BMS-345541 is a highly selective inhibitor of the catalytic subunits of IKK-2 and IKK-1 with IC50 of 0.3 μM and 4 μM, respectively.
Product Name: BMS-345541 |Catalog Number: DC8761 |CAS 547757-23-3 |Other names: BMS345541 hydrochloride; BMS-345541 hydrochloride; BMS 345541 hydrochloride |Chemical Name: |Molecule Formular: C14H18ClN5 |MW: 291.78
BMS-345541 is a highly selective inhibitor of the catalytic subunits of IKK-2 and IKK-1 with IC50 of 0.3 μM and 4 μM, respectively.in vitro: BMS-345541 dose-dependently inhibits the TNF-α-stimulated phosphorylation of IκBα in THP-1 monocytic cells with an IC50 of ~4 μM. BMS-345541 inhibits lipopolysaccharide-stimulated tumor necrosis factorα, interleukin-1β, interleukin-8, and interleukin-6 in THP-1 cells with IC50 values in the 1- to 5 μM range. BMS-345541 binds in a mutually exclusive manner with respect to a peptide inhibitor corresponding to amino acids 26 - 42 of IκBα with Ser-32 and Ser-36 changed to aspartates and in a non-mutually exclusive manner with respect to ADP. BMS-345541 binds to similar allosteric sites on IKK-1 and IKK-2, which then affects the active sites of the subunits differently. BMS-345541 (10 μM) inhibits growth of Normal human epidermal melanocytes, and metastatic melanoma cells (SK-MEL-5, A375, and Hs 294T) by 96% and 99% at 72h, respectively. Application of 100 μM of BMS-345541 to SK-MEL-5 cell culture results in 87% apoptotic cells at 24 h through caspase-independent and AIF-dependent mitochondria-mediated manner. BMS-345541 treatment (10 μM) results in 76% and 95% reduction in IKK activities and NF-kB activity, as well as CXCL1 production. BMS-345541 inhibits the TNFα-induced expression of both ICAM-1 and VCAM-1 in human umbilical vein endothelial cells with IC50 of 5 μM.
in vivo: BMS-345541 effectively inhibits melanoma tumor growth in a dose-dependent manner. Tumor-bearing mice treated with 75 mg/kg of BMS-345541 shows effective inhibition of growth of SK-MEL-5, A375, and Hs 294T tumors by 86 %, 69% and 67%, respectively, when compared with control animals treated with vehicle alone.
For research only, not for human use!
没有评论:
发表评论