Peringatan Keamanan

The oral LD50 of umbralisib in rats is 3320 mg/kg.L31898 Overdose information is not readily available on prescribing information L31878 or the literature. In any overdose, supportive and symptomatic treatment should be provided as required.

Umbralisib

DB14989

small molecule approved investigational withdrawn

Deskripsi

Marginal zone lymphoma is a rare, slowly progressing type of non-Hodgkin lymphoma initially treated with rituximab (an anti-CD20 drug), either alone or in combination with chemotherapy. Unfortunately, many patients experience a relapse or develop resistance to these drugs. Treatment options then become limited, and alternate treatments for the lymphoma are required to control disease progression.A229363 Follicular lymphoma is also treated with rituximab and other chemotherapeutic agents, but may show similar progression.A229668

On February 5, 2021, the Food and Drug Administration granted accelerated approval to umbralisib, a kinase inhibitor for PI3K-delta and casein kinase CK1-epsilon, based on promising results from clinical trials. It was marketed as Ukoniq by TG Therapeutics and has been approved for the treatment of relapsing and refractory marginal cell lymphoma and follicular lymphoma in adults.L31863 Umbralisib inhibits casein kinase, a primary regulator of protein translation, kinase-1?, distinguishing it from other lymphoma treatments. While it initially offered a promising therapy for patients experiencing relapsing or refractory disease,A229363 umbralisib was withdrawn from the market due to safety concerns as the drug was associated with a possible increased risk of death outweighing the benefits.L41930

Struktur Molekul 2D

Berat 571.56
Wujud solid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The effective half-life of Umbralisib is about 91 hours.[L31878]
Volume Distribusi The average apparent central volume of distribution of umbralisib is 312 L.[L31878]
Klirens (Clearance) The average apparent clearance of umbralisib is 15.5 L/h.[L31878]

Absorpsi

Umbralisib is rapidly absorbed in the GI tract.A229363 The Tmax of umbralisib is about 4 hours. After consumption of a high-fat, high calorie meal with umbralisib, the AUC increased by 61% and the Cmax increased by 115%.L31878

Metabolisme

During in vitro studies, umbralisib was metabolized by CYP2C9, CYP3A4, and CYP1A2 enzymes.L31878

Rute Eliminasi

During pharmacokinetic studies, about 81% of the umbralisib dose was recovered in feces (17% unchanged). Approximately 3% was detected in the urine (0.02% unchanged) after a radiolabeled dose of 800 mg in healthy volunteers.L31878

