606143-52-6 | Selumetinib

Packsize	Purity	Availability	Price	Discounted Price
10mg	≥95%	in stock	$42.00	$29.00
25mg	98%(HPLC)powder	in stock	$42.00	$30.00
100mg	98%(HPLC)powder	in stock	$116.00	$81.00
250mg	98%(HPLC)powder	in stock	$285.00	$199.00
1g	98%(HPLC)powder	in stock	$569.00	$398.00

Description

• Catalog Number: AB49439
• Chemical Name: Selumetinib
• CAS Number: 606143-52-6
• Molecular Formula: C17H15BrClFN4O3
• Molecular Weight: 457.6814
• MDL Number: MFCD11977472
• SMILES: OCCONC(=O)c1cc2n(C)cnc2c(c1Nc1ccc(cc1Cl)Br)F
• NSC Number: 741078

Computed Properties

• Complexity: 523
• Covalently-Bonded Unit Count: 1
• Heavy Atom Count: 27
• Hydrogen Bond Acceptor Count: 6
• Hydrogen Bond Donor Count: 3
• Rotatable Bond Count: 6
• XLogP3: 3.6

Literature

• Paradoxical activation of MEK/ERK signaling induced by B-Raf inhibition enhances DR5 expression and DR5 activation-induced apoptosis in Ras-mutant cancer cells.

  Scientific reports 20160101

• Harmine Induces Adipocyte Thermogenesis through RAC1-MEK-ERK-CHD4 Axis.

  Scientific reports 20160101

• Targeting TBK1 inhibits migration and resistance to MEK inhibitors in mutant NRAS melanoma.

  Molecular cancer research : MCR 20141001

• Synergistic induction of human cathelicidin antimicrobial peptide gene expression by vitamin D and stilbenoids.

  Molecular nutrition & food research 20140301

• Flavanoids induce expression of the suppressor of cytokine signalling 3 (SOCS3) gene and suppress IL-6-activated signal transducer and activator of transcription 3 (STAT3) activation in vascular endothelial cells.

  The Biochemical journal 20130901

• Identification of potent Yes1 kinase inhibitors using a library screening approach.

  Bioorganic & medicinal chemistry letters 20130801

• Optimization of allosteric MEK inhibitors. Part 1: Venturing into underexplored SAR territories.

  Bioorganic & medicinal chemistry letters 20130415

• MEK and the inhibitors: from bench to bedside.

  Journal of hematology & oncology 20130101

• Combined PI3K/mTOR and MEK inhibition provides broad antitumor activity in faithful murine cancer models.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20121001

• Combination of the ERK inhibitor AZD6244 and low-dose sorafenib in a xenograft model of human renal cell carcinoma.

  International journal of oncology 20120801

• Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification.

  Molecular cancer therapeutics 20120701

• A phase II open-label randomized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY-142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy.

  Investigational new drugs 20120601

• Intrinsic resistance to selumetinib, a selective inhibitor of MEK1/2, by cAMP-dependent protein kinase A activation in human lung and colorectal cancer cells.

  British journal of cancer 20120508

• Dynamic reprogramming of the kinome in response to targeted MEK inhibition in triple-negative breast cancer.

  Cell 20120413

• The synergistic interaction of MEK and PI3K inhibitors is modulated by mTOR inhibition.

  British journal of cancer 20120410

• Enhanced apoptosis and tumor growth suppression elicited by combination of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055).

  Cancer research 20120401

• Cancer: Clinical trials unite mice and humans.

  Nature 20120328

• A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response.

  Nature 20120318

• Combined MEK and VEGFR inhibition in orthotopic human lung cancer models results in enhanced inhibition of tumor angiogenesis, growth, and metastasis.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20120315

• The MEK1/2 inhibitor, selumetinib (AZD6244; ARRY-142886), enhances anti-tumour efficacy when combined with conventional chemotherapeutic agents in human tumour xenograft models.

  British journal of cancer 20120227

• Preclinical activity of the rational combination of selumetinib (AZD6244) in combination with vorinostat in KRAS-mutant colorectal cancer models.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20120215

• The Akt inhibitor MK2206 synergizes, but perifosine antagonizes, the BRAF(V600E) inhibitor PLX4032 and the MEK1/2 inhibitor AZD6244 in the inhibition of thyroid cancer cells.

