ACHP Hydrochloride

Research use only, not for human use.

ACHP Hydrochloride (IKK-2 Inhibitor VIII) is a highly potent and selective IKK-β inhibitor (IC50: 8.5 nM).

ACHP Hydrochloride (IKK-2 Inhibitor VIII) is a highly potent and selective IKK-β inhibitor (IC50: 8.5 nM).

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.

ACHP (Compound 4j) is orally bioavailable in mice and rats and demonstrates significant in vivo activity in anti-inflammatory models (arachidonic acid-induced mouse ear edema model). ACHP has reasonable aqueous solubility (0.12 mg/mL in pH 7.4 isotonic buffer) and excellent Caco-2 permeability (Papp 62.3×10-7 cm/s), and demonstrates orally bioavailability in mice (BA: 16%) and rats (BA: 60%). The favourable bioavailability of ACHP in rats is likely due to its low clearance (0.33 L/h/kg). In an acute inflammation model, ACHP exhibits oral efficacy at 1 mg/kg in a dose-dependent manner.

IKK-2 Inhibitor VIII

Others

Other Targets

IKKα|IKKβ

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406209-26-5

400.9

C21H25ClN4O2

>98% (HPLC)

DMSO:45 mg/mL (112.25 mM; Need ultrasonic)

N#CC1=C(C=C(N=C1N)C2=C(C=CC=C2OCC3CC3)O)C4CCNCC4.[H]Cl

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(-20℃)

With Ice Pack

≥ 2 years