PS-1145

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种特异性 IκB 激酶 (IKK) 抑制剂，IC50 为 88 nM。

A specific IκB kinase (IKK) inhibitor with IC50 of 88 nM; shows no activity for JNK2, c-Src, p38α, IRAK, Lck, etc.; blocks TNFα-induced NF-κB activation in MM cells through inhibition of IκBα phosphorylation and degradation of IκBα, respectively; blocks the protective effect of IL-6 against Dex-induced apotosis, inhibits both IL-6 secretion from BMSCs triggered by MM cell adhesion and proliferation of MM cells adherent to BMSCs.

PS-1145 blocks TNFα-induced NF-κB activation in a dose- and time-dependent fashion in MM cells through inhibition of IκBα phosphorylation. Dexamethasone (Dex), which up-regulates IκBα protein, enhances blockade of NF-κB activation by PS-1145. PS-1145 blocks the protective effect of IL-6 against Dex-induced apotosis. TNFα-induced intracellular adhesion molecule (ICAM)-1 expression on both RPMI8226 and MM.1S cells is also inhibited by PS-1145. Moreover, PS-1145 inhibits both IL-6 secretion from bone marrow stromal cells (BMSCs)triggered by MM cell adhesion and proliferation of MM cells adherent to BMSCs.

Administration of either Bortezomib or PS-1145 (50 mg/kg) results in a significant decrease in serum levels of all 3 cytokines that is nonsignificantly different from those in mice that underwent transplantation with TCD BM alone. PS1145 is injectedintracerebroventricular (icv)as a pretreatment to block hypothalamic inflammation induced by IL-4 in adult male Wistar rats consuming a high-fat diet (HFD) over an 11-day period. The four groups of rats according to icv pretreatment/treatment condition are Veh/Veh, Veh/IL-4, PS1145/Veh, and PS1145/IL-4. Rats in the Veh/IL-4 group display increased weight gain on the HFD compared with the Veh/Veh group (P<0.05 on days 6-9).Importantly, the effect of icv IL-4 administration to increase body fat mass during high-fat (HF)feeding is completely blocked by icv PS1145 pretreatment at a dose that has no independent effect on body composition (on day 8: P<0.001, PS1145/Veh vs. PS1145/IL-4; P=not significant, PS1145/Veh vs. Veh/Veh).In PS1145/IL-4 injected rats, IL-1β mRNA content is decreased by ~75% compared with that of Veh/IL-4-injected rats.

PS1145 | PS 1145

Immunology/Inflammation

IκB kinase (IKK)

IKK

Inflammation/Immunology

——

431898-65-6

322.7484

C17H11ClN4O

>98% (HPLC)

DMSO: ≥ 43 mg/mL

C1=CC(=CN=C1)C(=O)NC2=CC(=CC3=C2NC4=C3C=CN=C4)Cl

3-Pyridinecarboxamide, N-(6-chloro-9H-pyrido[3,4-b]indol-8-yl)-

(-20℃)

With Ice Pack

≥ 2 years