  The Journal of clinical endocrinology and metabolism 20120201

• Sorafenib and Mek inhibition is synergistic in medullary thyroid carcinoma in vitro.

  Endocrine-related cancer 20120201

• MEK1/2 inhibitor selumetinib (AZD6244) inhibits growth of ovarian clear cell carcinoma in a PEA-15-dependent manner in a mouse xenograft model.

  Molecular cancer therapeutics 20120201

• Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20120115

• Impact of combined mTOR and MEK inhibition in uveal melanoma is driven by tumor genotype.

  PloS one 20120101

• A phase I, open-label, randomized crossover study to assess the effect of dosing of the MEK 1/2 inhibitor Selumetinib (AZD6244; ARRY-142866) in the presence and absence of food in patients with advanced solid tumors.

  Cancer chemotherapy and pharmacology 20111201

• Small molecule inhibition of the steroid receptor coactivators, SRC-3 and SRC-1.

  Molecular endocrinology (Baltimore, Md.) 20111201

• Cytokinetically quiescent (G0/G1) human multiple myeloma cells are susceptible to simultaneous inhibition of Chk1 and MEK1/2.

  Blood 20111110

• Comprehensive analysis of kinase inhibitor selectivity.

  Nature biotechnology 20111030

• A Phase II, open-label, randomised study to assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY-142886) versus capecitabine monotherapy in patients with colorectal cancer who have failed one or two prior chemotherapeutic regimens.

  Investigational new drugs 20111001

• Exon capture analysis of G protein-coupled receptors identifies activating mutations in GRM3 in melanoma.

  Nature genetics 20110925

• Simultaneous exposure of transformed cells to SRC family inhibitors and CHK1 inhibitors causes cell death.

  Cancer biology & therapy 20110801

• Enhancement of 5-fluorouracil-induced in vitro and in vivo radiosensitization with MEK inhibition.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20110801

• Nilotinib alone or in combination with selumetinib is a drug candidate for neurofibromatosis type 2.

  Neuro-oncology 20110701

• Phase II study of the mitogen-activated protein kinase 1/2 inhibitor selumetinib in patients with advanced hepatocellular carcinoma.

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20110610

• NSCLC drug targets acquire new visibility.

  Journal of the National Cancer Institute 20110302

• Regulation of mesenchymal stem cell activity by endothelial cells.

  Stem cells and development 20110301

• Pharmacokinetics and pharmacodynamics of AZD6244 (ARRY-142886) in tumor-bearing nude mice.

  Cancer chemotherapy and pharmacology 20110201

• Could HBx protein expression affect signal pathway inhibition by gefitinib or selumetinib, a MEK inhibitor, in hepatocellular carcinoma cell lines?

  Journal of Korean medical science 20110201

• EZH2 promotes expansion of breast tumor initiating cells through activation of RAF1-β-catenin signaling.

  Cancer cell 20110118

• MEK1/2 inhibitors AS703026 and AZD6244 may be potential therapies for KRAS mutated colorectal cancer that is resistant to EGFR monoclonal antibody therapy.

  Cancer research 20110115

• Reversing melanoma cross-resistance to BRAF and MEK inhibitors by co-targeting the AKT/mTOR pathway.

  PloS one 20110101

• Vertical targeting of the phosphatidylinositol-3 kinase pathway as a strategy for treating melanoma.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20101215

• Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.

  Chemistry & biology 20101124

• A phase II, open-label, randomized study to assess the efficacy and safety of AZD6244 (ARRY-142886) versus pemetrexed in patients with non-small cell lung cancer who have failed one or two prior chemotherapeutic regimens.

  Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 20101001

• Inhibition of MEK/ERK signaling induces apoptosis of acute myelogenous leukemia cells via inhibition of eukaryotic initiation factor 4E-binding protein 1 and down-regulation of Mcl-1.

  Apoptosis : an international journal on programmed cell death 20100701

• AZD6244 (ARRY-142886) enhances the antitumor activity of rapamycin in mouse models of human hepatocellular carcinoma.

