ICCB-19 hydrochloride is a TRADD (TNFRSF1A associated via death domain) inhibitor. It binds to the N-terminal domain of TRADD (TRADD-N), disrupting its interaction with both TRADD-C and TRAF2. ICCB-19 hydrochloride indirectly inhibits RIPK1 kinase activity, effectively inducing autophagy and the degradation of long-lived proteins[1].
体内研究
ICCB-19 diminishes inflammatory responses in Tradd mice by reducing the expression of TNF-induced inflammatory target gene products, NOS, and COXII27, as well as inflammatory cytokines in cells stimulated with pathogen-associated molecular patterns[1].
体外研究
ICCB-19 inhibits Bortezomib-induced apoptosis and RIPK1-dependent apoptosis (RDA) with an IC50 of approximately 1 μM[1].
ICCB-19 has no effect on mTOR. Treatment with ICCB-19 (10 μM) increases the levels of DsRed-FYVE dots and the lipid kinase activity of VPS34[1].
ICCB-19 (10 μM) induces autophagy by facilitating K63-linked ubiquitination of beclin 1 through the action of E3 ubiquitin ligases cIAP1 and cIAP2, along with the adaptor protein TRAF2[1].
ICCB-19 (10 μM) attenuates the rapid activation of RIPK1 in TNF-induced complex I. ICCB-19 treatment enhances the recruitment of TRADD, HOIP, and A20 to complex I, while not affecting RIPK1[1].
ICCB-19 HCl/盐酸ICCB-19 细胞实验
Cell Line
Concentration
Treated Time
Description
References
mouse primary chondrocytes
5 μM and 10 μM
24 hours
ICCB-19 partially restored the altered morphology of chondrocytes caused by TNF-α and inhibited the activation of RIPK1-TAK1-NF-κB signaling pathway
Cell Death Discov. 2023 Mar 31;9(1):109
ICCB-19 HCl/盐酸ICCB-19 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
DMM surgery-induced osteoarthritis model
Intra-articular injection
1 mg/kg
Twice a week for seven weeks
ICCB-19 significantly attenuated cartilage degeneration in DMM mice, reduced OARSI score, and restored the expression of COL2A1 and LC3
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