WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 202431
Description: Refametinib, also known as RDEA119, BAY 86-9766, is an orally bioavailable selective MEK inhibitor with potential antineoplastic activity. MEK inhibitor RDEA119 specifically inhibits mitogen-activated protein kinase kinase 1 (MAP2K1 or MAPK/ERK kinase 1), resulting in inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK, a dual specificity threonine/tyrosine kinase, is a key component of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth; constitutive activation of this pathway has been implicated in many cancers.
MedKoo Cat#: 202431
Chemical Formula: C19H20F3IN2O5S
Exact Mass: 572.00897
Molecular Weight: 572.34
Elemental Analysis: C, 39.87; H, 3.52; F, 9.96; I, 22.17; N, 4.89; O, 13.98; S, 5.60
Synonym: RDEA119; RDEA-119; RDEA 119; BAY 869766; BAY-69766; BAY869766; BAY 86 9766; BAY 86-9766; BAY86-9766; BAY 869766
IUPAC/Chemical Name: (S)-N-(3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide
InChi Key: RDSACQWTXKSHJT-NSHDSACASA-N
InChi Code: InChI=1S/C19H20F3IN2O5S/c1-30-15-7-13(21)16(22)18(24-14-3-2-10(23)6-12(14)20)17(15)25-31(28,29)19(4-5-19)8-11(27)9-26/h2-3,6-7,11,24-27H,4-5,8-9H2,1H3/t11-/m0/s1
SMILES Code: O=S(C1(C[C@H](O)CO)CC1)(NC2=C(OC)C=C(F)C(F)=C2NC3=CC=C(I)C=C3F)=O
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 572.34 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
1: Wylie-Sears J, Levine RA, Bischoff J. Losartan inhibits endothelial-to-mesenchymal transformation in mitral valve endothelial cells by blocking transforming growth factor-β-induced phosphorylation of ERK. Biochem Biophys Res Commun. 2014 Mar 12. pii: S0006-291X(14)00445-8. doi: 10.1016/j.bbrc.2014.03.014. [Epub ahead of print] PubMed PMID: 24632204.
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5: Holm TM, Habashi JP, Doyle JJ, Bedja D, Chen Y, van Erp C, Lindsay ME, Kim D, Schoenhoff F, Cohn RD, Loeys BL, Thomas CJ, Patnaik S, Marugan JJ, Judge DP, Dietz HC. Noncanonical TGFβ signaling contributes to aortic aneurysm progression in Marfan syndrome mice. Science. 2011 Apr 15;332(6027):358-61. doi: 10.1126/science.1192149. PubMed PMID: 21493862; PubMed Central PMCID: PMC3111087.
6: Diep CH, Munoz RM, Choudhary A, Von Hoff DD, Han H. Synergistic effect between erlotinib and MEK inhibitors in KRAS wild-type human pancreatic cancer cells. Clin Cancer Res. 2011 May 1;17(9):2744-56. doi: 10.1158/1078-0432.CCR-10-2214. Epub 2011 Mar 8. PubMed PMID: 21385921; PubMed Central PMCID: PMC3265169.
7: Liu D, Xing J, Trink B, Xing M. BRAF mutation-selective inhibition of thyroid cancer cells by the novel MEK inhibitor RDEA119 and genetic-potentiated synergism with the mTOR inhibitor temsirolimus. Int J Cancer. 2010 Dec 15;127(12):2965-73. doi: 10.1002/ijc.25304. PubMed PMID: 21351275; PubMed Central PMCID: PMC2916062.
8: Chang Q, Chapman MS, Miner JN, Hedley DW. Antitumour activity of a potent MEK inhibitor RDEA119/BAY 869766 combined with rapamycin in human orthotopic primary pancreatic cancer xenografts. BMC Cancer. 2010 Sep 28;10:515. doi: 10.1186/1471-2407-10-515. PubMed PMID: 20920162; PubMed Central PMCID: PMC2955043.
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BAY 86-9766, formerly known as RDEA119, is currently being developed by Ardea. BAY 86-9766 is a potent, non-ATP competitive, highly-selective inhibitor of MEK. According to Ardea Inc's website, preclinical and clinical data suggest that BAY 86-9766 has favorable properties, including once-daily, oral dosing, excellent selectivity and limited retention in the brain, which may result in a reduced risk of central nervous system (CNS) side effects at doses expected to be effective, a problem associated with other members of this class of compounds. In addition, BAY 86-9766 has been shown to suppress tumor cell growth in-vitro and in-vivo. Phase 1 data have demonstrated that BAY 86-9766 has a long half-life and favorable pharmacokinetic properties, allowing for once-daily oral dosing. Preclinical in vitro and in vivo oncology studies have demonstrated significant potential synergy across multiple tumor types when BAY 86-9766 is used in combination with other approved anti-cancer therapeutics, including sorafenib (NexavarÂ®; Bayer HealthCare, Onyx Pharmaceuticals). (source: http://www.ardeabio.com/development-pipeline/cancer.htm ).