Basic information Indications and Usage Mechanisms of Action Clinical Research Safety Supplier Related
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Selumetinib

Selumetinib is an oral, potent selective mitogen activated protein kinase kinase (MEK) inhibitor, which has been shown to be effective against MEK-dependent tumours. It is intended to treat metastatic uveal melanoma, a rare malignancy that affects the eyes. It is the most common adult intraocular tumour; it arises from melanocytes in the uvea and affects mostly those from White ethnic groups, particularly those with light coloured irises.

Basic information Indications and Usage Mechanisms of Action Clinical Research Safety Supplier Related

Selumetinib 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
  • 6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide
  • Selumetinib AZD624
  • 5-[(4-Bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-car
  • Selumetinib, 99%, a highly selective MEK1 inhibitor
  • Selumetinib, Free BaseAZD6244ARRY-142886
CAS:
606143-52-6
MF:
C17H15BrClFN4O3
MW:
457.68
EINECS:
207-313-3
Product Categories:
  • MAPK
  • Inhibitors
  • Aromatics
  • Heterocycles
  • apis
  • Antineoplastic
  • API
  • Inhibitor
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • Research
Mol File:
606143-52-6.mol
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Selumetinib Chemical Properties

Melting point:
>219°C (dec.)
Density 
1.69
storage temp. 
-20°
solubility 
Soluble in DMSO (up to 50 mg/ml) or in Ethanol (up to 2 mg/ml)
form 
Beige powder.
pka
14.20±0.10(Predicted)
color 
White
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.
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Safety Information

HS Code 
29349990
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Selumetinib Usage And Synthesis

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

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.

Uses

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

SelumetinibSupplier

Wuhan belka pharmaceutical co., LTD Gold
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Products Intro
CAS:606143-52-6
Purity:99% HPLC Package:1g,5g,10g,50g,100g,500g;1000g
Hubei Junxian Biotechnology Co., Ltd Gold
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Product Name:Selumetinib
CAS:606143-52-6
Purity:99.5%
Jurong Coupling Biotechnology Co., Ltd. Gold
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Product Name:Selumetinib
CAS:606143-52-6
Purity:99 Package:20g
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027-51903003 15926256169
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Product Name:AZD6244
CAS:606143-52-6
Purity:99% Package:10G 100G 500G
Ningbo Risheng Pharmaceutical Technology Co., Ltd. Gold
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19906600019
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Product Name:Selumetinib;AZD6244
CAS:606143-52-6
Purity:99%+ HPLC Remarks:kg