Peringatan Keamanan

There are no data regarding overdosage with asciminib. The effects associated with overdosage are likely to be consistent with the adverse effect profile of asciminib, and may therefore include significant hematological abnormalities and/or gastrointestinal effects, amongst others.L38995

Asciminib

DB12597

small molecule approved investigational

Deskripsi

Asciminib is a tyrosine kinase inhibitor (TKI) used in the treatment of chronic-phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). More specifically, it is an inhibitor of the ABL1 kinase activity of the BCR-ABL1 fusion proteinL38995 which serves as a driver of CML proliferation in most patients with the disease.L39005 It has also shown benefit in Ph+ CML with the T315I mutation, which produces a mutant BCR-ABL1 which is typically treatment-resistant as compared to wild-type BCR-ABL1.

Existing inhibitors of ABL compete at the ATP binding sites of these proteins and can be classified into those that target the active conformation of the kinase domain (dasatinib, bosutinib) and those that target the inactive kinase domain (imatinib, nilotinib, ponatinib).A241065 Asciminib is unique in that it acts as an allosteric inhibitor, binding at the myristoyl pocket of the BCR-ABL1 protein and locking it into an inactive conformation.L38995,A241055

Asciminib received FDA approval on October 29, 2021 (Scemblix, Novartis AG).L39000

Struktur Molekul 2D

Berat 449.84
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The terminal elimination half-life asciminib is 5.5 hours when administered at 40mg twice daily and 9.0 hours when administered at 200mg twice daily.[L38995]
Volume Distribusi At steady-state, the apparent volume of distribution of asciminib is 151 L.[L38995]
Klirens (Clearance) The total apparent clearance of asciminib is 6.7 L/h at a total daily dose of 80mg and 4.1 L/h at a dose of 200mg twice daily.[L38995]

Absorpsi

The median Tmax of asciminib following oral administration is 2.5 hours.L38995 At a dose of 80mg once daily, the steady-state Cmax and AUCtau were 1781 ng/mL and 15112 ng.h/mL, respectively. At a dose of 40mg twice daily, the steady-state Cmax and AUCtau were 793 ng/mL and 5262 ng.h/mL, respectively. At a dose of 200mg twice daily (for treatment of T315I mutants), the steady-state Cmax and AUCtau were 5642 ng/mL and 37547 ng.h/mL, respectively.L38995 As compared to the fasted state, the co-administration of asciminib with a high-fat meal decreased the AUC and Cmax by 62% and 68%, respectively, and its co-administration with a low-fat meal decreased the AUC and Cmax by 30% and 35%, respectively.L38995

Metabolisme

Asciminib is negligibly metabolized, with unchanged parent drug comprising the main drug component in plasma (~93%) and following excretion (~57% in feces).L38995 The main circulating metabolites are M30.5, M44, and M29.5, accounting for approximately 5%, 2%, and 0.4% of the total administered dose, respectively.A241035 The oxidative metabolism of asciminib is mediated by CYP3A4, and the glucuronidation of asciminib is mediated by UGT2B7 and UGT2B17.L38995

Rute Eliminasi

Asciminib is eliminated via biliary secretion facilitated by breast cancer-resistant protein (BCRP) transporters.L38995 Following oral administration, approximately 80% and 11% of an asciminib dose was recovered in the feces and urine, respectively.L38995 Unchanged parent drug accounted for 57% of drug material recovered in the feces and 2.5% in the urine.L38995

Interaksi Makanan

1 Data
  • 1. Take on an empty stomach. Avoid food consumption for at least 2 hours before and 1 hour after taking asciminib.

