MRS-4203

MRS-4203 is a novel small molecule, conformationally constrained (S)-methanocarba-7-deazaadenosine analogue that acts as a potent inhibitor of adenosine kinase (ADK), with a particular focus on the nuclear long isoform (ADK-L). Developed through a structure-based design approach by researchers at the National Institutes of Health (NIH) and Rutgers University, MRS-4203 selectively targets ADK-L to prevent epileptogenesis and posttraumatic epilepsy (PTE) by modulating DNA methylation levels. By blocking ADK-L, MRS-4203 prevents the clearance of nuclear adenosine, which shifts the transmethylation pathway equilibrium to increase S-adenosylhomocysteine (SAH) levels, subsequently inhibiting DNA methyltransferases (DNMTs) and reducing global DNA hypermethylation. In preclinical rodent models of temporal lobe epilepsy and controlled cortical impact-induced traumatic brain injury, transient systemic administration of MRS-4203 significantly reduced seizure frequency, duration, and brain excitability without causing the typical adverse effects associated with cytoplasmic ADK-S inhibition.

Other names

1962174-21-5MRS 4203MRS4203MRS-4203