Interaksi Makanan

1 Data
  • 1. Take with food. Food increases the bioavailability and concentration of umbralisib.

Interaksi Obat

198 Data
Afatinib The serum concentration of Afatinib can be increased when it is combined with Umbralisib.
Bosutinib The serum concentration of Bosutinib can be increased when it is combined with Umbralisib.
Brentuximab vedotin The serum concentration of Brentuximab vedotin can be increased when it is combined with Umbralisib.
Colchicine The serum concentration of Colchicine can be increased when it is combined with Umbralisib.
Edoxaban The serum concentration of Edoxaban can be increased when it is combined with Umbralisib.
Ledipasvir The serum concentration of Ledipasvir can be increased when it is combined with Umbralisib.
Naloxegol The serum concentration of Naloxegol can be increased when it is combined with Umbralisib.
Pazopanib The serum concentration of Pazopanib can be increased when it is combined with Umbralisib.
Prucalopride The serum concentration of Prucalopride can be increased when it is combined with Umbralisib.
Ranolazine The serum concentration of Ranolazine can be increased when it is combined with Umbralisib.
Silodosin The excretion of Silodosin can be decreased when combined with Umbralisib.
Topotecan The serum concentration of Topotecan can be increased when it is combined with Umbralisib.
Everolimus The serum concentration of Everolimus can be increased when it is combined with Umbralisib.
Rifaximin The serum concentration of Rifaximin can be increased when it is combined with Umbralisib.
Vincristine The excretion of Vincristine can be decreased when combined with Umbralisib.
Doxorubicin The serum concentration of Doxorubicin can be increased when it is combined with Umbralisib.
Betrixaban The serum concentration of Betrixaban can be increased when it is combined with Umbralisib.
Pravastatin The serum concentration of Pravastatin can be increased when it is combined with Umbralisib.
Sildenafil The serum concentration of Sildenafil can be increased when it is combined with Umbralisib.
Morphine The serum concentration of Morphine can be increased when it is combined with Umbralisib.
Tenofovir disoproxil The serum concentration of Tenofovir disoproxil can be increased when it is combined with Umbralisib.
Clobazam The serum concentration of Clobazam can be increased when it is combined with Umbralisib.
Mefloquine The serum concentration of Mefloquine can be increased when it is combined with Umbralisib.
Quinine The serum concentration of Quinine can be increased when it is combined with Umbralisib.
Toremifene The serum concentration of Toremifene can be increased when it is combined with Umbralisib.
Bisoprolol The serum concentration of Bisoprolol can be increased when it is combined with Umbralisib.
Simvastatin The serum concentration of Simvastatin can be increased when it is combined with Umbralisib.
Mannitol The serum concentration of Mannitol can be increased when it is combined with Umbralisib.
Loperamide The excretion of Loperamide can be decreased when combined with Umbralisib.
Vardenafil The serum concentration of Vardenafil can be increased when it is combined with Umbralisib.
Clomifene The serum concentration of Clomifene can be increased when it is combined with Umbralisib.
Tipranavir The serum concentration of Tipranavir can be increased when it is combined with Umbralisib.
Fexofenadine The serum concentration of Fexofenadine can be increased when it is combined with Umbralisib.
Tegaserod The serum concentration of Tegaserod can be increased when it is combined with Umbralisib.
Saquinavir The serum concentration of Saquinavir can be increased when it is combined with Umbralisib.
Sitagliptin The serum concentration of Sitagliptin can be increased when it is combined with Umbralisib.
Posaconazole The serum concentration of Posaconazole can be increased when it is combined with Umbralisib.
Darunavir The serum concentration of Darunavir can be increased when it is combined with Umbralisib.
Paliperidone The serum concentration of Paliperidone can be increased when it is combined with Umbralisib.
Mibefradil The serum concentration of Mibefradil can be increased when it is combined with Umbralisib.
Belinostat The serum concentration of Belinostat can be increased when it is combined with Umbralisib.
Indacaterol The serum concentration of Indacaterol can be increased when it is combined with Umbralisib.
Telaprevir The serum concentration of Telaprevir can be increased when it is combined with Umbralisib.
Rivaroxaban The serum concentration of Rivaroxaban can be increased when it is combined with Umbralisib.
Simeprevir The serum concentration of Simeprevir can be increased when it is combined with Umbralisib.
Ambrisentan The serum concentration of Ambrisentan can be increased when it is combined with Umbralisib.
Cethromycin The serum concentration of Cethromycin can be increased when it is combined with Umbralisib.
Apixaban The serum concentration of Apixaban can be increased when it is combined with Umbralisib.
Odanacatib The serum concentration of Odanacatib can be increased when it is combined with Umbralisib.
Ticagrelor The serum concentration of Ticagrelor can be increased when it is combined with Umbralisib.
Linagliptin The serum concentration of Linagliptin can be increased when it is combined with Umbralisib.
Mirabegron The serum concentration of Mirabegron can be increased when it is combined with Umbralisib.
Canagliflozin The serum concentration of Canagliflozin can be increased when it is combined with Umbralisib.
Dolutegravir The serum concentration of Dolutegravir can be increased when it is combined with Umbralisib.
Sofosbuvir The serum concentration of Sofosbuvir can be increased when it is combined with Umbralisib.
Idelalisib The serum concentration of Idelalisib can be increased when it is combined with Umbralisib.
Umeclidinium The serum concentration of Umeclidinium can be increased when it is combined with Umbralisib.
Lenvatinib The serum concentration of Lenvatinib can be increased when it is combined with Umbralisib.
Nintedanib The serum concentration of Nintedanib can be increased when it is combined with Umbralisib.
Technetium Tc-99m sestamibi The serum concentration of Technetium Tc-99m sestamibi can be increased when it is combined with Umbralisib.
Dasabuvir The serum concentration of Dasabuvir can be increased when it is combined with Umbralisib.
Methylene blue The serum concentration of Methylene blue can be increased when it is combined with Umbralisib.
Ombitasvir The serum concentration of Ombitasvir can be increased when it is combined with Umbralisib.
Paritaprevir The serum concentration of Paritaprevir can be increased when it is combined with Umbralisib.
Selexipag The serum concentration of Selexipag can be increased when it is combined with Umbralisib.
Elbasvir The serum concentration of Elbasvir can be increased when it is combined with Umbralisib.
Grazoprevir The serum concentration of Grazoprevir can be increased when it is combined with Umbralisib.
Velpatasvir The serum concentration of Velpatasvir can be increased when it is combined with Umbralisib.
Tucatinib The serum concentration of Tucatinib can be increased when it is combined with Umbralisib.
Selumetinib The serum concentration of Selumetinib can be increased when it is combined with Umbralisib.
Voclosporin The serum concentration of Voclosporin can be increased when it is combined with Umbralisib.
Tezacaftor The serum concentration of Tezacaftor can be increased when it is combined with Umbralisib.
Lasmiditan The serum concentration of Lasmiditan can be increased when it is combined with Umbralisib.
Talinolol The serum concentration of Talinolol can be increased when it is combined with Umbralisib.
Fostemsavir The serum concentration of Fostemsavir can be increased when it is combined with Umbralisib.
Revefenacin The serum concentration of Revefenacin can be increased when it is combined with Umbralisib.
Valspodar The serum concentration of Valspodar can be increased when it is combined with Umbralisib.
Lemborexant The serum concentration of Lemborexant can be increased when it is combined with Umbralisib.
Duvelisib The serum concentration of Duvelisib can be increased when it is combined with Umbralisib.
Glasdegib The serum concentration of Glasdegib can be increased when it is combined with Umbralisib.
Elagolix The serum concentration of Elagolix can be increased when it is combined with Umbralisib.
Voxilaprevir The serum concentration of Voxilaprevir can be increased when it is combined with Umbralisib.
Gilteritinib The serum concentration of Gilteritinib can be increased when it is combined with Umbralisib.
Omadacycline The serum concentration of Omadacycline can be increased when it is combined with Umbralisib.
Fedratinib The serum concentration of Fedratinib can be increased when it is combined with Umbralisib.
Grapiprant The serum concentration of Grapiprant can be increased when it is combined with Umbralisib.
Tazemetostat The serum concentration of Tazemetostat can be increased when it is combined with Umbralisib.
Darolutamide The serum concentration of Darolutamide can be increased when it is combined with Umbralisib.
Enfortumab vedotin The serum concentration of Enfortumab vedotin can be increased when it is combined with Umbralisib.
Lusutrombopag The serum concentration of Lusutrombopag can be increased when it is combined with Umbralisib.
Pibrentasvir The serum concentration of Pibrentasvir can be increased when it is combined with Umbralisib.
Glecaprevir The serum concentration of Glecaprevir can be increased when it is combined with Umbralisib.
Tenofovir The serum concentration of Tenofovir can be increased when it is combined with Umbralisib.
Prednisolone phosphate The serum concentration of Prednisolone phosphate can be increased when it is combined with Umbralisib.
Ripretinib The serum concentration of Ripretinib can be increased when it is combined with Umbralisib.
Belantamab mafodotin The serum concentration of Belantamab mafodotin can be increased when it is combined with Umbralisib.
Trilaciclib The serum concentration of Trilaciclib can be increased when it is combined with Umbralisib.
Daptomycin The serum concentration of Daptomycin can be increased when it is combined with Umbralisib.
Avanafil The serum concentration of Avanafil can be increased when it is combined with Umbralisib.
Tivozanib The serum concentration of Tivozanib can be increased when it is combined with Umbralisib.