Interaksi Obat

636 Data
Afatinib The serum concentration of Afatinib can be increased when it is combined with Asciminib.
Bosutinib The serum concentration of Bosutinib can be increased when it is combined with Asciminib.
Brentuximab vedotin The serum concentration of Brentuximab vedotin can be increased when it is combined with Asciminib.
Colchicine The serum concentration of Colchicine can be increased when it is combined with Asciminib.
Edoxaban The serum concentration of Edoxaban can be increased when it is combined with Asciminib.
Ledipasvir The serum concentration of Ledipasvir can be increased when it is combined with Asciminib.
Naloxegol The serum concentration of Naloxegol can be increased when it is combined with Asciminib.
Pazopanib The serum concentration of Pazopanib can be increased when it is combined with Asciminib.
Prucalopride The serum concentration of Prucalopride can be increased when it is combined with Asciminib.
Ranolazine The serum concentration of Ranolazine can be increased when it is combined with Asciminib.
Silodosin The excretion of Silodosin can be decreased when combined with Asciminib.
Topotecan The serum concentration of Topotecan can be increased when it is combined with Asciminib.
Everolimus The serum concentration of Everolimus can be increased when it is combined with Asciminib.
Rifaximin The serum concentration of Rifaximin can be increased when it is combined with Asciminib.
Irinotecan The risk or severity of neutropenia can be increased when Asciminib is combined with Irinotecan.
Vincristine The serum concentration of Vincristine can be increased when it is combined with Asciminib.
Doxorubicin The serum concentration of Doxorubicin can be increased when it is combined with Asciminib.
Phenytoin The serum concentration of Phenytoin can be increased when it is combined with Asciminib.
Pentobarbital The metabolism of Asciminib can be increased when combined with Pentobarbital.
Carbamazepine The serum concentration of Carbamazepine can be increased when it is combined with Asciminib.
Mitotane The metabolism of Asciminib can be increased when combined with Mitotane.
Primidone The metabolism of Asciminib can be increased when combined with Primidone.
Rifampin The metabolism of Asciminib can be increased when combined with Rifampicin.
Phenobarbital The serum concentration of Phenobarbital can be increased when it is combined with Asciminib.
Rifapentine The metabolism of Asciminib can be increased when combined with Rifapentine.
Dexamethasone The metabolism of Asciminib can be increased when combined with Dexamethasone.
Fosphenytoin The serum concentration of Fosphenytoin can be increased when it is combined with Asciminib.
St. John's Wort The metabolism of Asciminib can be increased when combined with St. John's Wort.
Midostaurin The serum concentration of Asciminib can be increased when it is combined with Midostaurin.
Enzalutamide The serum concentration of Asciminib can be decreased when it is combined with Enzalutamide.
Lumacaftor The metabolism of Asciminib can be increased when combined with Lumacaftor.
Apalutamide The serum concentration of Asciminib can be decreased when it is combined with Apalutamide.
Cyclosporine The serum concentration of Cyclosporine can be increased when it is combined with Asciminib.
Fluvoxamine The metabolism of Asciminib can be decreased when combined with Fluvoxamine.
Fluconazole The metabolism of Asciminib can be decreased when combined with Fluconazole.
Erythromycin The serum concentration of Asciminib can be increased when it is combined with Erythromycin.
Ziprasidone The metabolism of Asciminib can be decreased when combined with Ziprasidone.
Isradipine The metabolism of Asciminib can be decreased when combined with Isradipine.
Diltiazem The metabolism of Asciminib can be decreased when combined with Diltiazem.
Clozapine The metabolism of Asciminib can be decreased when combined with Clozapine.
Haloperidol The serum concentration of Haloperidol can be increased when it is combined with Asciminib.
Ciprofloxacin The metabolism of Asciminib can be decreased when combined with Ciprofloxacin.
Voriconazole The serum concentration of Asciminib can be increased when it is combined with Voriconazole.
Nicardipine The metabolism of Asciminib can be decreased when combined with Nicardipine.
Verapamil The serum concentration of Verapamil can be increased when it is combined with Asciminib.
Aprepitant The metabolism of Asciminib can be decreased when combined with Aprepitant.
Isoniazid The metabolism of Asciminib can be decreased when combined with Isoniazid.
Primaquine The metabolism of Asciminib can be decreased when combined with Primaquine.
Miconazole The metabolism of Asciminib can be decreased when combined with Miconazole.
Danazol The serum concentration of Asciminib can be increased when it is combined with Danazol.
