WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H202431
CAS#: 923032-37-5
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.
Hodoodo Cat#: H202431
Name: Refametinib
CAS#: 923032-37-5
Chemical Formula: C19H20F3IN2O5S
Exact Mass: 572.01
Molecular Weight: 572.340
Elemental Analysis: C, 39.87; H, 3.52; F, 9.96; I, 22.17; N, 4.89; O, 13.98; S, 5.60
Related CAS #: 923032-37-5
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
More Info: 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 (Nexavar®; Bayer HealthCare, Onyx Pharmaceuticals). (source: http://www.ardeabio.com/development-pipeline/cancer.htm ).
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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 |
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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.
2: Weekes CD, Von Hoff DD, Adjei AA, Leffingwell DP, Eckhardt SG, Gore L, Lewis KD, Weiss GJ, Ramanathan RK, Dy GK, Ma WW, Sheedy B, Iverson C, Miner JN, Shen Z, Yeh LT, Dubowy RL, Jeffers M, Rajagopalan P, Clendeninn NJ. Multicenter phase I trial of the mitogen-activated protein kinase 1/2 inhibitor BAY 86-9766 in patients with advanced cancer. Clin Cancer Res. 2013 Mar 1;19(5):1232-43. doi: 10.1158/1078-0432.CCR-12-3529. Epub 2013 Feb 22. PubMed PMID: 23434733.
3: Gorges TM, Schiller J, Schmitz A, Schuetzmann D, Schatz C, Zollner TM, Krahn T, von Ahsen O. Cancer therapy monitoring in xenografts by quantitative analysis of circulating tumor DNA. Biomarkers. 2012 Sep;17(6):498-506. doi: 10.3109/1354750X.2012.689133. Epub 2012 May 23. PubMed PMID: 22616911.
4: Liu Z, Xing M. Induction of sodium/iodide symporter (NIS) expression and radioiodine uptake in non-thyroid cancer cells. PLoS One. 2012;7(2):e31729. doi: 10.1371/journal.pone.0031729. Epub 2012 Feb 16. PubMed PMID: 22359623; PubMed Central PMCID: PMC3281006.
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.
9: Hou P, Bojdani E, Xing M. Induction of thyroid gene expression and radioiodine uptake in thyroid cancer cells by targeting major signaling pathways. J Clin Endocrinol Metab. 2010 Feb;95(2):820-8. doi: 10.1210/jc.2009-1888. Epub 2009 Dec 11. PubMed PMID: 20008023; PubMed Central PMCID: PMC2840852.
10: Iverson C, Larson G, Lai C, Yeh LT, Dadson C, Weingarten P, Appleby T, Vo T, Maderna A, Vernier JM, Hamatake R, Miner JN, Quart B. RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer. Cancer Res. 2009 Sep 1;69(17):6839-47. doi: 10.1158/0008-5472.CAN-09-0679. Epub 2009 Aug 25. PubMed PMID: 19706763.
