K-7174 (hydrochloride)

K-7174 is a 20S proteasome inhibitor.¹ It inhibits the β1, β2, and β5 catalytic subunits of the 20S proteasome when used at a concentration of 5 µM. K-7174 (10 µM) reduces TNF-α- or IL-1β-induced adherence of U937 monocytes to human umbilical vein endothelial cells (HUVECs) in a co-culture model of monocyte-endothelial cell adhesion.² It inhibits tumor growth in U266 and RPMI-8226 multiple myeloma mouse xenograft models when administered at a dose of 75 mg/kg.³ K-7174 also inhibits the GATA consensus sequence, reducing TNF-α-induced binding of HUVEC nuclear extracts to GATA motifs in the VCAM1 promoter in an EMSA when used at a concentration of 30 µM.^4,2

WARNING This product is not for human or veterinary use.

1. Kikuchi, J., Shibayama, N., Yamada, S., et al. Homopiperazine derivatives as a novel class of proteasome inhibitors with a unique mode of proteasome binding. PLoS One 8(4), e60649 (2013).

2. Umetani, M., Nakao, H., Doi, T., et al. A novel cell adhesion inhibitor, K^-7174, reduces the endothelial VCAM-1 induction by inflammatory cytokines, acting through the regulation of GATA. Biochem. Biophys. Res. Commun. 272(2), 370-374 (2000).

3. Kikuchi, J., Yamada, S., Koyama, D., et al. The novel orally active proteasome inhibitor K^-7174 exerts anti-myeloma activity in vitro and in vivo by down-regulating the expression of class I histone deacetylases. The Journal of Biological Chemisty 288(35), 25593-25602 (2013).

4. Imagawa, S., Nakano, Y., Obara, N., et al. A GATA-specific inhibitor (K^-7174) rescues anemia induced by IL-1β, TNF-α, or L-NMMA. The FASEB Journal 17(12), 1742-1744 (2003).