56%).[L51139]

Absorpsi

Vorasidenib maximum plasma concentration (Cmax) and AUC increased approximately proportionally over the dose range of 10 to 200 mg (0.2 to 4 times the exposure of the highest approved recommended dosage) following once-daily administration of single and multiple doses. At the highest approved recommended dosage, steady-state mean (CV%) Cmax is 133 ng/mL (73%) and AUC is 1,988 h x ng/mL (95%). A steady state is achieved within 28 days of once-daily dosing, and the mean accumulation ratio of AUC is 4.4. The median (minimum, maximum) time to maximum plasma concentrations (Tmax) at steady-state is 2 hours (0.5 to 4 hours). The mean absolute bioavailability of vorasidenib is 34%.L51139 A high-fat and high-calorie (total 800-1,000 calories, of which 500-600 from fat) meal increased vorasidenib Cmax 3.1-fold and AUC 1.4-fold, compared to the fasting conditions. A low-fat and low-calorie (total 400-500 calories, of which 100-125 from fat) meal increased vorasidenib Cmax 2.3-fold and AUC 1.4-fold, compared to the fasting conditions.L51139

Metabolisme

Vorasidenib is primarily metabolized by CYP1A2 with minor contributions from CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A. Non-CYP pathways may contribute up to 30% of its metabolism.L51139 The exact metabolic pathways and metabolites have not been fully elucidated.

Rute Eliminasi

Following a single oral radiolabeled dose of vorasidenib, 85% of the dose was recovered in feces (56% unchanged) and 4.5% was recovered in urine.L51139

Interaksi Makanan

1 Data
  • 1. Take with or without food. A high-fat and high-calorie increases vorasidenib and Cmax, but not to a clinically significant extent.

