Sipagladenant


Sipagladenant is a non-xanthine selective antagonist or inverse agonist of the adenosine A2A receptor that was previously under development by Kyowa Kirin as a monotherapy and adjunctive to levodopa therapy in Parkinsonism. It reached phase 2 clinical trials prior to the discontinuation of its development in 2022.

Pharmacology

Pharmacodynamics

KW-6356 is a selective A2A adenosine antagonist or inverse agonist displaying insurmountable antagonism of this adenosine subtype. Compared to the first generation A2A adenosine inverse agonist Istradefylline, KW-6356 possesses a 100-fold greater affinity for the A2A adenosine receptor and dissociates more slowly from the receptor.
The metabolism of KW-6356 generates M6, an active metabolite with similar potency as a A2A antagonist/inverse agonist.

Pharmacokinetics

The half-life of KW-6356 is 22.9 hours. The half-life of M6 is 4.34 hours.

Development

Kyowa Kirin halted development of KW-6356 in 2022 based on regulatory and developmental challenges surrounding the drug.