Sipagladenant

Sipagladenant
Clinical data
Other namesKW-6356; KW6356
Routes of
administration		Oral[1]
Drug classAdenosine A2A receptor antagonist; Antiparkinsonian agent
ATC code
  • None
Pharmacokinetic data
Onset of action0.75–3 hours (TmaxTooltip time to peak levels)[2]
Elimination half-life18.4–43.1 hours[2]
Identifiers
  • N-(4-(furan-2-yl)-5-(tetrahydro-2H-pyran-4-carbonyl)thiazol-2-yl)-6-methylnicotinamide
CAS Number
PubChem CID
DrugBank
UNII
ChEMBL
PDB ligand
Chemical and physical data
FormulaC20H19N3O4S
Molar mass397.45 g·mol−1
3D model (JSmol)
  • CC1=NC=C(C=C1)C(=O)NC2=NC(=C(S2)C(=O)C3CCOCC3)C4=CC=CO4
  • InChI=InChI=1S/C20H19N3O4S/c1-12-4-5-14(11-21-12)19(25)23-20-22-16(15-3-2-8-27-15)18(28-20)17(24)13-6-9-26-10-7-13/h2-5,8,11,13H,6-7,9-10H2,1H3,(H,22,23,25)
  • Key:KMFLQPJJHQNKKF-UHFFFAOYSA-N

Sipagladenant (INNTooltip International Nonproprietary Name; 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][3][4][5] It reached phase 2 clinical trials prior to the discontinuation of its development in 2022.[1][3]

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.[5]

The metabolism of KW-6356 generates M6, an active metabolite with similar potency as a A2A antagonist/inverse agonist.[5]

Pharmacokinetics

The half-life of KW-6356 is 22.9 hours. The half-life of M6 is 4.34 hours.[5]

Development

Kyowa Kirin halted development of KW-6356 in 2022 based on regulatory and developmental challenges surrounding the drug.[6]

See also

References

  1. ^ a b c "Sipagladenant". AdisInsight. 5 November 2023. Retrieved 28 January 2026.
  2. ^ a b Tayama T, Ishiuchi M, Sugiyama K, Oka Y, Maeda H, Nagata Y, et al. (August 2023). "Safety, Tolerability, and Pharmacokinetics of the Novel Adenosine A2A Antagonist/Inverse Agonist KW-6356 Following Single and Multiple Oral Administration in Healthy Volunteers". Clin Pharmacol Drug Dev. 12 (8): 801–809. doi:10.1002/cpdd.1222. PMID 36683291.
  3. ^ a b "Delving into the Latest Updates on KW-6356 with Synapse". Synapse. 24 January 2026. Retrieved 28 January 2026.
  4. ^ Maeda T, Kimura T, Sugiyama K, Yamada K, Hiraiwa R, Nishi M, et al. (December 2023). "Randomized controlled trial of KW-6356 monotherapy in patients with early untreated Parkinson's disease". Parkinsonism & Related Disorders. 117 105907. doi:10.1016/j.parkreldis.2023.105907. PMID 37948832.
  5. ^ a b c d Ohno Y, Suzuki M, Asada H, Kanda T, Saki M, Miyagi H, et al. (June 2023). "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. PMID 36894319.
  6. ^ "Kyowa Kirin Announced Discontinuation of KW-6356" (PDF).
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