cGMP-8-T-(EO)₅-ET-8-cGMP

Polymer-linked dimeric (PLD) cGMP analogue in which two cGMP units are linked by a spacer with 5 ethylene oxide units via thioethers at the C8 positions. Membrane-permeant cGMP dimer with enhanced PKG activation properties by addressing two binding sites simultaneously with a single molecule.
Activation constants of cGMP-8-T-(EO)₅-ET-8-cGMP in vitro on purified cGMP-dependent protein kinase (PKG) isozymes were measured to be in the range of < 1 nM (PKG1β and PKG2) and < 0.8 nM (PKG1α), respectively. The compound significantly reduced proliferation and migration combined with increased cell death in two melanoma cell lines. In the colon cancer cell line HT-29, treatment with cGMP-8-T-(EO)₅-ET-8-cGMP led to a significant reduction of cell viability.