Fusidic acid The metabolism of Asciminib can be decreased when combined with Fusidic acid.
Zimelidine The metabolism of Asciminib can be decreased when combined with Zimelidine.
Dronedarone The serum concentration of Dronedarone can be increased when it is combined with Asciminib.
Milnacipran The metabolism of Asciminib can be decreased when combined with Milnacipran.
Simeprevir The serum concentration of Simeprevir can be increased when it is combined with Asciminib.
Isavuconazonium The metabolism of Asciminib can be decreased when combined with Isavuconazonium.
Desvenlafaxine The metabolism of Asciminib can be decreased when combined with Desvenlafaxine.
Nilvadipine The metabolism of Asciminib can be decreased when combined with Nilvadipine.
Seproxetine The metabolism of Asciminib can be decreased when combined with Seproxetine.
Crizotinib The serum concentration of Crizotinib can be increased when it is combined with Asciminib.
Linagliptin The serum concentration of Linagliptin can be increased when it is combined with Asciminib.
Indalpine The metabolism of Asciminib can be decreased when combined with Indalpine.
Netupitant The metabolism of Asciminib can be decreased when combined with Netupitant.
Barnidipine The metabolism of Asciminib can be decreased when combined with Barnidipine.
Benidipine The metabolism of Asciminib can be decreased when combined with Benidipine.
Venetoclax The serum concentration of Venetoclax can be increased when it is combined with Asciminib.
Isavuconazole The metabolism of Asciminib can be decreased when combined with Isavuconazole.
Fosnetupitant The metabolism of Asciminib can be decreased when combined with Fosnetupitant.
Berotralstat The serum concentration of Berotralstat can be increased when it is combined with Asciminib.
Nelfinavir The serum concentration of Asciminib can be increased when it is combined with Nelfinavir.
Indinavir The serum concentration of Asciminib can be increased when it is combined with Indinavir.
Terfenadine The serum concentration of Asciminib can be increased when it is combined with Terfenadine.
Ritonavir The serum concentration of Asciminib can be increased when it is combined with Ritonavir.
Efavirenz The serum concentration of Asciminib can be increased when it is combined with Efavirenz.
Ergotamine The serum concentration of Asciminib can be increased when it is combined with Ergotamine.
Amprenavir The serum concentration of Asciminib can be increased when it is combined with Amprenavir.
Delavirdine The serum concentration of Asciminib can be increased when it is combined with Delavirdine.
Methimazole The serum concentration of Asciminib can be increased when it is combined with Methimazole.
Loperamide The serum concentration of Loperamide can be increased when it is combined with Asciminib.
Conivaptan The serum concentration of Asciminib can be increased when it is combined with Conivaptan.
Tipranavir The serum concentration of Asciminib can be increased when it is combined with Tipranavir.
Telithromycin The serum concentration of Asciminib can be increased when it is combined with Telithromycin.
Ketoconazole The serum concentration of Asciminib can be increased when it is combined with Ketoconazole.
Atazanavir The serum concentration of Asciminib can be increased when it is combined with Atazanavir.
Amiodarone The serum concentration of Asciminib can be increased when it is combined with Amiodarone.
Nefazodone The serum concentration of Asciminib can be increased when it is combined with Nefazodone.
Itraconazole The serum concentration of Asciminib can be decreased when it is combined with Itraconazole.
Naloxone The metabolism of Naloxone can be decreased when combined with Asciminib.
Clarithromycin The serum concentration of Asciminib can be increased when it is combined with Clarithromycin.
Saquinavir The serum concentration of Asciminib can be increased when it is combined with Saquinavir.
Posaconazole The serum concentration of Asciminib can be increased when it is combined with Posaconazole.
Darunavir The serum concentration of Asciminib can be increased when it is combined with Darunavir.
Lopinavir The serum concentration of Asciminib can be increased when it is combined with Lopinavir.
Ditiocarb The serum concentration of Asciminib can be increased when it is combined with Ditiocarb.
Nilotinib The serum concentration of Asciminib can be increased when it is combined with Nilotinib.
Telaprevir The serum concentration of Asciminib can be increased when it is combined with Telaprevir.
Lonafarnib The serum concentration of Asciminib can be increased when it is combined with Lonafarnib.
Boceprevir The serum concentration of Asciminib can be increased when it is combined with Boceprevir.
Elvitegravir The serum concentration of Asciminib can be increased when it is combined with Elvitegravir.
Stiripentol The serum concentration of Asciminib can be increased when it is combined with Stiripentol.