Interaksi Obat

486 Data
Fluvoxamine The metabolism of Vorasidenib can be decreased when combined with Fluvoxamine.
Enoxacin The metabolism of Vorasidenib can be decreased when combined with Enoxacin.
Rofecoxib The metabolism of Vorasidenib can be decreased when combined with Rofecoxib.
Ciprofloxacin The metabolism of Vorasidenib can be decreased when combined with Ciprofloxacin.
Quinidine The metabolism of Vorasidenib can be decreased when combined with Quinidine.
Amiodarone The metabolism of Vorasidenib can be decreased when combined with Amiodarone.
Technetium Tc-99m ciprofloxacin The metabolism of Vorasidenib can be decreased when combined with Technetium Tc-99m ciprofloxacin.
Viloxazine The metabolism of Vorasidenib can be decreased when combined with Viloxazine.
Clinafloxacin The metabolism of Vorasidenib can be decreased when combined with Clinafloxacin.
Furafylline The metabolism of Vorasidenib can be decreased when combined with Furafylline.
Caffeine The metabolism of Vorasidenib can be decreased when combined with Caffeine.
Moxifloxacin The metabolism of Vorasidenib can be decreased when combined with Moxifloxacin.
Lidocaine The metabolism of Vorasidenib can be decreased when combined with Lidocaine.
Mexiletine The metabolism of Vorasidenib can be decreased when combined with Mexiletine.
Imipramine The metabolism of Vorasidenib can be decreased when combined with Imipramine.
Alosetron The metabolism of Vorasidenib can be decreased when combined with Alosetron.
Ketoconazole The metabolism of Vorasidenib can be decreased when combined with Ketoconazole.
Gatifloxacin The metabolism of Vorasidenib can be decreased when combined with Gatifloxacin.
Simeprevir The metabolism of Vorasidenib can be decreased when combined with Simeprevir.
Vemurafenib The metabolism of Vemurafenib can be increased when combined with Vorasidenib.
Zucapsaicin The metabolism of Vorasidenib can be decreased when combined with Zucapsaicin.
Lobeglitazone The metabolism of Vorasidenib can be decreased when combined with Lobeglitazone.
Curcumin The metabolism of Vorasidenib can be decreased when combined with Curcumin.
Pazufloxacin The metabolism of Vorasidenib can be decreased when combined with Pazufloxacin.
Osilodrostat The metabolism of Vorasidenib can be decreased when combined with Osilodrostat.
Rifampin The metabolism of Vorasidenib can be increased when combined with Rifampin.
Rucaparib The metabolism of Vorasidenib can be increased when combined with Rucaparib.
Cyclosporine The metabolism of Cyclosporine can be increased when combined with Vorasidenib.
Bortezomib The metabolism of Bortezomib can be increased when combined with Vorasidenib.
Dofetilide The metabolism of Dofetilide can be increased when combined with Vorasidenib.
Cabergoline The metabolism of Cabergoline can be increased when combined with Vorasidenib.
Theophylline The metabolism of Theophylline can be increased when combined with Vorasidenib.
Vindesine The metabolism of Vindesine can be increased when combined with Vorasidenib.
Dihydroergotamine The metabolism of Dihydroergotamine can be increased when combined with Vorasidenib.
Vinorelbine The metabolism of Vinorelbine can be increased when combined with Vorasidenib.
Sorafenib The metabolism of Sorafenib can be increased when combined with Vorasidenib.
Teniposide The metabolism of Teniposide can be increased when combined with Vorasidenib.
Erlotinib The metabolism of Erlotinib can be increased when combined with Vorasidenib.
Cyclophosphamide The metabolism of Cyclophosphamide can be increased when combined with Vorasidenib.
Nortriptyline The metabolism of Nortriptyline can be increased when combined with Vorasidenib.
Vincristine The metabolism of Vincristine can be increased when combined with Vorasidenib.
Methotrexate The metabolism of Methotrexate can be increased when combined with Vorasidenib.
Carbamazepine The metabolism of Carbamazepine can be increased when combined with Vorasidenib.
Vinblastine The metabolism of Vinblastine can be increased when combined with Vorasidenib.
Clonidine The metabolism of Clonidine can be increased when combined with Vorasidenib.
Astemizole The metabolism of Astemizole can be increased when combined with Vorasidenib.
Tamoxifen The metabolism of Tamoxifen can be increased when combined with Vorasidenib.
Warfarin The metabolism of Warfarin can be increased when combined with Vorasidenib.
Ergotamine The metabolism of Ergotamine can be increased when combined with Vorasidenib.
Irinotecan The metabolism of Irinotecan can be increased when combined with Vorasidenib.
Etoposide The metabolism of Etoposide can be increased when combined with Vorasidenib.
Tacrolimus The metabolism of Tacrolimus can be increased when combined with Vorasidenib.
Conivaptan The metabolism of Conivaptan can be increased when combined with Vorasidenib.
Sirolimus The metabolism of Sirolimus can be increased when combined with Vorasidenib.
Phenprocoumon The metabolism of Phenprocoumon can be increased when combined with Vorasidenib.
Doxorubicin The metabolism of Doxorubicin can be increased when combined with Vorasidenib.
Busulfan The metabolism of Busulfan can be increased when combined with Vorasidenib.
Pimozide The metabolism of Pimozide can be increased when combined with Vorasidenib.
Bicalutamide The metabolism of Bicalutamide can be increased when combined with Vorasidenib.
Ifosfamide The metabolism of Ifosfamide can be increased when combined with Vorasidenib.
Aminophylline The metabolism of Aminophylline can be increased when combined with Vorasidenib.
Levacetylmethadol The metabolism of Levacetylmethadol can be increased when combined with Vorasidenib.
Paclitaxel The metabolism of Paclitaxel can be increased when combined with Vorasidenib.
Clomipramine The metabolism of Clomipramine can be increased when combined with Vorasidenib.
Docetaxel The metabolism of Docetaxel can be increased when combined with Vorasidenib.
Dasatinib The metabolism of Dasatinib can be increased when combined with Vorasidenib.
Sunitinib The metabolism of Sunitinib can be increased when combined with Vorasidenib.
Fosphenytoin The metabolism of Fosphenytoin can be increased when combined with Vorasidenib.
Digitoxin The metabolism of Digitoxin can be increased when combined with Vorasidenib.
Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Vorasidenib.
Everolimus The metabolism of Everolimus can be increased when combined with Vorasidenib.
Thiotepa The metabolism of Thiotepa can be increased when combined with Vorasidenib.
Ixabepilone The metabolism of Ixabepilone can be increased when combined with Vorasidenib.
Dronedarone The metabolism of Dronedarone can be increased when combined with Vorasidenib.
Nilotinib The metabolism of Nilotinib can be increased when combined with Vorasidenib.
Trabectedin The metabolism of Trabectedin can be increased when combined with Vorasidenib.
Cobimetinib The metabolism of Cobimetinib can be increased when combined with Vorasidenib.
Vandetanib The metabolism of Vandetanib can be increased when combined with Vorasidenib.
Trastuzumab emtansine The metabolism of Trastuzumab emtansine can be increased when combined with Vorasidenib.
Romidepsin The metabolism of Romidepsin can be increased when combined with Vorasidenib.
Tolvaptan The metabolism of Tolvaptan can be increased when combined with Vorasidenib.
Temsirolimus The metabolism of Temsirolimus can be increased when combined with Vorasidenib.
Pazopanib The metabolism of Pazopanib can be increased when combined with Vorasidenib.
Midostaurin The metabolism of Midostaurin can be increased when combined with Vorasidenib.
Panobinostat The metabolism of Panobinostat can be increased when combined with Vorasidenib.
Bosutinib The metabolism of Bosutinib can be increased when combined with Vorasidenib.
Axitinib The metabolism of Axitinib can be increased when combined with Vorasidenib.
Cabazitaxel The metabolism of Cabazitaxel can be increased when combined with Vorasidenib.
Lomitapide The metabolism of Lomitapide can be increased when combined with Vorasidenib.
Crizotinib The metabolism of Crizotinib can be increased when combined with Vorasidenib.
Brentuximab vedotin The metabolism of Brentuximab vedotin can be increased when combined with Vorasidenib.
Ruxolitinib The metabolism of Ruxolitinib can be increased when combined with Vorasidenib.
Regorafenib The metabolism of Regorafenib can be increased when combined with Vorasidenib.
Ponatinib The metabolism of Ponatinib can be increased when combined with Vorasidenib.
Pomalidomide The metabolism of Pomalidomide can be increased when combined with Vorasidenib.
Dabrafenib The metabolism of Dabrafenib can be increased when combined with Vorasidenib.
Idelalisib The metabolism of Idelalisib can be increased when combined with Vorasidenib.
Ceritinib The metabolism of Ceritinib can be increased when combined with Vorasidenib.
Palbociclib The metabolism of Palbociclib can be increased when combined with Vorasidenib.
Olaparib The metabolism of Olaparib can be increased when combined with Vorasidenib.

