Luvadaxistat

Luvadaxistat
Clinical data
Other names	NBI-1065844; NBI1065844; TAK-831; TAK831
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name 6-[2-[4-(Trifluoromethyl)phenyl]ethyl]-1,2-dihydropyridazine-3,4-dione;
CAS Number	1425511-32-5;
PubChem CID	71270546;
DrugBank	DB16067;
ChemSpider	29419992;
UNII	76IC00YRVR;
KEGG	D11981;
ChEMBL	ChEMBL2338801;
Chemical and physical data
Formula	C13H11F3N2O2
Molar mass	284.238 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1=CC(=CC=C1CCC2=CC(=O)C(=O)NN2)C(F)(F)F;
	InChI InChI=1S/C13H11F3N2O2/c14-13(15,16)9-4-1-8(2-5-9)3-6-10-7-11(19)12(20)18-17-10/h1-2,4-5,7H,3,6H2,(H,17,19)(H,18,20); Key:QBQMUMMSYHUDFM-UHFFFAOYSA-N;

Luvadaxistat (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name; NBI-1065844, TAK-831) is an experimental drug that works as a D-amino acid oxidase (DAAO) inhibitor and is supposed to increase NMDA receptor functionality.^[1] It is developed to treat Friedrich ataxia^[2] and negative symptoms of schizophrenia.^[3]^[4]^[5] As of September 2024, it is in phase 2 clinical trials for schizophrenia, no recent development has been reported for ataxia, and the drug has been discontinued for Friedreich's ataxia.^[6]

References

^ O’Donnell, Patricio; Dong, Cheng; Murthy, Venkatesha; Asgharnejad, Mahnaz; Du, Xiaoming; Summerfelt, Ann; Lu, Hong; Xu, Lin; Wendland, Jens R.; Dunayevich, Eduardo; Buhl, Derek L.; Litman, Robert; Hetrick, William P.; Hong, L. Elliot; Rosen, Laura B. (June 2023). "The D-amino acid oxidase inhibitor luvadaxistat improves mismatch negativity in patients with schizophrenia in a randomized trial". Neuropsychopharmacology. 48 (7): 1052–1059. doi:10.1038/s41386-023-01560-0. ISSN 1740-634X. PMC 10018616. PMID 36928351.
^ Wang, Hao; Norton, Jonathan; Xu, Lin; DeMartinis, Nicholas; Sen, Rohini; Shah, Ankit; Farmer, Jennifer; Lynch, David (June 2021). "Results of a randomized double‐blind study evaluating luvadaxistat in adults with Friedreich ataxia". Annals of Clinical and Translational Neurology. 8 (6): 1343–1352. doi:10.1002/acn3.51373. PMC 8164851. PMID 34018342.
^ Fradley, Rosa; Goetghebeur, Pascal; Miller, David; Burley, Russell; Almond, Sarah; Gruart i Massó, Agnès; Delgado García, José M.; Zhu, Bin; Howley, Eimear; Neill, Jo C.; Grayson, Ben; Gaskin, Philip; Carlton, Mark; Gray, Ian; Serrats, Jordi; Davies, Ceri H. (October 2023). "Luvadaxistat: A Novel Potent and Selective d-Amino Acid Oxidase Inhibitor Improves Cognitive and Social Deficits in Rodent Models for Schizophrenia". Neurochemical Research. 48 (10): 3027–3041. doi:10.1007/s11064-023-03956-2. PMC 10471729. PMID 37289348.
^ Veselinović, Tanja; Neuner, Irene (August 2022). "Progress and Pitfalls in Developing Agents to Treat Neurocognitive Deficits Associated with Schizophrenia". CNS Drugs. 36 (8): 819–858. doi:10.1007/s40263-022-00935-z. PMC 9345797. PMID 35831706.
^ Kuo, Chien-Yi; Lin, Chieh-Hsin; Lane, Hsien-Yuan (November 2022). "Targeting d-Amino Acid Oxidase (DAAO) for the Treatment of Schizophrenia: Rationale and Current Status of Research". CNS Drugs. 36 (11): 1143–1153. doi:10.1007/s40263-022-00959-5. PMID 36194364. S2CID 252694226.
^ "Luvadaxistat". AdisInsight. 18 September 2024. Retrieved 4 November 2024.

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[1] O’Donnell, Patricio; Dong, Cheng; Murthy, Venkatesha; Asgharnejad, Mahnaz; Du, Xiaoming; Summerfelt, Ann; Lu, Hong; Xu, Lin; Wendland, Jens R.; Dunayevich, Eduardo; Buhl, Derek L.; Litman, Robert; Hetrick, William P.; Hong, L. Elliot; Rosen, Laura B. (June 2023). "The D-amino acid oxidase inhibitor luvadaxistat improves mismatch negativity in patients with schizophrenia in a randomized trial". Neuropsychopharmacology. 48 (7): 1052–1059. doi:10.1038/s41386-023-01560-0. ISSN 1740-634X. PMC 10018616. PMID 36928351.

[2] Wang, Hao; Norton, Jonathan; Xu, Lin; DeMartinis, Nicholas; Sen, Rohini; Shah, Ankit; Farmer, Jennifer; Lynch, David (June 2021). "Results of a randomized double‐blind study evaluating luvadaxistat in adults with Friedreich ataxia". Annals of Clinical and Translational Neurology. 8 (6): 1343–1352. doi:10.1002/acn3.51373. PMC 8164851. PMID 34018342.

[3] Fradley, Rosa; Goetghebeur, Pascal; Miller, David; Burley, Russell; Almond, Sarah; Gruart i Massó, Agnès; Delgado García, José M.; Zhu, Bin; Howley, Eimear; Neill, Jo C.; Grayson, Ben; Gaskin, Philip; Carlton, Mark; Gray, Ian; Serrats, Jordi; Davies, Ceri H. (October 2023). "Luvadaxistat: A Novel Potent and Selective d-Amino Acid Oxidase Inhibitor Improves Cognitive and Social Deficits in Rodent Models for Schizophrenia". Neurochemical Research. 48 (10): 3027–3041. doi:10.1007/s11064-023-03956-2. PMC 10471729. PMID 37289348.

[4] Veselinović, Tanja; Neuner, Irene (August 2022). "Progress and Pitfalls in Developing Agents to Treat Neurocognitive Deficits Associated with Schizophrenia". CNS Drugs. 36 (8): 819–858. doi:10.1007/s40263-022-00935-z. PMC 9345797. PMID 35831706.

[5] Kuo, Chien-Yi; Lin, Chieh-Hsin; Lane, Hsien-Yuan (November 2022). "Targeting d-Amino Acid Oxidase (DAAO) for the Treatment of Schizophrenia: Rationale and Current Status of Research". CNS Drugs. 36 (11): 1143–1153. doi:10.1007/s40263-022-00959-5. PMID 36194364. S2CID 252694226.

[AdisInsight-6] "Luvadaxistat". AdisInsight. 18 September 2024. Retrieved 4 November 2024.

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