Sipagladenant (; developmental code name KW-6356) is a non-xanthine selective antagonist or inverse agonist of the adenosine A<sub>2A</sub> 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.
KW-6356 is a selective A<sub>2A</sub> adenosine antagonist or inverse agonist displaying insurmountable antagonism of this adenosine subtype. Compared to the first generation A<sub>2A</sub> adenosine inverse agonist Istradefylline, KW-6356 possesses a 100-fold greater affinity for the A<sub>2A</sub> adenosine receptor and dissociates more slowly from the receptor.
The metabolism of KW-6356 generates M6, an active metabolite with similar potency as a A<sub>2A</sub> antagonist/inverse agonist.
The half-life of KW-6356 is 22.9 hours. The half-life of M6 is 4.34 hours.
Kyowa Kirin halted development of KW-6356 in 2022 based on regulatory and developmental challenges surrounding the drug.