N-[4-[5-(1,3-BENZODIOXOL-5-YL)-3-METHOXY-1H-1,2,4-TRIAZOL-1-YL]PHENYL]-2-(PHENYLTHIO)ACETAMIDE

SecinH3 is a Sec7 cytohesin inhibitor.

A cell-permeable triazolo compound that acts as a Sec7 domain-binding (K_d ≤250 nM for Sec7 from human cytohesins 1-3), selective antagonist against cytohesin family small GEFs (IC₅₀ ≤5.6 μM in ARF1 GDP/GTP exchange assays using human cytohesin 3, as well as murine and Drosophila homologues). It inhibits large GEFs only at much higher concentrations (IC₅₀ ≥65 μM in GDP/GTP exchange assays using hEFA6-S7 and yGea2-S7) and exhibits little activity against a panel of 10 commonly studied kinases or hSosII. Shown to effectively inhibit insulin signaling both in HepG2 cells in vitro and in Drosophila and mice in vivo.

Sec7-specific GEF inhibitor that displays selectivity for small GEFs of the cytohesin family (IC 50 values are 2.4, 5.4, 5.4, 5.6, 5.6, 65 and > 100 μ M for hCyh2, hCyh1, mCyh3, hCyh3, drosophila steppke, yGea2-S7 and hEFA6-S7 respectively). Inhibits insulin signaling via inhibition of insulin receptor substrate protein (IRS) phosphorylation.