TPCA-1

TPCA-1 (507475-17-4) selective inhibitor of IκB kinase 2 (IKK2) (IC₅₀ = 17.9 nM).¹ Inhibits production of pro-inflammatory cytokines in arthritis and other animal models of inflammation.^1,2 Also attenuates NLRP3 inflammasome activation in THP-1 myeloid cells, and suppresses IL1β-induced proliferation, migration, and invasion of HeLa cells.^3,4 Continuous exposure to TPCA-1 promotes expansion of hematopoietic stem/progenitor cells (HSPCs) via improved glycolysis and limited ROS production.⁵

References/Citations:

1. Podolin et al. (2005), Attenuation of murine collagen-induced arthritis by a novel, selective small molecule inhibitor of IkappaB Kinase 2, TPCA-1 (2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide), occurs via reduction of proinflammatory cytokines and antigen-induced T cell Proliferation; Pharmacol. Exp. Ther., 312 373
2. Wang et al. (2021), TPCA-1 negatively regulates inflammation mediated by NF-kB pathway in mouse chronic periodontitis model; Oral Microbiol., 36 192
3. Unterreiner et al. (2021), Pharmacological inhibition of IKKb dampens NLRP3 inflammasome activation after priming in the human myeloid cell line THP-1; Biophys. Res. Commun., 545 177
4. Tao et al. (2021), IL-1b promotes cervical cancer though activating NF-κB/CCL-2; J. Exp. Pathol., 14 426
5. Sun et al. (2021), Continuous NF-κB pathway inhibition promotes expansion of human phenotypical hematopoietic stem/progenitor cells through metabolism regulation; Cell Res., 399 112468