SP100030 | Dual NF-kB/AP-1 inhibitor

SP100030 (154563-54-9) is a potent dual inhibitor of NF-kB- and AP-1-mediated gene expression (IC_50’s = 50 nM for both in transfected Jurkat T-cells).¹ It was able to specifically block IL-2 and IL-8 in Jurkat T-cells (IC_50’s = 30 nM for both).¹ SP100030 treatment significantly decreased arthritis severity in DBA/1J mice.² It selectively inhibited CD8(+) T-cells and mRNA expression of TH1 and Th2 cytokines in a rat model of asthma but did not inhibit allergen-induced eosinophilia and bronchial hyperresponsiveness.³ SP100030 ameliorated muscle wasting in a cancer cachexia rat model.⁴ SP100030 suppression of T cell activation has been attributed to targeting of XPO1 (with minimal impact on nuclear export and cell viability).⁵

References/Citations:

1. Sullivan et al. (1998), 2-Chloro-4-(trifluoromethyl)pyrimidine-5-N-(3’,5’-bis(trifluoromethyl)phenyl)carboxamide: A Potent Inhibitor of NF-kB- and AP-1-Mediated Gene Expression Identified Using Solution-Phase Combinatorial Chemistry; J. Med. Chem. 41 413
2. Gerlag et al. (2000), The effect of a T cell-specific NF-kappa B inhibitor on in vitro cytokine production and collagen-induced arthritis; J. Immunol. 165 1652
3. Huang et al. (2001), A novel transcription factor inhibitor, SP100030, inhibits cytokine gene expression, but not airway eosinophilia or hyperresponsiveness in sensitized and allergen-exposed rats; Br. J. Pharmacol. 134 1029
4. Moore-Carrasco et al. (2007), The AP-1/NF-kappaB double inhibitor SP100030 can revert muscle wasting during experimental cancer cachexia; Int. J. Oncol. 30 1239
5. Chen et al. (2024), Targeting the chromatin binding of exportin-1 disrupts NFAT and T cell activation; Nat. Chem. Biol. 20 1260