KW-6356

KW-6356 is a non-xanthine selective A_2A adenosine antagonist/inverse agonist that was previously under development by Kyowa Kirin as a monotherapy and adjunctive treatment to levodopa therapy in Parkinsonism. ^[1]

Pharmacology

Pharmacodynamics

KW-6356 is a selective A_2A adenosine antagonist/inverse agonist displaying insurmountable antagonism of this adenosine subtype. Compared to the first generation A_2A adenosine inverse agonist Istradefylline, KW-6356 possesses a 100-fold greater affinity for the A_2A adenosine receptor and dissociates more slowly from the receptor. ^[2]

The metabolism of KW-6356 generates M6, an active metabolite with similar potency as a A_2A antagonist/inverse agonist. ^[2]

Pharmacokinetics

The half-life of KW-6356 is 22.9 hours. The half-life of M6 is 4.34 hours. ^[2]

Development

On July 15th, 2022 Kyowa Kirin announced that development of KW-6356 would be halted following a thorough evaluation of regulatory and developmental challenges surrounding the drug. ^[3]

References

1. Maeda, Tetsuya; Kimura, Takashi; Sugiyama, Kenichiro; Yamada, Kana; Hiraiwa, Ren; Nishi, Masato; Hattori, Nobutaka; Abe, Takashi; Deguchi, Kentaro; Fujimoto, Kenichi; Hasegawa, Kazuko; Hatsuta, Hiroyuki; Hattori, Nobutaka; Hattori, Tatsuya; Ikebe, Shinichiro (2023-12-01). "Randomized controlled trial of KW-6356 monotherapy in patients with early untreated Parkinson's disease". Parkinsonism & Related Disorders. 117. doi:10.1016/j.parkreldis.2023.105907. ISSN   1353-8020. PMID   37948832.
2. Ohno, Yutaro; Suzuki, Michihiko; Asada, Hidetsugu; Kanda, Tomoyuki; Saki, Mayumi; Miyagi, Hikaru; Yasunaga, Mai; Suno, Chiyo; Iwata, So; Saito, Jun-ichi; Uchida, Shinichi (2023-06-01). "In Vitro Pharmacological Profile of KW-6356, a Novel Adenosine A2A Receptor Antagonist/Inverse Agonist". Molecular Pharmacology. 103 (6): 311–324. doi:10.1124/molpharm.122.000633. ISSN   0026-895X.
3. "Kyowa Kirin Announced Discontinuation of KW-6356" (PDF).