Peringatan Keamanan

Toxicity information regarding olutasidenib is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as differentiation syndrome and hepatotoxicity.L44256 Symptomatic and supportive measures are recommended. In vivo studies evaluating the carcinogenicity of olutasidenib have not been performed. Olutasidenib was not genotoxic in the in vitro bacterial reverse mutation and human lymphocyte micronucleus assays, nor in the in vivo rat bone marrow micronucleus assay. The effect of olutasidenib on fertility has not been evaluated. In vitro and in vivo studies showed that olutasidenib was phototoxic. Pigmented rats given olutasidenib orally for 3 consecutive days and exposed to UV light 2 hours after the last dose developed skin erythema that persisted for 72 hours.L44256

Olutasidenib

DB16267

small molecule approved investigational

Deskripsi

Olutasidenib (FT-2102) is a selective and potent isocitrate dehydrogenase-1 (IDH1) inhibitor approved by the FDA in December 2022.L44256,L44261 It is indicated for the treatment of relapsed or refractory acute myeloid leukemia (AML) in patients with a susceptible IDH1 mutation as determined by an FDA-approved test.L44256 IDH1 mutations are common in different types of cancer, such as gliomas, AML, intrahepatic cholangiocarcinoma, chondrosarcoma, and myelodysplastic syndromes (MDS), and they lead to an increase in 2-hydroxyglutarate (2-HG), a metabolite that participates in tumerogenesis.A254726,A254731 Olutasidenib inhibits the mutated IDH1 specifically, and provides a therapeutic benefit in IDH1-mutated cancers.A254726,L44256

Other IDH1 inhibitors, such as ivosidenib, have also been approved for the treatment of relapsed or refractory AML.A254736,A254741 Olutasidenib is orally bioavailable and capable of penetrating the blood-brain barrier, and is also being evaluated for the treatment of myelodysplastic syndrome (MDS), as well as solid tumors and gliomas (NCT03684811).A254741

Struktur Molekul 2D

Berat 354.79
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) Olutasidenib has a mean half-life of 67 hours.[L44256]
Volume Distribusi Olutasidenib has an apparent volume of distribution of 319 L.[L44256]
Klirens (Clearance) Olutasidenib has a mean apparent oral clearance (CL/F) of 4 L/h.[L44256]

Absorpsi

In patients with acute myeloid leukemia (AML) given the recommended dosage, the steady-state daily area under the plasma drug concentration over time curve (AUC0-12-h, ss) of olutasidenib is 43050 ng?h/mL, and its steady-state Cmax is 3573 ng/mL. The Cmax and AUC of olutasidenib increase in a less-than proportionally manner between 100 mg and 300 mg (0.33 to 1 time the recommended total daily dose); however, no changes in the recommended dosage are required. In patients given a single oral dose of 150 mg, the median tmax of olutasidenib is approximately 4 hours. In healthy subjects, the administration of a single dose (150 mg) of olutasidenib with a high-fat meal (800-1,000 calories, 50% of total caloric content of the meal from fat) leads to a 191% and 83% increase of the Cmax and AUCinf, respectively.L44256

Metabolisme

Olutasidenib is metabolized through N-dealkylation, demethylation, oxidative deamination followed by oxidation, and mono-oxidation with subsequent glucuronidation. Approximately 90% of the olutasidenib dose is metabolized by CYP3A4, while CYP2C8, CYP2C9, CYP1A2, and CYP2C19 play a minor role.L44256

Rute Eliminasi

In healthy subjects given a single dose (150 mg) of radiolabeled olutasidenib orally, approximately 17% of olutasidenib was recovered in urine (1% unchanged), while 75% was recovered in feces (35% unchanged).L44256

Interaksi Makanan

1 Data
  • 1. Take on an empty stomach. The administration of olutasidenib with a high-fat meal increases drug exposure. Take on an empty stomach at least 1 hour before or 2 hours after a meal.

