[CAS NO. 923032-37-5] Refametinib (RDEA119)

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PRODUCTS SPECIFICATIONS [923032-37-5]

Catalog

SLK-S1089

Brand

Selleck

CAS

923032-37-5

DESCRIPTION [923032-37-5]

Overview

MDL	MFCD18633256
Molecular Weight	572.34
Molecular Formula	C19H20F3IN2O5S
SMILES	S(NC1=C(NC2=C(F)C=C(I)C=C2)C(F)=C(F)C=C1OC)(=O)(=O)C3(C[C@@H](CO)O)CC3

For research use only.

Storage

3 years,-20°C,powder
1 years,-80°C,in solvent

Shipping

Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Concentration Volume Mass	1 mg	5 mg	10 mg
1 mM	1.7472 mL	8.7361 mL	17.4721 mL
5 mM	0.3494 mL	1.7472 mL	3.4944 mL
10 mM	0.1747 mL	0.8736 mL	1.7472 mL
50 mM	0.0349 mL	0.1747 mL	0.3494 mL

Description

Refametinib (RDEA119, Bay 86-9766) is a potent, ATP non-competitive and highly selective inhibitor of and with of 19 nM and 47 nM, respectively.

Targets

MEK1 ^[1] (Cell-free assay)	MEK2 ^[1] (Cell-free assay)
19 nM	47 nM

In vitro

RDEA119 is selectively bound directly to an allosteric pocket in the MEK1/2 enzymes, and highly efficacious at inhibiting cell proliferation in several tumor cell lines, including A375, SK-MEI-28, Colo205, HT-29 and BxPC3. RDEA119 inhibits anchorage-dependent growth of human cancer cell lines harboring the gain-of-function V600E BRAF mutant with GI50 values ranging from 67 to 89 nM. Under anchorage-independent conditions, GI50 values for all cell lines tested are similar (40-84 nM). RDEA119 shows a tissue selectivity that reduces its potential for central nervous system–related side effects. RDEA119 potently inhibits the proliferation of the 4 cell lines that harbored BRAF mutation but has no or modest effects on the other 4 cells that harbored wild-type BRAF (IC50 of 0.034-0.217 μM vs. 1.413-34.120 μM). This inhibitory effect of RDEA119 in selected cell lines OCUT1 (BRAF V600E(+), PIK3CA H1047R(+)) and SW1376 (BRAF V600E(+)) is enhanced by combination with the mTOR inhibitor, temsirolimus. RDEA119 and temsirolimus also show synergistic effects on autophagic death of OCUT1 and KAT18 cells selectively tested.

In vivo

Oral administration of RDEA119 at 50 mg/kg on a once daily × 14 schedule leads to a 68% tumor growth inhibition (TGI) in human melanoma A375 tumor model. Oral administration of RDEA119 at 25 mg/kg on a once a once daily × 14 schedule leads to a 123% TGI in human colon carcinoma Colo205 tumor model (TGI > 100% occurs when the tumor shrinks below its starting volume). A dose of 25 mg/kg once daily × 14 produces 56% and 67% TGI for HT-29 and A431 tumors, respectively.

References

[1] Iverson C, et al, Cancer Res, 2009, 69(17), 6839-6847.
[2] Liu D, et al, Int J Cancer, 2010, 127(12), 2965-2973.

Synonyms

Cyclopropanesulfonamide, N-[3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-methoxyphenyl]-1-[(2S)-2,3-dihydroxypropyl]-

N-[3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-methoxyphenyl]-1-[(2S)-2,3-dihydroxypropyl]cyclopropanesulfonamide

RDEA 119

BAY 8697661

BAY 869766

Refametinib

N-[3,4-Difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]-1-[(2S)-2,3-dihydroxypropyl]cyclopropane-1-sulfonamide

Bay 86-9766