For research use only. Not for therapeutic Use.
CID-2858522 is a highly potent and selective antigen receptor-mediated NF-κB activation inhibitor with an IC50 of 70 nM.
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[1]. 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[2].
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[2].
| Catalog Number | I004809 |
| CAS Number | 758679-97-9 |
| Synonyms | 1-(3,5-ditert-butyl-4-hydroxyphenyl)-2-[2-(3-hydroxypropylamino)-5,6-dimethylbenzimidazol-1-yl]ethanone |
| Molecular Formula | C28H39N3O3 |
| Purity | ≥95% |
| InChI | InChI=1S/C28H39N3O3/c1-17-12-22-23(13-18(17)2)31(26(30-22)29-10-9-11-32)16-24(33)19-14-20(27(3,4)5)25(34)21(15-19)28(6,7)8/h12-15,32,34H,9-11,16H2,1-8H3,(H,29,30) |
| InChIKey | CYCGGKILBWERDJ-UHFFFAOYSA-N |
| SMILES | CC1=CC2=C(C=C1C)N(C(=N2)NCCCO)CC(=O)C3=CC(=C(C(=C3)C(C)(C)C)O)C(C)(C)C |
| Reference | [1]. Okolotowicz KJ, et al. Selective benzimidazole inhibitors of the antigen receptor-mediated NF-kappaB activationpathway. Bioorg Med Chem. 2010 Mar 1;18(5):1918-24. [2]. Peddibhotla S, et al. Inhibition of protein kinase C-driven nuclear factor-kappaB activation: synthesis, structure-activity relationship, and pharmacological profiling of pathway specific benzimidazole probe molecules. J Med Chem. 2010 Jun 24;53(12):4793- [3]. Shi R, et al. Chemical biology strategy reveals pathway-selective inhibitor of NF-kappaB activation induced by protein kinase C. ACS Chem Biol. 2010 Mar 19;5(3):287-99. |
