Refametinib
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MedKoo CAT#: 202431

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.


Price and Availability

Size
Price

10mg
Not available
100mg
USD 1650
1g
USD 4250
Size
Price

25mg
Not available
200mg
USD 2450
2g
USD 7650
Size
Price

50mg
Not available
500mg
USD 3450
5g
USD 14650

Refametinib (BAY 86-9766 or RDEA119) purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received. Delivery time: overnight (USA/Canada); 3-5 days (worldwide). Shipping fee: from $30.00 (USA); from $45.00 (Canada); from $70.00 (international).


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 202431
Name: Refametinib
CAS#: 923032-37-5
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


Technical Data

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).

Harmonized System Code:
293490


Additional Information

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 ).
 
 
 


References

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.