ACHP Hydrochloride demonstrates strong inhibition of IKK-β (IC50: 8.5 nM) and shows cellular efficacy (IC50=40 nM in A549 cells). It inhibits IKK-α moderately with an IC50 of 250 nM and maintains high selectivity against other kinases, such as IKK3, Syk, and MKK4 (IC50>20,000 nM). Additionally, ACHP exhibits significant effectiveness in various cell-based assays. It blocks NF-κB-dependent reporter gene activity in TNFα-stimulated HEK293 cells and PMA/calcium ionophore-activated Jurkat T cells. However, ACHP does not inhibit PMA-induced AP-1 activation in MRC-5 cells or PMA/calcium ionophore-induced NF-κB-dependent reporter gene expression in Jurkat cells at doses above 10 μM. ACHP specifically disrupts NF-κB signaling by targeting IKK-β in live cells[1]. ACHP reduces cell proliferation in a dose-responsive manner. Cell lines active for Tax show greater sensitivity to ACHP compared to Tax-inactive cell lines and Jurkat cells (with IC50 values of 3.1±1.3 μM for Tax-active cell lines, 10.7±1.7 μM for Tax-inactive cell lines, and 23.6 μM for Jurkat, respectively), indicating a higher reliance on NF-κB for the growth of Tax-active cells than for Tax-inactive cells[2].
体内研究
ACHP possesses oral bioavailability in both mice and rats, showing notable in vivo efficacy in models of inflammation (such as the arachidonic acid-induced mouse ear edema model). It has adequate water solubility (0.12 mg/mL in pH 7.4 isotonic buffer) and outstanding Caco-2 permeability (Papp 62.3×10^-7 cm/s), with oral bioavailability observed in mice (BA: 16%) and rats (BA: 60%). The improved bioavailability in rats is attributed to its low clearance rate (0.33 L/h/kg). ACHP is orally effective at a dose of 1 mg/kg, demonstrating dose-dependent activity in acute inflammation models[1].
体外研究
ACHP Hydrochloride demonstrates strong inhibition of IKK-β (IC50: 8.5 nM) and shows cellular efficacy (IC50=40 nM in A549 cells). It inhibits IKK-α moderately with an IC50 of 250 nM and maintains high selectivity against other kinases, such as IKK3, Syk, and MKK4 (IC50>20,000 nM). Additionally, ACHP exhibits significant effectiveness in various cell-based assays. It blocks NF-κB-dependent reporter gene activity in TNFα-stimulated HEK293 cells and PMA/calcium ionophore-activated Jurkat T cells. However, ACHP does not inhibit PMA-induced AP-1 activation in MRC-5 cells or PMA/calcium ionophore-induced NF-κB-dependent reporter gene expression in Jurkat cells at doses above 10 μM. ACHP specifically disrupts NF-κB signaling by targeting IKK-β in live cells[1].
ACHP reduces cell proliferation in a dose-responsive manner. Cell lines active for Tax show greater sensitivity to ACHP compared to Tax-inactive cell lines and Jurkat cells (with IC50 values of 3.1±1.3 μM for Tax-active cell lines, 10.7±1.7 μM for Tax-inactive cell lines, and 23.6 μM for Jurkat, respectively), indicating a higher reliance on NF-κB for the growth of Tax-active cells than for Tax-inactive cells[2].
ACHP HCl 细胞实验
Cell Line
Concentration
Treated Time
Description
References
human keratinocytes
2.5 μM
30 min
Inhibited NF-κB signaling pathway, reduced induction of CXCL8, CXCL1, and CXCL2
J Invest Dermatol. 2019 Jul;139(7):1506-1515. e7
mouse keratinocytes
2.5 μM
30 min
Inhibited NF-κB signaling pathway, prevented IκBα degradation, and reduced induction of pro-inflammatory cytokines and chemokines
J Invest Dermatol. 2019 Jul;139(7):1506-1515. e7
Human adult lung fibroblasts (HLFa)
50 μM
24 h
To investigate the inhibitory effect of ACHP on TGF-β1-induced fibroblast-to-myofibroblast transition. Results showed that ACHP significantly suppressed the expression of αSMA and SM22α, as well as the deposition of collagen type I and fibronectin.
J Cell Mol Med. 2015 Dec;19(12):2780-92
HEL 299 cells
1-30 µM
24 h
Concentration-dependent reduction in cell viability
Biomolecules. 2019 Dec 13;9(12):875
H1299 cells
10 µM
4 h
Inhibited IL-6-induced STAT3 activation, reduced phosphorylation of upstream kinases JAK1, JAK2, and Src
Biomolecules. 2019 Dec 13;9(12):875
A549 cells
10 µM
4 h
Inhibited STAT3 phosphorylation, reduced STAT3 nuclear translocation and DNA binding ability
Biomolecules. 2019 Dec 13;9(12):875
human dendritic cells
500 nM
24 h
Inhibition of NF-κB signaling pathway, significantly inhibited IDO1 biosynthesis
PLoS One. 2015 Feb 25;10(2):e0118562
OM10.1 cells
0.56 μM
24 h
To evaluate the inhibitory effect of ACHP on TNF-α-induced HIV-1 replication. Results showed that ACHP significantly inhibited the increase in HIV p24 antigen levels, with an EC50 of approximately 0.56 μM.
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