Binimetinib

Bezeichnung:Binimetinib

CAS-Nr606143-89-9

Englisch Name:Binimetinib

CBNumberCB82604200

SummenformelC17H15BrF2N4O3

Molgewicht441.23

MOL-Datei606143-89-9.mol

Binimetinib physikalisch-chemischer Eigenschaften

Schmelzpunkt	>203oC (dec.)
Dichte	1.67
storage temp.	-20°C
Löslichkeit	Soluble in DMSO (up to at least 25 mg/ml)
pka	14.20±0.10(Predicted)
Aggregatzustand	solid
Farbe	White
Stabilität	Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.

Sicherheit

HS Code

2933998090

Gefahreninformationscode (GHS)

Binimetinib Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Binimetinib (606143-89-9) is a potent (IC50?= 12 nM) and selective allosteric inhibitor of MEK1/2.1,2?Recently approved by the FDA for treatment of melanoma in combination with Encorafenib. Binimetinib has had limited success as monotherapy but has shown promise in combination with other chemotherapeutic agents.3-5
Verwenden
MEK 162 is a MEK1/2 inhibitor allowing it to be a effective anti-cancer medication.
Definition
ChEBI: Binimetinib is 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-fluorophenyl)nitrilo, and N-(2-hydroxyethoxy)aminocarbonyl groups, respectively. It is a MEK1 and MEK2 inhibitor (IC50= 12 nM). Approved by the FDA for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation in combination with encorafenib. It has a role as an EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor, an antineoplastic agent and an apoptosis inducer. It is a member of benzimidazoles, a member of bromobenzenes, a member of monofluorobenzenes, a hydroxamic acid ester and a secondary amino compound.
Trademarks
Mektovi
Allgemeine Beschreibung
Class: dual threonine/tyrosine kinase; Treatment: melanoma with BRAF mutations; Other name: ARRY-162; Oral bioavailability = 50%; Elimination half-life = 3.5 h; Protein binding = 97%
Pharmakokinetik
After oral administration, binimetinib is absorbed rapidly, with a median tmax of 1.48 h. Binimetinib is 50% orally bioavailable and exhibits a short elimination half-life of 3.5 h. Consequently, it requires twice-daily dosing regimen. Binimetinib undergoes UGT1A1-mediated glucuronidation, which contributes up to 61% of the overall metabolism. Other metabolic pathways include N-dealkylation, amide hydrolysis, and loss of ethanediol from the side chain.
target
Primary target: MEK1/2
Einzelnachweise
1) Lee?et al.?(2010),?Preclinical development of ARRY-162, a potent and selective MEK1/2 inhibitor;?Cancer Res.?70?2515 2) Winski?et al.?(2010),?MEK162 (ARRY-162), a novel MEK ? inhibitor, inhibits tumor growth regardless of KRAS/RAF pathway mutations;?EJC Supplements?8?56 3) Lee?et al.?(2016),?Efficacy of the combination of MEK and CDK4/6 inhibitors in vitro and in vivo in KRAS mutant colorectal cancer models;?Oncotarget?7?39595 4) Gong?et al.?(2017),?MEK162 Enhances Antitumor Activity of 5-Fluorouracil and Trifluridine in KRAS-mutated Human Colorectal Cancer Cell Lines;?Anticancer Res.?37?2831 5) Van Cutsem?et al.?(2019),?Binimetinib, Encorafenib, and Cetuximab Triplet Therapy for Patients With BRAF V600E-Mutant Metastatic Colorectal Cancer: Safety Lead-In Results From Phase III BEACON Colorectal Cancer study;?J. Clin. Oncol.?180?2459

Binimetinib Upstream-Materialien And Downstream Produkte

Binimetinib Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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