Zelatriazin Explained

Legal Status:	Investigational
Synonyms:	NBI-1065846; TAK-041
Cas Number:	1929519-13-0
Pubchem:	121349608
Iupac Name:	2-(4-Oxo-1,2,3-benzotriazin-3-yl)-N-[(1''S'')-1-[4-(trifluoromethoxy)phenyl]ethyl]acetamide
C:	18
H:	15
F:	3
N:	4
O:	3

Zelatriazin (NBI-1065846 or TAK-041) is a small-molecule agonist of GPR139. It was developed for schizophrenia and anhedonia in depression but trials were unsuccessful and its development was discontinued in 2023.^{[1] [2] [3] [4] [5] [6] [7]}

Notes and References

1. Kamel . Amin . Bowlin . Steve . Hosea . Natalie . Arkilo . Dimitrios . Laurenza . Antonio . In Vitro Metabolism of Slowly Cleared G Protein–Coupled Receptor 139 Agonist TAK-041 Using Rat, Dog, Monkey, and Human Hepatocyte Models (HepatoPac): Correlation with In Vivo Metabolism . Drug Metabolism and Disposition . February 2021 . 49 . 2 . 121–132 . 10.1124/dmd.120.000246. 33273044 . 227282766 . free .
2. Schiffer . Hans . Atienza . Josephine . Reichard . Holly . Mulligan . Victoria . Cilia . Jackie . Monenschein . Holger . Collia . Deanna . Ray . Jim . Kilpatrick . Gavin . Brice . Nicola . Carlton . Mark . Hitchcock . Steve . Corbett . Ged . Hodgson . Robert . S180. The Selective Gpr139 Agonist Tak-041 Reverses Anhedonia and Social Interaction Deficits in Rodent Models Related to Negative Symptoms in Schizophrenia . Schizophrenia Bulletin . 18 May 2020 . 46 . Supplement_1 . S106–S107 . 10.1093/schbul/sbaa031.246. free . 7234360 .
3. Yin . Wei . Han . David . Khudyakov . Polyna . Behrje . Rhett . Posener . Joel . Laurenza . Antonio . Arkilo . Dimitrios . A phase 1 study to evaluate the safety, tolerability and pharmacokinetics of TAK-041 in healthy participants and patients with stable schizophrenia . British Journal of Clinical Pharmacology . August 2022 . 88 . 8 . 3872–3882 . 10.1111/bcp.15305. 35277995 . 247407736 . free . 9544063 .
4. Rabiner . Eugenii A. . Uz . Tolga . Mansur . Ayla . Brown . Terry . Chen . Grace . Wu . Jingtao . Atienza . Joy . Schwarz . Adam J. . Yin . Wei . Lewis . Yvonne . Searle . Graham E. . Dennison . Jeremy M. T. J. . Passchier . Jan . Gunn . Roger N. . Tauscher . Johannes . Endogenous dopamine release in the human brain as a pharmacodynamic biomarker: evaluation of the new GPR139 agonist TAK-041 with [11C]PHNO PET . Neuropsychopharmacology . June 2022 . 47 . 7 . 1405–1412 . 10.1038/s41386-021-01204-1. 34675381 . 9117280 .
5. Reichard . Holly A. . Schiffer . Hans H. . Monenschein . Holger . Atienza . Josephine M. . Corbett . Gerard . Skaggs . Alton W. . Collia . Deanna R. . Ray . William J. . Serrats . Jordi . Bliesath . Joshua . Kaushal . Nidhi . Lam . Betty P. . Amador-Arjona . Alejandro . Rahbaek . Lisa . McConn . Donavon J. . Mulligan . Victoria J. . Brice . Nicola . Gaskin . Philip L. R. . Cilia . Jackie . Hitchcock . Stephen . Discovery of TAK-041: a Potent and Selective GPR139 Agonist Explored for the Treatment of Negative Symptoms Associated with Schizophrenia . Journal of Medicinal Chemistry . 12 August 2021 . 64 . 15 . 11527–11542 . 10.1021/acs.jmedchem.1c00820. 34260228 . 235908256 .
6. Münster . Alexandra . Sommer . Susanne . Kúkeľová . Diana . Sigrist . Hannes . Koros . Eliza . Deiana . Serena . Klinder . Klaus . Baader-Pagler . Tamara . Mayer-Wrangowski . Svenja . Ferger . Boris . Bretschneider . Tom . Pryce . Christopher R. . Hauber . Wolfgang . von Heimendahl . Moritz . Effects of GPR139 agonism on effort expenditure for food reward in rodent models: Evidence for pro-motivational actions . Neuropharmacology . August 2022 . 213 . 109078 . 10.1016/j.neuropharm.2022.109078. 35561791 . 248574904 . free .
7. News: Taylor . Nick Paul . Neurocrine hit with one-two punch as Takeda and Xenon pacts deliver midphase flops . 4 December 2023 . Fierce Biotech . 10 November 2023.