Selumetinib sulfate (AZD6244 sulfate)

Alias: ARRY-142886 sulfate; AZD6244 sulfate; AZD-6244; AZD 6244; ARRY142886; ARRY 142886; ARRY-142886; ARRY886; ARRY-886; ARRY 886sulfate
Cat No.:V37565 Purity: ≥98%
Selumetinib sulfate (also known as AZD6244 sulfate; ARRY-142886 sulfate) is a novel, potent, highly selective, orally bioavailable, andnon-ATP-competitivesmall molecule MEK1 inhibitor with IC50 of 14 nM in cell-free assays and with anticancer activity, it also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc.
Selumetinib sulfate (AZD6244 sulfate) Chemical Structure CAS No.: 943332-08-9
Product category: MEK
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
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Other Forms of Selumetinib sulfate (AZD6244 sulfate):

  • Selumetinib (AZD-6244; ARRY142886)
Official Supplier of:
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Top Publications Citing lnvivochem Products
Product Description

Selumetinib sulfate (also known as AZD6244 sulfate; ARRY-142886 sulfate) is a novel, potent, highly selective, orally bioavailable, and non-ATP-competitive small molecule MEK1 inhibitor with IC50 of 14 nM in cell-free assays and with anticancer activity, it also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. Selumetinib prevents the activation of MEK1/2-dependent effector proteins and transcription factors, which may prevent the proliferation of MEK-overexpressing tumor cells by preventing the activation of MEK1/2-dependent effector proteins and transcription factors.

Biological Activity I Assay Protocols (From Reference)
Targets
MEK1 (IC50 = 14 nM); MEK1 (Kd = 99 nM); MEK2 (Kd = 530 nM)
ln Vitro
NVP-BHG712 dose-dependently inhibited the autophosphorylation of EphRs in Hek293 cells transfected with various EphRs. When compared to EphB2, EphA2, EphB3, and NVP-BHG712, EphB4 exhibited a stronger inhibitory preference. AZD6244 inhibits the phosphorylation of ERK1/2 at IC50 concentrations below 40 nM and is not ATP-competitive. Inhibiting ERK1/2 and p90RSK phosphorylation, as well as elevating caspase-3 and caspase-7 cleavage and cleaved poly(ADP)ribose polymerase, all contribute to AZD6244's ability to stop the growth of primary HCC cells. Phosphatidylinositol 3-kinase, MEK5/ERK5 and p38 pathways are not significantly affected by AZD6244. Ras mutations and Raf mutations both affect AZD6244's sensitivity to breast cancer cell lines and NSCLC cell lines, respectively.
ln Vivo
AZD6244 significantly inhibits phosphorylation of ERK1/2 in 2-1318, 5-1318, 26-1004 and 4-1318 xenografts and induces apoptosis in primary 2-1318 cells by activating the caspase pathway. At a dose of 100 mg/kg, AZD6244 could slow the growth of the tumor in the HT-29 xenograft, a colorectal tumor model with a B-Raf mutation; this tumor growth inhibition is superior to that of Gemcitabine. Apoptosis and the down-regulation of cell cycle regulators like cyclin D1, Cdc-2, CDK2 and 4, cyclin B1, and c-Myc are associated with increased apoptosis, which is why AZD6244 could inhibit the growth of HCC xenograft tumors in the absence of these factors.
Enzyme Assay
MEK1 molecules are immunoprecipitated using anti-MEK1 antibodies. Measuring MEK kinase activity involves using immuno-isolated MEK1 to activate recombinant ERK1 in a coupled assay with MBP as the end point. Before being exposed to X-ray film, phosphorylated MBP is resolved on a 14% SDS-PAGE gel and vacuum dried.
Cell Assay
Cells are seeded at a density of 2.0 × 104 (Primary HCC cell lines, including 2-1318, 4-1318, and 26-1004 cells). The cells are rinsed twice with culture media after 48 hours of incubation. AZD6244 is applied to cells at various concentrations for 24 or 48 hours. The 3-(4,5-dimethylthiazol-2y1)-2,5-diphenyltetrazolium bromide (MTT) assay is used to determine the viability of cells. A bromodeoxyuridine kit is used to measure cell proliferation.
Animal Protocol
Dissolved in water; 50 or 100mg/kg; Oral gavage
HCC xenografts in mice homozygous for the SCID (severe combined immunodeficiency) mutation
References

[1]. Targeted inhibition of the extracellular signal-regulated kinase kinase pathway with AZD6244 (ARRY-142886) in the treatment of hepatocellular carcinoma. Mol Cancer Therapy, 2007, 6 (1), 138-146 .

[2]. Identification of common predictive markers of in vitro response to the Mek inhibitor selumetinib (AZD6244; ARRY-142886) in human breast cancer and non-small cell lung cancer cell lines. Mol Cancer Thera, 2010, 9 (7), 1985-1994.

[3]. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin Cancer Res, 2007, 13 (5), 1576-1583.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C₁₇H₁₇BRCLFN₄O₇S
Molecular Weight
555.76
Exact Mass
553.96739
CAS #
943332-08-9
Appearance
Solid
SMILES
CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)Cl)C(=O)NOCCO.OS(=O)(=O)O
InChi Key
GRKFGZYYYYISDX-UHFFFAOYSA-N
InChi Code
InChI=1S/C17H15BrClFN4O3.H2O4S/c1-24-8-21-16-13(24)7-10(17(26)23-27-5-4-25)15(14(16)20)22-12-3-2-9(18)6-11(12)19;1-5(2,3)4/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26);(H2,1,2,3,4)
Chemical Name
6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide;sulfuric acid
Synonyms
ARRY-142886 sulfate; AZD6244 sulfate; AZD-6244; AZD 6244; ARRY142886; ARRY 142886; ARRY-142886; ARRY886; ARRY-886; ARRY 886sulfate
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: >100 mg/mL
Water: N/A
Ethanol: N/A
Solubility (In Vivo)
4% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL
 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.7993 mL 8.9967 mL 17.9934 mL
5 mM 0.3599 mL 1.7993 mL 3.5987 mL
10 mM 0.1799 mL 0.8997 mL 1.7993 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
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Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03213691 Active
Recruiting
Drug: Selumetinib Sulfate
Drug: Selumetinib
Recurrent Neuroblastoma
Refractory Neuroblastoma
National Cancer Institute
(NCI)
July 24, 2017 Phase 2
NCT02839720 Active
Recruiting
Other: Laboratory Biomarker
Analysis
Drug: Selumetinib Sulfate
Optic Nerve Glioma
Cutaneous Neurofibroma
National Cancer Institute
(NCI)
August 26, 2017 Phase 2
NCT01362803 Active
Recruiting
Drug: AZD6244 Neurofibromatosis 1
NF1
National Cancer Institute
(NCI)
September 21, 2011 Phase 1
Phase 2
NCT01364051 Active
Recruiting
Drug: Cediranib
Drug: Selumetinib
Metastatic Melanoma
Refractory Malignant
National Cancer Institute
(NCI)
May 25, 2011 Phase 1
NCT02407405 Active
Recruiting
Drug: Selumetinib Neurofibromatosis 1
(NF1)
Plexiform Neurofibromas
(PN)
National Cancer Institute
(NCI)
January 7, 2016 Phase 2
Biological Data
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