K-7174, 1,4-Bis[5-(3,4,5-triMethoxyphenyl)-4(E)-pentenyl]hexahydro-1H-1,4-diazepine

Uses

K-7174, a GATA-specific inhibitor, is a putative antiinflammatory agent that attenuates effects of inflammatory cytokines in certain cell types.

Biological Activity

K-7174 is a homopiperazine with dual GATA and proteasome inhibitory activtiy. K-7174 selective inhibts GATA-mediated gene regulations in cultures (10-30 μM; VCAM-1 expression in HUVECs or Epo suppression in Hep3B cells) and in vivo (30 mg/kg in mice via i.p. against IL-1beta- or TNF-alpha-induced anemia). K-7174 exhibits anti-myeloma activity in vitro (10-25 μM) and in vivo (50 mg/kg/day p.o. in mice) by targeting the active pockets of β1, β2 and β5 subunits of proteasome along hydrophobic grooves in the direction of the β7, β1 and β4 subunits in a manner distinct from th at of bortezomib.

in vivo