Peringatan Keamanan

Toxicity information regarding selpercatinib is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as hepatotoxicity, hypertension, prolonged QT interval, and hemorrhaging. Symptomatic and supportive measures are recommended.L13604

Selpercatinib

DB15685

small molecule approved investigational

Deskripsi

Selpercatinib is a kinase inhibitor with enhanced specificity for RET tyrosine kinase receptors (RTKs) over other RTK classes.A202055, A202052, L13604 Enhanced RET (Rearranged during transfection) oncogene expression is a hallmark of many cancers. Although multikinase inhibitors, including cabozantinib, ponatinib, sorafenib, sunitinib, and vandetanib, have shown efficacy in RET-driven cancers, their lack of specificity is generally associated with substantial toxicity. Selpercatinib (LOXO-292) and pralsetinib (BLU-667) represent the first generation of specific RET RTK inhibitors for the treatment of RET-driven cancers.A202049, A202055, A202052, L13604

Although selpercatinib is currently still under investigation in clinical trial NCT04211337, it was granted accelerated FDA approval on May 8, 2020, for specific RET-driven cancer indications. It is currently marketed under the brand name RETEVMO™ by Loxo Oncology Inc.L13604 Selpercatinib is also approved by the European Commission.

Struktur Molekul 2D

Berat 525.613
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) Selpercatinib has a half-life of 32 hours in healthy individuals.[L13604]
Volume Distribusi Selpercatinib has an apparent volume of distribution of 191 L; the volume of distribution increases with increasing body weight.[L13604]
Klirens (Clearance) Selpercatinib has an apparent clearance of 6L/h; the clearance increases with increasing body weight.[L13604]

Absorpsi

In patients with locally advanced or metastatic solid tumours receiving 160 mg of selpercatinib twice daily, steady-state was achieved after approximately 7 days, with a Cmax of 2,980 (CV 53%) and AUC0-24h of 51,600 (CV 58%). The absolute bioavailability is between 60 and 82% (mean 73%), and the median tmax is two hours. Food has no apparent effect on the AUC or Cmax of selpercatinib. Patients with hepatic impairment display a concomitant increase in AUC0-INF for mild (7%), moderate (32%), and severe (77%) impairment.L13604

Metabolisme

Selpercatinib is predominantly metabolized in the liver by CYP3A4.L13604

Rute Eliminasi

Selpercatinib administered as a single 160 mg dose in healthy individuals was primarily recovered in feces (69%, 14% unchanged) and urine (24%, 12% unchanged).L13604