Target Protein

Casein kinase I isoform epsilon CSNK1E
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform PIK3CD
Tyrosine-protein kinase ABL1 ABL1

Referensi & Sumber

Artikel (PubMed)
  • PMID: 29475723
    Burris HA 3rd, Flinn IW, Patel MR, Fenske TS, Deng C, Brander DM, Gutierrez M, Essell JH, Kuhn JG, Miskin HP, Sportelli P, Weiss MS, Vakkalanka S, Savona MR, O'Connor OA: Umbralisib, a novel PI3Kdelta and casein kinase-1epsilon inhibitor, in relapsed or refractory chronic lymphocytic leukaemia and lymphoma: an open-label, phase 1, dose-escalation, first-in-human study. Lancet Oncol. 2018 Apr;19(4):486-496. doi: 10.1016/S1470-2045(18)30082-2. Epub 2018 Feb 20.
  • PMID: 30936084
    Authors unspecified: Umbralisib: Treatment for a Rare Lymphoma? Cancer Discov. 2019 Jun;9(6):OF5. doi: 10.1158/2159-8290.CD-NB2019-045. Epub 2019 Apr 1.
  • PMID: 31558467
    Lunning M, Vose J, Nastoupil L, Fowler N, Burger JA, Wierda WG, Schreeder MT, Siddiqi T, Flowers CR, Cohen JB, Sportelli P, Miskin HP, Weiss MS, O'Brien S: Ublituximab and umbralisib in relapsed/refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood. 2019 Nov 21;134(21):1811-1820. doi: 10.1182/blood.2019002118.
  • PMID: 25024054
    Curran E, Smith SM: Phosphoinositide 3-kinase inhibitors in lymphoma. Curr Opin Oncol. 2014 Sep;26(5):469-75. doi: 10.1097/CCO.0000000000000113.
  • PMID: 31814159
    Freedman A, Jacobsen E: Follicular lymphoma: 2020 update on diagnosis and management. Am J Hematol. 2020 Mar;95(3):316-327. doi: 10.1002/ajh.25696. Epub 2019 Dec 22.

Contoh Produk & Brand

Produk: 1 • International brands: 1
Produk
  • Ukoniq
    Tablet, film coated • 260.2 mg/1 • Oral • US • Approved
International Brands
  • UKONIQ — Rhizen Pharmaceuticals AG

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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