Interaksi Obat

367 Data
Darbepoetin alfa The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Olutasidenib.
Erythropoietin The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Olutasidenib.
Peginesatide The risk or severity of Thrombosis can be increased when Peginesatide is combined with Olutasidenib.
Methoxy polyethylene glycol-epoetin beta The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Olutasidenib.
Lidocaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Lidocaine.
Ropivacaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Ropivacaine.
Bupivacaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Bupivacaine.
Cinchocaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Cinchocaine.
Dyclonine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Dyclonine.
Procaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Procaine.
Prilocaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Prilocaine.
Proparacaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Proparacaine.
Meloxicam The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Meloxicam.
Oxybuprocaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Oxybuprocaine.
Cocaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Cocaine.
Mepivacaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Mepivacaine.
Levobupivacaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Levobupivacaine.
Diphenhydramine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Diphenhydramine.
Benzocaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Benzocaine.
Chloroprocaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Chloroprocaine.
Phenol The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Phenol.
Tetrodotoxin The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Tetrodotoxin.
Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Benzyl alcohol.
Capsaicin The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Capsaicin.
Etidocaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Etidocaine.
Articaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Articaine.
Tetracaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Tetracaine.
Propoxycaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Propoxycaine.
Pramocaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Pramocaine.
Butamben The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Butamben.
Butacaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Butacaine.
Oxetacaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Oxetacaine.
Ethyl chloride The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Ethyl chloride.
Butanilicaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Butanilicaine.
Metabutethamine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Metabutethamine.
Quinisocaine The risk or severity of methemoglobinemia can be increased when Olutasidenib is combined with Quinisocaine.
Phenytoin The therapeutic efficacy of Olutasidenib can be decreased when used in combination with Phenytoin.
Pentobarbital The therapeutic efficacy of Olutasidenib can be decreased when used in combination with Pentobarbital.
Carbamazepine The therapeutic efficacy of Olutasidenib can be decreased when used in combination with Carbamazepine.
Mitotane The therapeutic efficacy of Olutasidenib can be decreased when used in combination with Mitotane.
Primidone The therapeutic efficacy of Olutasidenib can be decreased when used in combination with Primidone.
Rimexolone The therapeutic efficacy of Olutasidenib can be decreased when used in combination with Rimexolone.
Rifampin The therapeutic efficacy of Olutasidenib can be decreased when used in combination with Rifampicin.
Phenobarbital The therapeutic efficacy of Olutasidenib can be decreased when used in combination with Phenobarbital.
Rifapentine The therapeutic efficacy of Olutasidenib can be decreased when used in combination with Rifapentine.
Dexamethasone The therapeutic efficacy of Olutasidenib can be decreased when used in combination with Dexamethasone.
Fosphenytoin The therapeutic efficacy of Olutasidenib can be decreased when used in combination with Fosphenytoin.
St. John's Wort The therapeutic efficacy of Olutasidenib can be decreased when used in combination with St. John's Wort.
Midostaurin The therapeutic efficacy of Olutasidenib can be decreased when used in combination with Midostaurin.
Enzalutamide The therapeutic efficacy of Olutasidenib can be decreased when used in combination with Enzalutamide.
Lumacaftor The therapeutic efficacy of Olutasidenib can be decreased when used in combination with Lumacaftor.
Apalutamide The therapeutic efficacy of Olutasidenib can be decreased when used in combination with Apalutamide.
Sildenafil The therapeutic efficacy of Sildenafil can be decreased when used in combination with Olutasidenib.
Eletriptan The therapeutic efficacy of Eletriptan can be decreased when used in combination with Olutasidenib.
Indinavir The therapeutic efficacy of Indinavir can be decreased when used in combination with Olutasidenib.
Lovastatin The therapeutic efficacy of Lovastatin can be decreased when used in combination with Olutasidenib.
Nisoldipine The therapeutic efficacy of Nisoldipine can be decreased when used in combination with Olutasidenib.
Alprazolam The therapeutic efficacy of Alprazolam can be decreased when used in combination with Olutasidenib.
Buspirone The therapeutic efficacy of Buspirone can be decreased when used in combination with Olutasidenib.
Darifenacin The therapeutic efficacy of Darifenacin can be decreased when used in combination with Olutasidenib.
Simvastatin The therapeutic efficacy of Simvastatin can be decreased when used in combination with Olutasidenib.
Aprepitant The therapeutic efficacy of Aprepitant can be decreased when used in combination with Olutasidenib.
Midazolam The therapeutic efficacy of Midazolam can be decreased when used in combination with Olutasidenib.
Eplerenone The therapeutic efficacy of Eplerenone can be decreased when used in combination with Olutasidenib.
Alfentanil The therapeutic efficacy of Alfentanil can be decreased when used in combination with Olutasidenib.
Tadalafil The therapeutic efficacy of Tadalafil can be decreased when used in combination with Olutasidenib.
Vardenafil The therapeutic efficacy of Vardenafil can be decreased when used in combination with Olutasidenib.
Tacrolimus The therapeutic efficacy of Tacrolimus can be decreased when used in combination with Olutasidenib.
Conivaptan The therapeutic efficacy of Conivaptan can be decreased when used in combination with Olutasidenib.
Sirolimus The therapeutic efficacy of Sirolimus can be decreased when used in combination with Olutasidenib.
Triazolam The therapeutic efficacy of Triazolam can be decreased when used in combination with Olutasidenib.
Tipranavir The therapeutic efficacy of Tipranavir can be decreased when used in combination with Olutasidenib.
Felodipine The therapeutic efficacy of Felodipine can be decreased when used in combination with Olutasidenib.
Atorvastatin The therapeutic efficacy of Atorvastatin can be decreased when used in combination with Olutasidenib.
Pimozide The therapeutic efficacy of Pimozide can be decreased when used in combination with Olutasidenib.
Budesonide The therapeutic efficacy of Budesonide can be decreased when used in combination with Olutasidenib.
Quetiapine The therapeutic efficacy of Quetiapine can be decreased when used in combination with Olutasidenib.
Saquinavir The therapeutic efficacy of Saquinavir can be decreased when used in combination with Olutasidenib.
Dasatinib The therapeutic efficacy of Dasatinib can be decreased when used in combination with Olutasidenib.
Darunavir The therapeutic efficacy of Darunavir can be decreased when used in combination with Olutasidenib.
Colchicine The therapeutic efficacy of Colchicine can be decreased when used in combination with Olutasidenib.
Everolimus The therapeutic efficacy of Everolimus can be decreased when used in combination with Olutasidenib.
Maraviroc The therapeutic efficacy of Maraviroc can be decreased when used in combination with Olutasidenib.
Dronedarone The therapeutic efficacy of Dronedarone can be decreased when used in combination with Olutasidenib.
Tolvaptan The therapeutic efficacy of Tolvaptan can be decreased when used in combination with Olutasidenib.
Rivaroxaban The therapeutic efficacy of Rivaroxaban can be decreased when used in combination with Olutasidenib.
Avanafil The serum concentration of Avanafil can be increased when it is combined with Olutasidenib.
Lurasidone The therapeutic efficacy of Lurasidone can be decreased when used in combination with Olutasidenib.
Ticagrelor The therapeutic efficacy of Ticagrelor can be decreased when used in combination with Olutasidenib.
Lomitapide The therapeutic efficacy of Lomitapide can be decreased when used in combination with Olutasidenib.
Rilpivirine The serum concentration of Rilpivirine can be decreased when it is combined with Olutasidenib.
Eliglustat The therapeutic efficacy of Eliglustat can be decreased when used in combination with Olutasidenib.
Naloxegol The therapeutic efficacy of Naloxegol can be decreased when used in combination with Olutasidenib.
Ibrutinib The therapeutic efficacy of Ibrutinib can be decreased when used in combination with Olutasidenib.
Ivabradine The therapeutic efficacy of Ivabradine can be decreased when used in combination with Olutasidenib.
Venetoclax The therapeutic efficacy of Venetoclax can be decreased when used in combination with Olutasidenib.
Isavuconazole The therapeutic efficacy of Isavuconazole can be decreased when used in combination with Olutasidenib.
Ebastine The therapeutic efficacy of Ebastine can be decreased when used in combination with Olutasidenib.
Lemborexant The serum concentration of Lemborexant can be decreased when it is combined with Olutasidenib.
Mobocertinib The therapeutic efficacy of Mobocertinib can be decreased when used in combination with Olutasidenib.