Interaksi Makanan

1 Data
  • 1. Take with or without food. Patients on proton pump inhibitors should take selpercatinib with food.

Interaksi Obat

987 Data
Valsartan Selpercatinib may decrease the antihypertensive activities of Valsartan.
Ramipril Selpercatinib may decrease the antihypertensive activities of Ramipril.
Esmolol Selpercatinib may decrease the antihypertensive activities of Esmolol.
Betaxolol Selpercatinib may decrease the antihypertensive activities of Betaxolol.
Remikiren Selpercatinib may decrease the antihypertensive activities of Remikiren.
Bethanidine Selpercatinib may decrease the antihypertensive activities of Bethanidine.
Guanadrel Selpercatinib may decrease the antihypertensive activities of Guanadrel.
Metoprolol Selpercatinib may decrease the antihypertensive activities of Metoprolol.
Olmesartan Selpercatinib may decrease the antihypertensive activities of Olmesartan.
Chlorthalidone Selpercatinib may decrease the antihypertensive activities of Chlorthalidone.
Nitroprusside Selpercatinib may decrease the antihypertensive activities of Nitroprusside.
Atenolol Selpercatinib may decrease the antihypertensive activities of Atenolol.
Minoxidil Selpercatinib may decrease the antihypertensive activities of Minoxidil.
Timolol Selpercatinib may decrease the antihypertensive activities of Timolol.
Treprostinil The serum concentration of Treprostinil can be increased when it is combined with Selpercatinib.
Amlodipine Selpercatinib may decrease the antihypertensive activities of Amlodipine.
Nimodipine Selpercatinib may decrease the antihypertensive activities of Nimodipine.
Nisoldipine Selpercatinib may decrease the antihypertensive activities of Nisoldipine.
Bendroflumethiazide Selpercatinib may decrease the antihypertensive activities of Bendroflumethiazide.
Prazosin Selpercatinib may decrease the antihypertensive activities of Prazosin.
Fosinopril Selpercatinib may decrease the antihypertensive activities of Fosinopril.
Trandolapril Selpercatinib may decrease the antihypertensive activities of Trandolapril.
Metolazone Selpercatinib may decrease the antihypertensive activities of Metolazone.
Lercanidipine Selpercatinib may decrease the antihypertensive activities of Lercanidipine.
Benazepril Selpercatinib may decrease the antihypertensive activities of Benazepril.
Propranolol Selpercatinib may decrease the antihypertensive activities of Propranolol.
Clonidine Selpercatinib may decrease the antihypertensive activities of Clonidine.
Enalapril Selpercatinib may decrease the antihypertensive activities of Enalapril.
Doxazosin Selpercatinib may decrease the antihypertensive activities of Doxazosin.
Labetalol Selpercatinib may decrease the antihypertensive activities of Labetalol.
Cyclothiazide Selpercatinib may decrease the antihypertensive activities of Cyclothiazide.
Bisoprolol Selpercatinib may decrease the antihypertensive activities of Bisoprolol.
Candoxatril Selpercatinib may decrease the antihypertensive activities of Candoxatril.
Guanabenz Selpercatinib may decrease the antihypertensive activities of Guanabenz.
Mecamylamine Selpercatinib may decrease the antihypertensive activities of Mecamylamine.
Losartan Selpercatinib may decrease the antihypertensive activities of Losartan.
Moexipril Selpercatinib may decrease the antihypertensive activities of Moexipril.
Phentolamine Selpercatinib may decrease the antihypertensive activities of Phentolamine.
Furosemide Selpercatinib may decrease the antihypertensive activities of Furosemide.
Eplerenone Selpercatinib may decrease the antihypertensive activities of Eplerenone.
Lisinopril Selpercatinib may decrease the antihypertensive activities of Lisinopril.
Nitroglycerin Selpercatinib may decrease the antihypertensive activities of Nitroglycerin.
Metyrosine Selpercatinib may decrease the antihypertensive activities of Metyrosine.
Hydroflumethiazide Selpercatinib may decrease the antihypertensive activities of Hydroflumethiazide.
Cryptenamine Selpercatinib may decrease the antihypertensive activities of Cryptenamine.
Perindopril Selpercatinib may decrease the antihypertensive activities of Perindopril.
Candesartan cilexetil Selpercatinib may decrease the antihypertensive activities of Candesartan cilexetil.
Tolazoline Selpercatinib may decrease the antihypertensive activities of Tolazoline.
Fenoldopam Selpercatinib may decrease the antihypertensive activities of Fenoldopam.
