Chemistry:Sipagladenant
Sipagladenant (INN; developmental code name KW-6356) 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.[1][2][3][4] It reached phase 2 clinical trials prior to the discontinuation of its development in 2022.[1][2]
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.[4]
The metabolism of KW-6356 generates M6, an active metabolite with similar potency as a A2A antagonist/inverse agonist.[4]
Pharmacokinetics
The half-life of KW-6356 is 22.9 hours. The half-life of M6 is 4.34 hours.[4]
Development
Kyowa Kirin halted development of KW-6356 in 2022 based on regulatory and developmental challenges surrounding the drug.[5]
See also
- List of investigational Parkinson's disease drugs
References
- ↑ 1.0 1.1 "Sipagladenant". 5 November 2023. https://adisinsight.springer.com/drugs/800048106.
- ↑ 2.0 2.1 "Delving into the Latest Updates on KW-6356 with Synapse". 24 January 2026. https://synapse.patsnap.com/drug/e6a3c1c95507492d8661cd05789ca96d.
- ↑ "Randomized controlled trial of KW-6356 monotherapy in patients with early untreated Parkinson's disease" (in English). Parkinsonism & Related Disorders 117. December 2023. doi:10.1016/j.parkreldis.2023.105907. PMID 37948832.
- ↑ 4.0 4.1 4.2 4.3 "In Vitro Pharmacological Profile of KW-6356, a Novel Adenosine A2A Receptor Antagonist/Inverse Agonist". Molecular Pharmacology 103 (6): 311–324. June 2023. doi:10.1124/molpharm.122.000633. PMID 36894319.
- ↑ "Kyowa Kirin Announced Discontinuation of KW-6356". https://www.kyowakirin.com/media_center/news_releases/2022/pdf/e20220715_01.pdf.
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