Refametinib | RDEA119 | BAY 86-9766 | CAS# 923032-37-5 | MEK inhibitor

MedKoo Cat#: 202431 | Name: Refametinib

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Refametinib

CAS#923032-37-5

Theoretical Analysis

MedKoo Cat#: 202431

Name: Refametinib

CAS#: 923032-37-5

Chemical Formula: C19H20F3IN2O5S

Exact Mass: 572.0090

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

Price and Availability

Size	Price	Availability
10mg	USD 150.00	2 Weeks
25mg	USD 250.00	2 Weeks
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,350.00	2 Weeks
500mg	USD 2,850.00	2 Weeks
1g	USD 4,350.00	2 Weeks
2g	USD 6,950.00	2 Weeks

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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 (NexavarÂ®; Bayer HealthCare, Onyx Pharmaceuticals). (source: http://www.ardeabio.com/development-pipeline/cancer.htm ).

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Refametinib is an allosteric, selective inhibitor of MEK1 and MEK2 (IC50s = 19 and 47 nM, respectively). It blocks phosphorylation of ERK1/2 across several human cancer cell lines differing in tissue origin and BRAF mutational status (EC50s = 2.5-16 nM), inhibiting cell cycling in cancer cells but not in primary cells. Refametinib has potential utility, particularly in combination therapy, in treating certain forms of cancer.

In vitro activity:

Refametinib exhibited potent antiproliferative activity in hepatocellular carcinoma (HCC) cell lines with half-maximal inhibitory concentration values ranging from 33 to 762 nM. Refametinib shows potent single-agent antitumor activity and acts synergistically in combination with sorafenib in preclinical HCC models. Reference: Neoplasia. 2013 Oct;15(10):1161-71. https://pubmed.ncbi.nlm.nih.gov/24204195/

In vivo activity:

In vivo, refametinib exhibits potent activity in xenograft models of melanoma, colon, and epidermal carcinoma. Refametinib exhibits complete suppression of ERK phosphorylation at fully efficacious doses in mice. Refametinib, an exquisitely selective, orally available MEK inhibitor, has been selected for clinical development because of its potency and favorable pharmacokinetic profile. Refametinib has the potential for use as a once- or twice-daily oral treatment for cancer. Reference: Cancer Res. 2009 Sep 1;69(17):6839-47. https://pubmed.ncbi.nlm.nih.gov/19706763/

	Solvent	mg/mL	mM
Solubility
	DMF	15.0	26.21
	DMSO	1.0	1.75
	Ethanol	20.0	34.94

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

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

Formulation protocol:

1. Schmieder R, Puehler F, Neuhaus R, Kissel M, Adjei AA, Miner JN, Mumberg D, Ziegelbauer K, Scholz A. Allosteric MEK1/2 inhibitor refametinib (BAY 86-9766) in combination with sorafenib exhibits antitumor activity in preclinical murine and rat models of hepatocellular carcinoma. Neoplasia. 2013 Oct;15(10):1161-71. doi: 10.1593/neo.13812. PMID: 24204195; PMCID: PMC3819632. 2. O'Shea J, Cremona M, Morgan C, Milewska M, Holmes F, Espina V, Liotta L, O'Shaughnessy J, Toomey S, Madden SF, Carr A, Elster N, Hennessy BT, Eustace AJ. A preclinical evaluation of the MEK inhibitor refametinib in HER2-positive breast cancer cell lines including those with acquired resistance to trastuzumab or lapatinib. Oncotarget. 2017 Jul 22;8(49):85120-85135. doi: 10.18632/oncotarget.19461. PMID: 29156708; PMCID: PMC5689598. 3. Lim HY, Merle P, Weiss KH, Yau T, Ross P, Mazzaferro V, Blanc JF, Ma YT, Yen CJ, Kocsis J, Choo SP, Sukeepaisarnjaroen W, Gérolami R, Dufour JF, Gane EJ, Ryoo BY, Peck-Radosavljevic M, Dao T, Yeo W, Lamlertthon W, Thongsawat S, Teufel M, Roth K, Reis D, Childs BH, Krissel H, Llovet JM. Phase II Studies with Refametinib or Refametinib plus Sorafenib in Patients with RAS-Mutated Hepatocellular Carcinoma. Clin Cancer Res. 2018 Oct 1;24(19):4650-4661. doi: 10.1158/1078-0432.CCR-17-3588. Epub 2018 Jun 27. PMID: 29950351. 4. 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. PMID: 19706763.

In vitro protocol:

In vivo protocol:

1. Lim HY, Merle P, Weiss KH, Yau T, Ross P, Mazzaferro V, Blanc JF, Ma YT, Yen CJ, Kocsis J, Choo SP, Sukeepaisarnjaroen W, Gérolami R, Dufour JF, Gane EJ, Ryoo BY, Peck-Radosavljevic M, Dao T, Yeo W, Lamlertthon W, Thongsawat S, Teufel M, Roth K, Reis D, Childs BH, Krissel H, Llovet JM. Phase II Studies with Refametinib or Refametinib plus Sorafenib in Patients with RAS-Mutated Hepatocellular Carcinoma. Clin Cancer Res. 2018 Oct 1;24(19):4650-4661. doi: 10.1158/1078-0432.CCR-17-3588. Epub 2018 Jun 27. PMID: 29950351. 2. 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. PMID: 19706763.

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