Indapamide Selpercatinib may decrease the antihypertensive activities of Indapamide.
Tadalafil Selpercatinib may decrease the antihypertensive activities of Tadalafil.
Alprenolol Selpercatinib may decrease the antihypertensive activities of Alprenolol.
Eprosartan Selpercatinib may decrease the antihypertensive activities of Eprosartan.
Chlorothiazide Selpercatinib may decrease the antihypertensive activities of Chlorothiazide.
Quinapril Selpercatinib may decrease the antihypertensive activities of Quinapril.
Omapatrilat Selpercatinib may decrease the antihypertensive activities of Omapatrilat.
Phenoxybenzamine Selpercatinib may decrease the antihypertensive activities of Phenoxybenzamine.
Pindolol Selpercatinib may decrease the antihypertensive activities of Pindolol.
Telmisartan Selpercatinib may decrease the antihypertensive activities of Telmisartan.
Methyldopa Selpercatinib may decrease the antihypertensive activities of Methyldopa.
Hydrochlorothiazide Selpercatinib may decrease the antihypertensive activities of Hydrochlorothiazide.
Guanfacine Selpercatinib may decrease the antihypertensive activities of Guanfacine.
Trichlormethiazide Selpercatinib may decrease the antihypertensive activities of Trichlormethiazide.
Felodipine Selpercatinib may decrease the antihypertensive activities of Felodipine.
Nitrendipine Selpercatinib may decrease the antihypertensive activities of Nitrendipine.
Deserpidine Selpercatinib may decrease the antihypertensive activities of Deserpidine.
Pentolinium Selpercatinib may decrease the antihypertensive activities of Pentolinium.
Trimethaphan Selpercatinib may decrease the antihypertensive activities of Trimethaphan.
Diazoxide Selpercatinib may decrease the antihypertensive activities of Diazoxide.
Carvedilol Selpercatinib may decrease the antihypertensive activities of Carvedilol.
Bretylium Selpercatinib may decrease the antihypertensive activities of Bretylium.
Terazosin Selpercatinib may decrease the antihypertensive activities of Terazosin.
Guanethidine Selpercatinib may decrease the antihypertensive activities of Guanethidine.
Rescinnamine Selpercatinib may decrease the antihypertensive activities of Rescinnamine.
Acebutolol Selpercatinib may decrease the antihypertensive activities of Acebutolol.
Captopril Selpercatinib may decrease the antihypertensive activities of Captopril.
Epoprostenol Selpercatinib may decrease the antihypertensive activities of Epoprostenol.
Bepridil Selpercatinib may decrease the antihypertensive activities of Bepridil.
Hydralazine Selpercatinib may decrease the antihypertensive activities of Hydralazine.
Bevantolol Selpercatinib may decrease the antihypertensive activities of Bevantolol.
Practolol Selpercatinib may decrease the antihypertensive activities of Practolol.
Polythiazide Selpercatinib may decrease the antihypertensive activities of Polythiazide.
Cilazapril Selpercatinib may decrease the antihypertensive activities of Cilazapril.
Saprisartan Selpercatinib may decrease the antihypertensive activities of Saprisartan.
Spirapril Selpercatinib may decrease the antihypertensive activities of Spirapril.
Penbutolol Selpercatinib may decrease the antihypertensive activities of Penbutolol.
Mibefradil Selpercatinib may decrease the antihypertensive activities of Mibefradil.
Oxprenolol Selpercatinib may decrease the antihypertensive activities of Oxprenolol.
Pargyline Selpercatinib may decrease the antihypertensive activities of Pargyline.
Dexpropranolol Selpercatinib may decrease the antihypertensive activities of Dexpropranolol.
Tienilic acid Selpercatinib may decrease the antihypertensive activities of Tienilic acid.
Debrisoquine Selpercatinib may decrease the antihypertensive activities of Debrisoquine.
Celiprolol Selpercatinib may decrease the antihypertensive activities of Celiprolol.
Nebivolol Selpercatinib may decrease the antihypertensive activities of Nebivolol.
Lofexidine Selpercatinib may decrease the antihypertensive activities of Lofexidine.
Sitaxentan Selpercatinib may decrease the antihypertensive activities of Sitaxentan.
Ambrisentan Selpercatinib may decrease the antihypertensive activities of Ambrisentan.
Diethylnorspermine Selpercatinib may decrease the antihypertensive activities of Diethylnorspermine.
Pinacidil Selpercatinib may decrease the antihypertensive activities of Pinacidil.
Bupranolol Selpercatinib may decrease the antihypertensive activities of Bupranolol.

