Selumetinib

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Achtung

• Gefahrenhinweise

  H317：Kann allergische Hautreaktionen verursachen.

  H318：Verursacht schwere Augenschäden.

  H373：Kann die Organe schädigen bei längerer oder wiederholter Exposition.

• Sicherheit

  P262：Nicht in die Augen, auf die Haut oder auf die Kleidung gelangen lassen.

  P280：Schutzhandschuhe/Schutzkleidung/Augenschutz tragen.

  P312：Bei Unwohlsein GIFTINFORMATIONSZENTRUM/Arzt/... (geeignete Stelle für medizinische Notfallversorgung vom Hersteller/Lieferanten anzugeben) anrufen.

Selumetinib Chemische Eigenschaften,Einsatz,Produktion Methoden

• Beschreibung

  Selumetinib (AZD6244; ARRY-142886) is an oral MEK inhibitor. In a randomized trial, NSCLC patients with wild-type KRAS were randomized to erlotinib alone or combination therapy with selumetinib, while mutant KRAS patients were randomized to selumetinib alone or combination therapy. The primary end points were PFS for the KRAS wild-type cohort and objective response rate (ORR) for the KRAS mutant cohort. Results were not impressive, with no PFS difference in the KRAS wild-type arm (2.4 vs. 2.1?months) and no ORR difference in the KRASmutated subgroup (0% vs. 10%). A planned trial of selumetinib in combination with the anti-PD-L1 antibody durvalumab has since been suspended (NCT03004105).

• Verwenden

  It is a tight-binding, uncompetitive inhibitor of mitogen-activated protein kinase kinases (MEK) 1 and 2 currently in clinical development. It is useful as biomarker in human lung cancer cell. Potent MEK inhibitor.

• Definition

  ChEBI: A member of the class of benzimidazoles that is 1-methyl-1H-benzimidazole which is substituted at positions 4, 5, and 6 by fluorine, (4-bromo-2-chlorophenyl)amino, and N-(2-hydroxyethoxy)aminocarbonyl groups, respectiv ly. It is a MEK1 and MEK2 inhibitor.

• Trademarks

  Koselugo

• Allgemeine Beschreibung

  Class: dual threonine/tyrosine kinase; Treatment: children with NF1; Other name: AZD-6244, ARRY-142886; Oral bioavailability = 62%; Elimination half-life = 6.2 h; Protein binding = 97.7%

• target

  MEK1

• Stoffwechsel

  Following oral administration of radiolabeled selumetinib, the most prominent drug-related component in the plasma was selumetinib, accounting for 40% of the plasma radioactivity. The major circulating metabolite was an amide glucuronide 2, which accounted for 22% of the plasma radioactivity. This metabolite resulted from loss of the ethanediol moiety to give the primary amide 1, which underwent glucuronidation and an additional loss of 2 mass units, most likely due to further oxidation of the N-methylbenzimidazole moiety (Fig. 5).
  

• Lager

  Store at -20°C

• Dosage

  Selumetinib is characterized by a moderate oral bioavailability (62%) and a relatively short half-life (6.2 h), and these properties contribute to twice-daily dosing regimen (25 mg dosage).

• Einzelnachweise

  1) Davies?et al. (2007),?AZD6244(ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamics relationship, and potential for combination in preclinical models; Mol. Cancer Ther.,?6?2209 2) Yeh?et al. (2007),?Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor; Clin. Cancer Res.,?13?1576 3) Catalanotti?et al. (2013),?Phase II trial of MEK inhibitor selumetinib(AZD6244) in patients with BRAFV600E/K-mutated melanoma; Clin. Cancer Res.,?19?2257 4) O’Neil?et al. (2011),?Phase II study of the mitogen-activated protein kinase 1/2 inhibitor selumetinib in patients with advanced hepatocellular carcinoma; J. Clin. Oncol.,?29?2350 5) Khurum?et al. (2012),?A phase I dose escalation study of oral MK-2206 (allosteric Akt inhibitor) with oral selumetinib (AZD6244)(MEK 1/2 inhibitor) in patients with advanced or metastatic solid tumors; J. Clin. Oncol.,?30?e13599 6) Hainsworth?et al. (2010),?A phase II, open label, randomized study to assess the efficacy and safety of AZD6244 versus pemetrexed in patients with non-small cell lung cancer who have failed one or two prior chemotherapeutic regimens; J. Thorac. Oncol.,?5?1630 7) Bodoky?et al. (2012),?A phase II open-label randomized study to assess the efficacy and safety of selumetinib (AZD6244) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy; Invest. New Drugs,?30?1216

Selumetinib Upstream-Materialien And Downstream Produkte

Selumetinib Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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