606143-52-6

Basic information

• Product Name: Selumetinib
• Synonyms: ARRY 142886;AZD 6244;5-[(4-Bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide;Selumetinib;5-(4-Bromo-2-chlorophenylamino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzo[d]imidazole-6-carboxamide;6-(4-Bromo-2-chlorophenylamino)-7-fluoro-N-(2-hydroxyethoxy)-3-methyl-3H-benzo[d]imidazole-5-carboxamide;SeluMatinib(5-[(4-BroMo-2-chlorophenyl)aMino]-4-fluoro-N-(2-hydroxyethoxy)-1-Methyl-1H-benziMidazole-6-carboxaMide;AZD6244(SeluMetinib)
• CAS NO: 606143-52-6
• Molecular Formula: C₁₇H₁₅BrClFN₄O₃
• Molecular Weight: 457.685
• Product Categories: API;Aromatics;Heterocycles;Inhibitor;Intermediates & Fine Chemicals;Pharmaceuticals;apis;Antineoplastic;Inhibitors;MAPK
• Mol File: 606143-52-6.mol
• Article Data: 6

Chemical Properties

• Appearance: /
• Density: 1.69
• Storage Temp.: -20°
• Solubility: Soluble in DMSO (up to 50 mg/ml) or in Ethanol (up to 2 mg/ml)
• PKA: 14.20±0.10(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 2 months.
• CAS DataBase Reference: Selumetinib(CAS DataBase Reference)
• NIST Chemistry Reference: Selumetinib(606143-52-6)
• EPA Substance Registry System: Selumetinib(606143-52-6)

Safety Data

• Hazardous Substances Data: 606143-52-6(Hazardous Substances Data)

Usage

Indications and Usage

Selumetinib, 1 has a chemical name of 5-[(4-Bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide. It was developed by British company AstraZeneca and is used to treat advanced non-small cell lung cancer (NSCLC). It is mainly used to treat bile duct cancer, colon cancer, NSCLC, etc. Currently, Selumetinib is in stage III clinical trials for treatment of NSCLC.

Mechanisms of Action

Selumetinib is the first mitogenextracellular kinase (MEK1/2) inhibitor to be used in thyroid cancer clinical trials. It inhibits extracellular signal regulating kinase (ERK/2) and activates caspase to dramatically inhibit ERK1/2 phosphorylation.

Clinical Research

In phase II clinical trials of radioiodine-refractory papillary thyroid carcinoma, 39 patients took daily oral doses of Selumetinib (100mg bid) for 28 days; results showed that 21 patients’ conditions stabilized (54%), 11 patients’ conditions worsened (28%), 49% patients’ conditions were stable for 16 weeks, 36% patients’ conditions were stable for 24 weeks, and survival terms did not progress to 32 weeks. Negative reactions mainly consisted of rashes (59%), diarrhea (44%), and weakness (41%). Some studies found that after treating 20 patients with thyroid cancer with Selumetinib (75mg bid) for 4 weeks, Selumetinib increased the iodine uptake and retention of patients with radioiodine-refractory papillary thyroid carcinoma. In a blind and random comparative study between a Selumetinib and Docetaxel (DOC) combination treatment group and DOC and placebo treatment group for 87 mutant NSCLSC patients, survival times were 9.4 months and 5.2 months, PFS were 5.3 months and 2.1 months, RR were 37% and 0%, thus showing dramatic differences. Selumetinib’s main negative reactions include neutrophil depletion, dermatitis, and respiratory failure.

Description

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).

Uses

Different sources of media describe the Uses of 606143-52-6 differently. You can refer to the following data:
1. 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.
2. It is a tight-binding, uncompetitive inhibitor of mitogen-activated protein kinase kinases (MEK) 1 and 2 currently in clinical development.

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.

References

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

Upstream product

• 606144-05-2 5-[(4-bromo-2-chlorophenyl)amino]-N-[2-(ethenyloxy)ethoxy]-4-fluoro-1-methyl-1H-benzimidazole-6-carboxamide 
• 1000340-06-6 methyl 5-[(4-bromophenyl)amino]-4-fluoro-1-methyl-1H-benzimidazole-6-carboxylate 
• 606144-02-9 methyl 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-1-methyl-1H-benzimidazole-6-carboxylate 
• 606093-58-7 4-Amino-3-fluoro-5-nitro-2-phenylamino-benzoic acid methyl ester 
• 606143-46-8 6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester 
• 606144-04-1 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-1-methyl-1H-benzimidazole-6-carboxylic acid 
• 3279-95-6 O-(2-hydroxyethyl)hydroxylamine 

Downstream Products

• 1535208-24-2 6-(4-bromo-2-chloroanilino)-7-fluoro-N-[2-(α-D-glucopyranosyloxy)ethoxy]-3-methylbenzimidazole-5-carboxamide 
• 1450912-89-6 C₂₄H₂₆BrClF₃N₇O₃ 
• 943332-08-9 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethoxy)amide hydrogen sulphate 
• 942275-12-9 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide p-toluenesulfonate 

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