cGMP-8-TMAmd-(PEG pd 2000)-AmdMT-8-cGMP

Polymer-linked dimeric (PLD) cGMP analogue in which two cGMP units are linked by a polydisperse 2000 Dalton spacer on basis of polyethylene glycol (PEG) 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-TMAmd-(PEG pd 2000)-AmdMT-8-cGMP in vitro on purified cGMP-dependent protein kinase (PKG) isozymes were measured to be in the range of 7.7 ± 1.3 nM (PKG1α), 21 ± 2 nM (PKG1β), and 2.1 ± 0.6 nM (PKG2), respectively. The compound significantly reduced proliferation, migration and increased cell death in two melanoma cell lines. In the colon cancer cell lines Caco-2 and HCT 116, treatment with cGMP-8-TMAmd-(PEG pd 2000)-AmdMT-8-cGMP led to a significant reduction of cell viability.