KW-6356 – (858979-50-7)

Sipagladenant, also known by its developmental code name KW-6356, is an orally active adenosine A2A receptor inverse agonist developed by Kyowa Kirin. It is primarily investigated for its potential in treating frontal lobe dysfunction and has shown promise in improving cognitive impairment, alternation behavior, and gait parameters in preclinical studies.

Unlike istradefylline, a first-generation adenosine A2A receptor antagonist, sipagladenant demonstrates insurmountable antagonism and inverse agonism, which may confer distinct clinical advantages. The structural basis for its antagonistic properties has been elucidated through cocrystal structures of the A2A receptor in complex with sipagladenant, revealing critical interactions with residues such as His250 and Trp246.

These characteristics suggest that sipagladenant could offer improved therapeutic benefits compared to existing treatments, particularly in conditions where adenosine A2A receptor modulation is beneficial.

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Sources:

https://pubchem.ncbi.nlm.nih.gov/compound/23144148
https://www.medchemexpress.com/sipagladenant.html
https://www.medkoo.com/products/51896
https://www.sciencedirect.com/science/article/pii/S1353802023009860
https://pubmed.ncbi.nlm.nih.gov/36894319/