BLINK11 is a blood-brain barrier-permeable inhibitor of Cdk5. It reduces the activity of CDK5 by targeting CDK5/p35 (IC50 = 17.09 nM) and CDK5/p25 (IC50 = 14.69 nM) complexes. BLINK11 exhibits antidiabetic and neuroprotective properties, lowers blood glucose levels in type 2 diabetes (T2D) mice, enhances cognitive function, and reduces neurodegenerative lesions.

CDK5-p35:17.09 nM

BLINK11, when administered at concentrations of 50 nM to 100 nM for 24 hours, reduces CDK5 activity in CDK5/p35 (IC50 = 17.09 nM) and CDK5/p25 (IC50 = 14.69 nM) complexes. In N2A cell lines overexpressing CDK5/p35 and CDK5/p25, BLINK11 decreases CDK5 activity under the same conditions. Furthermore, BLINK11 at 100-500 μM for 7 hours demonstrates the ability to cross the blood-brain barrier (BBB) and access the central nervous system. When tested across HEK293T, HepG2, and N2A cell lines, BLINK11 maintains over 50% cell viability at concentrations ranging from 25-500μM for 24 hours.

BLINK11 (administered at 20-40 mg/kg/day, i.p., for 20 days) has demonstrated efficacy in alleviating symptoms associated with type 2 diabetes in a mouse model fed a high-fat diet (HFD).