BI-D1870 Chemische Eigenschaften,Einsatz,Produktion Methoden
Verwenden
The 90 kDa ribosomal S6 kinases (RSKs) are a group of serine/threonine kinases involved in diverse cellular processes, including growth, survival, and motility. BI-D1870 is a cell permeable, ATP-competitive inhibitor of the four vertebrate isoforms of RSK, RSK1-4 (IC50s = 31, 24, 18, and 15 nM, respectively). At 100 nM, it also significantly inhibits polo-like kinase 1, Aurora B, maternal embryonic leucine zipper kinase, and mammalian STE20-like kinase 2. BI-D1870 acts at the N-terminal kinase domain, but not the C-terminal domain, of RSK.
Enzyminhibitor
This cell-permeant, ATP-competitive inhibitor (FW = 391.42 g/mol; CAS
501437-28-1: Solubility = 78 mg/mL DMSO; <1 mg/mL H2O), also known
as 2-[ (3,5-difluoro-4-hydroxyphenyl) amino]-7,8-dihydro-5,7-dimethyl-8- (3-
methylbutyl) -6 (5H) -pteridinone, targets the p90 Ribosomal protein S6
Kinase a-1, 2, 3, and 4, or RSK1, RSK2, RSK3, and RSK4, with IC50 values
of 31 nM, 24 nM, 18 nM, and 15 nM, respectively. RSK isoforms are
activated by Extracellular-signal-Regulated Kinases ERK1 and ERK2 in
response to growth factors, phorbol esters and other agonists. BI-D1870
shows 10x to 100x selectivity for RSK over MST2, GSK-3β, MARK3, CK1
and Aurora B protein kinases. When tested in vitro, BI-D1870 exhibits IC50
values for inhibits RSK1, RSK2, RSK3 and RSK4 are in the 10–30 nM.
Although assumed to be a remarkably specific inhibitor of RSK isoforms,
with a >500-fold greater selectivity over nine other AGC kinases, later work
assessing the ability of BI-D1870 to protect enzyme active sites from
alkylation demonstrated that several other kinases interact with BI-D1870
. Subsequent direct activity assays confirmed that Slk, Lok and Mst1
protein kinases are inhibited by BI-D1870 and that phosphorylation of some
of their substrates is blocked by BI-D1870 in living cells. Such results
suggest that the specificity of BI-D1870 cannot be taken for certain.
BI-D1870 Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