Target Protein

Proto-oncogene tyrosine-protein kinase receptor Ret RET
Vascular endothelial growth factor receptor 1 FLT1
Vascular endothelial growth factor receptor 3 FLT4
Fibroblast growth factor receptor 1 FGFR1
Fibroblast growth factor receptor 2 FGFR2
Fibroblast growth factor receptor 3 FGFR3

Referensi & Sumber

Synthesis reference: Charles Todd Eary, Stacey Spencer, Zack Crane, Katelyn Chando, Sylvie Asselin, Weidong Liu, Mike Welch, Adam Cook, Gabrielle R. Kolakowski, Andrew T. Metcalf, David A. Moreno, Tony P. Tang. "Process for the preparation of 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo3.1.1heptan-3-yl)pyridin-3-yl)pyrazolo1,5-apyridine-3-carbonitrile." Patent WO2019075092A1, issued April 18, 2019.
Artikel (PubMed)
  • PMID: 31715421
    Li AY, McCusker MG, Russo A, Scilla KA, Gittens A, Arensmeyer K, Mehra R, Adamo V, Rolfo C: RET fusions in solid tumors. Cancer Treat Rev. 2019 Dec;81:101911. doi: 10.1016/j.ctrv.2019.101911. Epub 2019 Oct 30.
  • PMID: 32296961
    Russo A, Lopes AR, McCusker MG, Garrigues SG, Ricciardi GR, Arensmeyer KE, Scilla KA, Mehra R, Rolfo C: New Targets in Lung Cancer (Excluding EGFR, ALK, ROS1). Curr Oncol Rep. 2020 Apr 16;22(5):48. doi: 10.1007/s11912-020-00909-8.
  • PMID: 31988000
    Solomon BJ, Tan L, Lin JJ, Wong SQ, Hollizeck S, Ebata K, Tuch BB, Yoda S, Gainor JF, Sequist LV, Oxnard GR, Gautschi O, Drilon A, Subbiah V, Khoo C, Zhu EY, Nguyen M, Henry D, Condroski KR, Kolakowski GR, Gomez E, Ballard J, Metcalf AT, Blake JF, Dawson SJ, Blosser W, Stancato LF, Brandhuber BJ, Andrews S, Robinson BG, Rothenberg SM: RET Solvent Front Mutations Mediate Acquired Resistance to Selective RET Inhibition in RET-Driven Malignancies. J Thorac Oncol. 2020 Apr;15(4):541-549. doi: 10.1016/j.jtho.2020.01.006. Epub 2020 Jan 24.
  • PMID: 32083997
    Subbiah V, Yang D, Velcheti V, Drilon A, Meric-Bernstam F: State-of-the-Art Strategies for Targeting RET-Dependent Cancers. J Clin Oncol. 2020 Apr 10;38(11):1209-1221. doi: 10.1200/JCO.19.02551. Epub 2020 Feb 21.
  • PMID: 2992805
    Takahashi M, Ritz J, Cooper GM: Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell. 1985 Sep;42(2):581-8. doi: 10.1016/0092-8674(85)90115-1.
  • PMID: 25047660
    Qian Y, Chai S, Liang Z, Wang Y, Zhou Y, Xu X, Zhang C, Zhang M, Si J, Huang F, Huang Z, Hong W, Wang K: KIF5B-RET fusion kinase promotes cell growth by multilevel activation of STAT3 in lung cancer. Mol Cancer. 2014 Jul 21;13:176. doi: 10.1186/1476-4598-13-176.

Contoh Produk & Brand

Produk: 19 • International brands: 1
Produk
  • Retevmo
    Capsule • 40 mg/1 • Oral • US • Approved
  • Retevmo
    Capsule • 80 mg/1 • Oral • US • Approved
  • Retevmo
    Tablet, coated • 40 mg/1 • Oral • US • Approved
  • Retevmo
    Tablet, coated • 80 mg/1 • Oral • US • Approved
  • Retevmo
    Tablet, coated • 120 mg/1 • Oral • US • Approved
  • Retevmo
    Tablet, coated • 160 mg/1 • Oral • US • Approved
  • Retevmo
    Capsule • 40 mg • Oral • Canada • Approved
  • Retevmo
    Capsule • 80 mg • Oral • Canada • Approved
Menampilkan 8 dari 19 produk.
International Brands
  • Retevmo — Loxo Oncology Inc.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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