| Stereochemistry | ABSOLUTE |
| Molecular Formula | C19H20F3IN2O5S |
| Molecular Weight | 572.337 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=C(NS(=O)(=O)C2(C[C@H](O)CO)CC2)C(NC3=CC=C(I)C=C3F)=C(F)C(F)=C1
InChI
InChIKey=RDSACQWTXKSHJT-NSHDSACASA-N
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
| Molecular Formula | C19H20F3IN2O5S |
| Molecular Weight | 572.337 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Refametinib (RDEA-119, BAY- 869766) is a highly potent and selective inhibitor of mitogen-activated ERK kinase (MEK1/2) activity, Refametinib binds to an allosteric pocket adjacent to the ATP binding site, locking the enzyme in a catalytically inactive conformation. This compound is highly efficacious at inhibiting cell proliferation in several tumor cell lines in vitro. In vivo, Refametinib exhibits potent activity in xenograft models of cancers. Ardea Biosciences (a subsidiary of AstraZeneca) and Bayer HealthCare are developing refametinib for the treatment of cancer. The sulfonamide agent was originally developed by Valeant Pharmaceuticals International. Refametinib is in phase II development for hepatocellular carcinoma, and phase I/II development for pancreatic cancer and other solid tumours.
Originator
Approval Year
Sourcing
PubMed
Sample Use Guides
Refametinib (RDEA-119, BAY- 869766) was administered orally daily in 28-day courses, with doses escalated to establish the maximum-tolerated dose (MTD). The MTD was 100 mg given once-daily or in two divided doses. The drug was well-tolerated, with good oral absorption, dose proportional pharmacokinetics, target inhibition at the MTD, and some evidence of clinical benefit across a range of tumor types.
Route of Administration:
Oral
Refametinib (RDEA-119, BAY- 869766) potently inhibited MEK activity as measured by phosphorylation of ERK1/2 across several human cancer cell lines of different tissue origins and BRAF mutational status with EC50 values ranging from 2.5 to 15.8 nM. RDEA119 inhibited 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. In contrast, RDEA119 had significantly less growth-inhibitory potency against cell lines with wild-type BRAF (A431 cells) or MDA-MB-231 cells harboring a BRAF mutation G464V that shows minimal (<2-fold increase) enhancement of inherent kinase activity. Interestingly, under anchorage-independent conditions, GI50 values for all cell lines tested were similar 40–84 nM.