  Cancer 20100301

• The first-in-human study of the hydrogen sulfate (Hyd-sulfate) capsule of the MEK1/2 inhibitor AZD6244 (ARRY-142886): a phase I open-label multicenter trial in patients with advanced cancer.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20100301

• Mitogen-activated protein/extracellular signal-regulated kinase kinase inhibition results in biphasic alteration of epidermal homeostasis with keratinocytic apoptosis and pigmentation disorders.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20100201

• Targeting ERK1/2 activation and proliferation in human primary schwannoma cells with MEK1/2 inhibitor AZD6244.

  Neurobiology of disease 20100101

• AZD6244 enhances the anti-tumor activity of sorafenib in ectopic and orthotopic models of human hepatocellular carcinoma (HCC).

  Journal of hepatology 20100101

• Apoptosis induction by MEK inhibition in human lung cancer cells is mediated by Bim.

  PloS one 20100101

• Combination treatment with MEK and AKT inhibitors is more effective than each drug alone in human non-small cell lung cancer in vitro and in vivo.

  PloS one 20100101

• Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study.

  British journal of cancer 20091117

• Dual inhibition of mitogen-activated protein kinase kinase and mammalian target of rapamycin in differentiated and anaplastic thyroid cancer.

  The Journal of clinical endocrinology and metabolism 20091001

• A combined, rational approach towards inhibition of the MEK-ERK and mTOR pathways in pancreatic ductal adenocarcinoma: promise or deja vu?

  Cancer biology & therapy 20091001

• Effects of combined inhibition of MEK and mTOR on downstream signaling and tumor growth in pancreatic cancer xenograft models.

  Cancer biology & therapy 20091001

• Blockade of MEK signaling potentiates 5-Aza-2'-deoxycytidine-induced apoptosis and upregulation of p21(waf1) in acute myelogenous leukemia cells.

  International journal of cancer 20090901

• Inhibition of MEK signaling enhances the ability of cytarabine to induce growth arrest and apoptosis of acute myelogenous leukemia cells.

  Apoptosis : an international journal on programmed cell death 20090901

• AZD6244 (ARRY-142886) enhances the therapeutic efficacy of sorafenib in mouse models of gastric cancer.

  Molecular cancer therapeutics 20090901

• Combination of EGFR and MEK1/2 inhibitor shows synergistic effects by suppressing EGFR/HER3-dependent AKT activation in human gastric cancer cells.

  Molecular cancer therapeutics 20090901

• Trial offers early test case for personalized medicine.

  Journal of the National Cancer Institute 20090204

• Inhibition of MEK/ERK signaling synergistically potentiates histone deacetylase inhibitor-induced growth arrest, apoptosis and acetylation of histone H3 on p21waf1 promoter in acute myelogenous leukemia cell.

  Leukemia 20080701

• Advances in the development of cancer therapeutics directed against the RAS-mitogen-activated protein kinase pathway.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20080615

• Blockade of MEK/ERK signaling enhances sunitinib-induced growth inhibition and apoptosis of leukemia cells possessing activating mutations of the FLT3 gene.

  Leukemia research 20080601

• BRAFV600E mutation is associated with preferential sensitivity to mitogen-activated protein kinase kinase inhibition in thyroid cancer cell lines.

  The Journal of clinical endocrinology and metabolism 20080601

• The mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor AZD6244 (ARRY-142886) induces growth arrest in melanoma cells and tumor regression when combined with docetaxel.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20080101

• Targeting MEK induces myeloma-cell cytotoxicity and inhibits osteoclastogenesis.

  Blood 20070901

• AZD6244 and doxorubicin induce growth suppression and apoptosis in mouse models of hepatocellular carcinoma.

  Molecular cancer therapeutics 20070901

• 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/pharmacodynamic relationship, and potential for combination in preclinical models.

  Molecular cancer therapeutics 20070801

• ZD6474 induces growth arrest and apoptosis of human leukemia cells, which is enhanced by concomitant use of a novel MEK inhibitor, AZD6244.

  Leukemia 20070601

• Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20070301

• Targeted inhibition of the extracellular signal-regulated kinase kinase pathway with AZD6244 (ARRY-142886) in the treatment of hepatocellular carcinoma.

  Molecular cancer therapeutics 20070101

• Targeted agents for the treatment of advanced renal cell carcinoma.

  Current drug targets 20051101

• Mutations of the BRAF gene in human cancer.

  Nature 20020627