ACHP Hydrochloride (Compound 4j) exhibits potent IKK-β inhibitory (IC50: 8.5 nM) and cellular activities (IC50=40 nM, in A549 cells). ACHP moderately inhibits IKK-α with an IC50 of 250 nM but exhibits good selectivity towards other kinases, such as IKK3, Syk and MKK4 (IC50>20,000 nM). Moreover, ACHP demonstrates quite potent activity in various cellular assays. ACHP inhibits NF-κB-dependent reporter gene activation in TNFα-activated HEK293 cells and PMA/calcium ionophore-activated Jurkat T cells. ACHP fails to inhibit PMA-induced AP-1 activation in MRC-5 cells and PMA/calcium ionophore induced NF-κB dependent reporter gene transcription in Jurkat cells even at concentrations exceeding 10 μM. ACHP selectively interferes with the NF-κB signaling cascade by inhibition of IKK-β in living cells. ACHP inhibits the growth of these cells in a dose-dependent manner. Tax-active cell lines are more susceptible to ACHP than Tax-inactive cell lines and Jurkat (IC50 values in Tax-active cell lines, Tax-inactive cell lines or Jurkat are 3.1±1.3?μM, 10.7±1.7?μM and 23.6?μM, respectively), suggesting that the growth of Tax-active cells depends on NF-κB more than Tax-inactive cells.
Medlife has not independently confirmed the accuracy of these methods. They are for reference only.