Target Protein

Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial IDH3A
Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial IDH3B
Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial IDH3G
Isocitrate dehydrogenase [NADP] cytoplasmic IDH1
Isocitrate dehydrogenase [NADP], mitochondrial IDH2

Referensi & Sumber

Artikel (PubMed)
  • PMID: 32071674
    Konteatis Z, Artin E, Nicolay B, Straley K, Padyana AK, Jin L, Chen Y, Narayaraswamy R, Tong S, Wang F, Zhou D, Cui D, Cai Z, Luo Z, Fang C, Tang H, Lv X, Nagaraja R, Yang H, Su SM, Sui Z, Dang L, Yen K, Popovici-Muller J, Codega P, Campos C, Mellinghoff IK, Biller SA: Vorasidenib (AG-881): A First-in-Class, Brain-Penetrant Dual Inhibitor of Mutant IDH1 and 2 for Treatment of Glioma. ACS Med Chem Lett. 2020 Jan 22;11(2):101-107. doi: 10.1021/acsmedchemlett.9b00509. eCollection 2020 Feb 13.
  • PMID: 34078652
    Mellinghoff IK, Penas-Prado M, Peters KB, Burris HA 3rd, Maher EA, Janku F, Cote GM, de la Fuente MI, Clarke JL, Ellingson BM, Chun S, Young RJ, Liu H, Choe S, Lu M, Le K, Hassan I, Steelman L, Pandya SS, Cloughesy TF, Wen PY: Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial. Clin Cancer Res. 2021 Aug 15;27(16):4491-4499. doi: 10.1158/1078-0432.CCR-21-0611. Epub 2021 Jun 2.
  • PMID: 38760442
    Ruda R, Horbinski C, van den Bent M, Preusser M, Soffietti R: IDH inhibition in gliomas: from preclinical models to clinical trials. Nat Rev Neurol. 2024 Jul;20(7):395-407. doi: 10.1038/s41582-024-00967-7. Epub 2024 May 17.
  • PMID: 38425121
    Bombino A, Magnani M, Conti A: A Promising Breakthrough: The Potential of VORASIDENIB in the Treatment of Low-grade Glioma. Curr Mol Pharmacol. 2024 Feb 29. doi: 10.2174/0118761429290327240222061812.
  • PMID: 37272516
    Mellinghoff IK, van den Bent MJ, Blumenthal DT, Touat M, Peters KB, Clarke J, Mendez J, Yust-Katz S, Welsh L, Mason WP, Ducray F, Umemura Y, Nabors B, Holdhoff M, Hottinger AF, Arakawa Y, Sepulveda JM, Wick W, Soffietti R, Perry JR, Giglio P, de la Fuente M, Maher EA, Schoenfeld S, Zhao D, Pandya SS, Steelman L, Hassan I, Wen PY, Cloughesy TF: Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. N Engl J Med. 2023 Aug 17;389(7):589-601. doi: 10.1056/NEJMoa2304194. Epub 2023 Jun 4.

Contoh Produk & Brand

Produk: 4 • International brands: 0
Produk
  • Voranigo
    Tablet, film coated • 10 mg/1 • Oral • US • Approved
  • Voranigo
    Tablet, film coated • 40 mg/1 • Oral • US • Approved
  • Voranigo
    Tablet • 10 mg • Oral • Canada • Approved
  • Voranigo
    Tablet • 40 mg • Oral • Canada • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
© 2025 Digital Pharmacy Research - Universitas Esa Unggul