CID-2858522

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

CID-2858522 是一种有效且特异性的抗原受体介导的 NF-κB 激活抑制剂 (IC50: 70 nM)。

CID-2858522 is an effective and specific antigen receptor-mediated NF-κB activation inhibitor (IC50: 70 nM).(In Vitro):CID-2858522 (Compound 1) also inhibits testosterone hydroxylase in the presence of human liver microsomes and an NADPH generating system (IC50: 85 μM) . In the HEK293 cell line, CID-2858522 suppresses NF-κB reporter gene activity in a concentration-dependent manner, with IC50 ~70 nM and with maximum inhibition achieved at 0.25-0.5 μM. In contrast, CID-2858522 does not inhibit TNF-induced NF-κB-reporter gene activity at concentrations as high as 4 μM. CID-2858522 also potently inhibits PMA/Ionomycin-induced NF-κB reporter gene activity in transient transfection assays .(In Vivo):CID-2858522 exhibits nonlinear pharmacokinetics, showing higher serum levels at the 0.5 h measurement time for the 30 mg/kg dose compared to 50 mg/kg but displaying typical dose-dependent behavior when measured at t=3 h. The increasing accumulation seen at a dose of 50 mg/kg may be due to a depot effect created by CYP3A4 inhibition. The cohort exhibits clear signs of morbidity at t=3 h at the 50 mg/kg dose .

CID-2858522 (Compound 1) inhibits antigen receptor-mediated NF-κB with an IC50 of 70 nM. CID-2858522 also inhibits testosterone hydroxylase in the presence of human liver microsomes (HLM) and an NADPH generating system with an IC50 of 85 μM. In the HEK293 cell line used for primary screening, CID-2858522 suppresses NF-κB reporter gene activity in a concentration-dependent manner, with IC50 ~70 nM and with maximum inhibition achieved at 0.25-0.5 μM. In contrast, CID-2858522 does not inhibit TNF-induced NF-κB-reporter gene activity at concentrations as high as 4 μM, thus demonstrating selectivity for the NF-κB pathway activated by PMA/Ionomycin. Cell viability assays indicate that CID-2858522 is not toxic to HEK293 cells at concentrations ≤8 μM. CID-2858522 also potently inhibits PMA/Ionomycin-induced NF-κB reporter gene activity in transient transfection assays.

In vivo dose-exposure profiling of CID-2858522(Compound 1a) is conducted using a small cohort of three male mice. CID-2858522 exhibits nonlinear pharmacokinetics, showing higher serum levels at the 0.5 h measurement time for the 30 mg/kg dose compared to 50 mg/kg but displaying typical dose-dependent behavior when measured at t=3 h. The increasing accumulation seen at a dose of 50 mg/kg may be due to a depot effect created by CYP3A4 inhibition. The cohort exhibits clear signs of morbidity at t=3 h at the 50 mg/kg dose.

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Apoptosis

NF-κB

NF-κB

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758679-97-9

465.638

C28H39N3O3

>98% (HPLC)

In Vitro:?DMSO : 25 mg/mL (53.69 mM)

Cc1cc2nc(NCCCO)n(CC(=O)c3cc(c(O)c(c3)C(C)(C)C)C(C)(C)C)c2cc1C

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(-20℃)

With Ice Pack

≥ 2 years