KW-6356For research use only. Not for human consumption.

For In Vitro Research Use Only – Not for Human or Veterinary Application

KW-6356 (sipagladenant)

How it binds

KW-6356 is a selective ligand of the adenosine A2A receptor, with a reported pKi of 9.93 at the human receptor. It works two ways at once. It blocks adenosine (antagonism), and it pushes down the receptor's baseline activity (inverse agonism).

What sets it apart from Kyowa Kirin's earlier A2A antagonist, istradefylline, is how it lets go. KW-6356 dissociates from the receptor very slowly, and in vitro its antagonism is insurmountable: adding more agonist doesn't overcome it. Istradefylline's antagonism is surmountable. Co-crystal structures of both compounds bound to A2A point to residues His250 and Trp246, and to contacts at the "lid" of the binding pocket, as the reason. An active metabolite, M6, has also been described.

The published record

It is short and comes entirely from the developer and its collaborators: about six PubMed papers. They cover receptor pharmacology and crystallography, MPTP-treated common marmosets studied alone and alongside L-DOPA, and Phase 1 and Phase 2 clinical studies in Japan. Kyowa Kirin ended the programme on July 15, 2022, citing the regulatory landscape, development hurdles and timelines. It is not approved anywhere, and no independent groups have published on it.

This listing

30 capsules of 1 mg per bottle (size 1 HPMC capsules with microcrystalline cellulose). The certificate linked above is a NuMega Resonance Labs qNMR report showing 97.5%, dated July 16, 2024. It was commissioned by the manufacturer, not by us, and it says so on the page. We haven't yet run our own test on this lot (0726J).

References

• Ohno et al. 2023, binding kinetics and crystal structures: PMID 36894319
• Ohno et al. 2023, marmoset model: PMID 37146707, PMID 37257947
• Kyowa Kirin discontinuation notice, July 15, 2022: kyowakirin.com
• PubChem: CID 23144148

Disclaimer
This compound has not been evaluated by the FDA. It is not intended to diagnose, treat, cure, or prevent any disease. All use must follow institutional and regulatory guidelines.

Terms of Sale
By purchasing, the buyer affirms they are a qualified researcher or institution. All sales are final. The purchaser assumes full responsibility for handling, use, and regulatory compliance. KW-6356 reference material is supplied for qualified in vitro laboratory research only — not for human or veterinary consumption, administration, compounding, dispensing, diagnostic use, therapeutic use, or patient use.