Target Protein

Tyrosine-protein kinase ABL1 ABL1

Referensi & Sumber

Synthesis reference: Schoepfer J, Jahnke W, Berellini G, Buonamici S, Cotesta S, Cowan-Jacob SW, Dodd S, Drueckes P, Fabbro D, Gabriel T, Groell JM, Grotzfeld RM, Hassan AQ, Henry C, Iyer V, Jones D, Lombardo F, Loo A, Manley PW, Pelle X, Rummel G, Salem B, Warmuth M, Wylie AA, Zoller T, Marzinzik AL, Furet P: Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1. J Med Chem. 2018 Sep 27;61(18):8120-8135. doi: 10.1021/acs.jmedchem.8b01040. Epub 2018 Sep 7. PubMed:30137981
Artikel (PubMed)
  • PMID: 30137981
    Schoepfer J, Jahnke W, Berellini G, Buonamici S, Cotesta S, Cowan-Jacob SW, Dodd S, Drueckes P, Fabbro D, Gabriel T, Groell JM, Grotzfeld RM, Hassan AQ, Henry C, Iyer V, Jones D, Lombardo F, Loo A, Manley PW, Pelle X, Rummel G, Salem B, Warmuth M, Wylie AA, Zoller T, Marzinzik AL, Furet P: Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1. J Med Chem. 2018 Sep 27;61(18):8120-8135. doi: 10.1021/acs.jmedchem.8b01040. Epub 2018 Sep 7.
  • PMID: 31006307
    Tran P, Hanna I, Eggimann FK, Schoepfer J, Ray T, Zhu B, Wang L, Priess P, Tian X, Hourcade-Potelleret F, Einolf HJ: Disposition of asciminib, a potent BCR-ABL1 tyrosine kinase inhibitor, in healthy male subjects. Xenobiotica. 2020 Feb;50(2):150-169. doi: 10.1080/00498254.2019.1594449. Epub 2019 May 6.
  • PMID: 33879198
    Hou JZ, Ye JC, Pu JJ, Liu H, Ding W, Zheng H, Liu D: Novel agents and regimens for hematological malignancies: recent updates from 2020 ASH annual meeting. J Hematol Oncol. 2021 Apr 21;14(1):66. doi: 10.1186/s13045-021-01077-3.
  • PMID: 32606014
    Jones JK, Thompson EM: Allosteric Inhibition of ABL Kinases: Therapeutic Potential in Cancer. Mol Cancer Ther. 2020 Sep;19(9):1763-1769. doi: 10.1158/1535-7163.MCT-20-0069. Epub 2020 Jun 30.
  • PMID: 26729027
    Khatri A, Wang J, Pendergast AM: Multifunctional Abl kinases in health and disease. J Cell Sci. 2016 Jan 1;129(1):9-16. doi: 10.1242/jcs.175521.

Contoh Produk & Brand

Produk: 10 • International brands: 1
Produk
  • Scemblix
    Tablet, film coated • 100 mg/1 • Oral • US • Approved
  • Scemblix
    Tablet, film coated • 20 mg/1 • Oral • US • Approved
  • Scemblix
    Tablet, film coated • 40 mg/1 • Oral • US • Approved
  • Scemblix
    Tablet, film coated • 40 mg • Oral • EU • Approved
  • Scemblix
    Tablet • 20 mg • Oral • Canada • Approved
  • Scemblix
    Tablet • 40 mg • Oral • Canada • Approved
  • Scemblix
    Tablet, film coated • 20 mg • Oral • EU • Approved
  • Scemblix
    Tablet, film coated • 20 mg • Oral • EU • Approved
Menampilkan 8 dari 10 produk.
International Brands
  • Scemblix — Novartis AG

Sekuens Gen/Protein (FASTA)

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