Target Protein

Isocitrate dehydrogenase [NADP] cytoplasmic IDH1

Referensi & Sumber

Synthesis reference: Caravella JA, et al. Structure-Based Design and Identification of FT-2102 (Olutasidenib), a Potent Mutant-Selective IDH1 Inhibitor. J Med Chem. 2020 Feb 27;63(4):1612-1623. doi: 10.1021/acs.jmedchem.9b01423. Epub 2020 Feb 12.
Artikel (PubMed)
  • PMID: 31971798
    Caravella JA, Lin J, Diebold RB, Campbell AM, Ericsson A, Gustafson G, Wang Z, Castro J, Clarke A, Gotur D, Josephine HR, Katz M, Kershaw M, Yao L, Toms AV, Barr KJ, Dinsmore CJ, Walker D, Ashwell S, Lu W: Structure-Based Design and Identification of FT-2102 (Olutasidenib), a Potent Mutant-Selective IDH1 Inhibitor. J Med Chem. 2020 Feb 27;63(4):1612-1623. doi: 10.1021/acs.jmedchem.9b01423. Epub 2020 Feb 12.
  • PMID: -
    de la Fuente MI, Colman H, Rosenthal M, Van Tine BA, Levacic D, Walbert T, Gan HK, Vieito M, Milhem MM, Lipford K, Forsyth S, Guichard SM, Mikhailov Y, Sedkov A, Brevard J, Kelly PF, Mohamed H, Monga V: Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: a multicenter, open-label, phase 1b/2 trial Neuro-oncology.
  • PMID: 31660152
    Liu X, Gong Y: Isocitrate dehydrogenase inhibitors in acute myeloid leukemia. Biomark Res. 2019 Oct 22;7:22. doi: 10.1186/s40364-019-0173-z. eCollection 2019.
  • PMID: 32829036
    de Nigris F, Ruosi C, Napoli C: Clinical efficiency of epigenetic drugs therapy in bone malignancies. Bone. 2021 Feb;143:115605. doi: 10.1016/j.bone.2020.115605. Epub 2020 Aug 20.

Contoh Produk & Brand

Produk: 1 • International brands: 1
Produk
  • Rezlidhia
    Capsule • 150 mg/1 • Oral • US • Approved
International Brands
  • Rezlidhia — Forma Therapeutics

Sekuens Gen/Protein (FASTA)

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