N-[(2R)-2,3-Dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-benzamide

Non-ATP-competitive mitogen-activated protein kinase kinase MEK1/2 inhibitor IC50 = 1 nMin in vitro assay and 0.43 nM in a cell-based assay

OTAVAchemicals Catalogue Number: 7070707062

CAS Registry Number: 391210-10-9

Purity: 98% (HPLC)

5-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}-N-(2-morpholin-4-ylethyl)-1,3,4-oxadiazol-2-amine

Molecular Weight: 545.3063

OTAVAchemicals Catalogue Number: 7070707138

CAS Registry Number: 548756-68-9

Purity: 99% (HPLC)

5-[(4-Bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide

inhibitor of MEK1/2 kinases, effectively inhibited the proliferation of acute biphenotypic leukemia MV4-11 and acute monocytic leukemia MOLM13 cells. The concentrations that inhibited 50% growth were approximately 0.3 and 1.2 µM, respectively, as measured by thymidine uptake on day 2 of culture. AZD6244 potently down-regulated the levels of phospho-ERK1/2 and its downstream effector, p-p70S6K, in the MV4-11 and MOLM13 cells as measured by Western blot analysis. Four BRAF mutant lines exhibited growth inhibition at low doses of the drug, with GI50 concentrations ranging from 14 to 50 nM, predominantly via a G0/G1 arrest, comparable with findings in a sensitive BRAF mutant melanoma cell line. In contrast, two BRAF wild-type lines were significantly less sensitive, with GI50 values greater than 200 nM. Nude mouse xenograft tumors derived from the BRAF mutant line ARO exhibited dosedependent growth inhibition by AZD6244, with effective treatment at 10 mg/kg by oral gavage. This effect was primarily cytostatic and associated with marked inhibition of ERK phosphorylation.

OTAVAchemicals Catalogue Number: 1183194

CAS Registry Number: 606143-52-6

Purity: 97%+ (HPLC)