TALTIRELIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H23N7O5
Molecular Weight	405.4084
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C(=O)C[C@H](NC1=O)C(=O)N[C@@H](CC2=CN=CN2)C(=O)N3CCC[C@H]3C(N)=O

InChI

InChIKey=LQZAIAZUDWIVPM-SRVKXCTJSA-N

InChI=1S/C17H23N7O5/c1-23-13(25)6-10(22-17(23)29)15(27)21-11(5-9-7-19-8-20-9)16(28)24-4-2-3-12(24)14(18)26/h7-8,10-12H,2-6H2,1H3,(H2,18,26)(H,19,20)(H,21,27)(H,22,29)/t10-,11-,12-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C17H23N7O5
Molecular Weight	405.4084
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15931571
Curator's Comment: description was created based on several sources, including https://www.drugs.com/international/taltirelin.html | https://www.ncbi.nlm.nih.gov/pubmed/23087672 | https://www.ncbi.nlm.nih.gov/pubmed/25142535

Taltirelin (TA-0910), a synthetic thyrotropin-releasing hormone (TRH) analog, has been developed by Tanabe Seiyaku for the treatment of neurodegenerative diseases. Taltirelin mimics the physiological actions of TRH, but with a much longer half-life and duration of effects, and little development of tolerance following prolonged dosing. Taltirelin has nootropic, neuroprotective and analgesic effects. Taltirelin is primarily being researched for the treatment of spinocerebellar ataxia; limited research has also been carried out with regard to other neurodegenerative disorders, e.g., spinal muscular atrophy.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thyrotropin-releasing hormone receptor 10 Target ID: CHEMBL1810 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23087672	Agonist 2678		36.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Spinocerebellar degeneration 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15931571	Primary		Approved 8429	Ceredist Approved Use Unknown

PubMed

Title	Date	PubMed
Taltirelin (Tanabe Seiyaku).	2001 Dec	15931571
Brain receptor binding characteristics and pharmacokinetic-pharmacodynamic analysis of thyrotropin-releasing hormone analogues.	2001 Dec 28	11833715
Neuroprotective effect and brain receptor binding of taltirelin, a novel thyrotropin-releasing hormone (TRH) analogue, in transient forebrain ischemia of C57BL/6J mice.	2002 Dec 20	12467901
Determination of taltirelin, a new stable thyrotropin-releasing hormone analogue, in human plasma by high-performance liquid chromatography turbo-ionspray ionization tandem mass spectrometry.	2002 Nov 7	12408927
Blood-brain permeability of [3H]-(3-methyl-His2)thyrotropin-releasing hormone (MeTRH) in mice: effects of TRH and its analogues.	2003	15618750
Studies on the transport of thyrotropin-releasing hormone (TRH) analogues in Caco-2 cell monolayers.	2003 May	12831502
Lack of behavioral tolerance by repeated treatment with taltirelin hydrate, a thyrotropin-releasing hormone analog, in rats.	2005 Dec	16368129
Taltirelin improves motor ataxia independently of monoamine levels in rolling mouse nagoya, a model of spinocerebellar atrophy.	2005 Dec	16327158
The synthetic TRH analogue taltirelin exerts modality-specific antinociceptive effects via distinct descending monoaminergic systems.	2007 Feb	17220907
Excitation of locus coeruleus noradrenergic neurons by thyrotropin-releasing hormone.	2009 Dec 1	19840999
The ataxic Cacna1a-mutant mouse rolling nagoya: an overview of neuromorphological and electrophysiological findings.	2009 Sep	19484318
Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor.	2012	23087672
Thyrotropin-releasing hormone receptor type 1 (TRH-R1), not TRH-R2, primarily mediates taltirelin actions in the CNS of mice.	2013 May	23303050

Patents

Sample Use Guides

In Vivo Use Guide

Patients took taltirelin (5 mg bid) or placebo for 28 to 52 weeks.

Route of Administration: Oral

In Vitro Use Guide

HEK-EM 293 (human embryonic kidney) cells stably expressing TRH-R were seeded in black-walled, clear bottomed 96-well plates (Corning, NY, USA) at a density of 60,000 cells/well in DMEM with 10% fetal bovine serum and incubatedfor24hat37◦C in5%CO2. The following day, the culture media was replaced with 100 μl of Hank’s balanced salt solution with 20 mM HEPES, pH 7.5 and the cells were loaded with100 μl of calcium 4 fluorescent dye (Molecular Devices, Sunnyvale, CA, USA) for 1 h at room temperature before addition of compounds .Transient changes in intracellular [Ca++] induced by TALTIRELIN were measured using the FLIPRTETRA system (Molecular Devices, Sunnyvale, CA, USA). Changes in fluorescence were detected at the emission wavelength ranges from 515 to 575 nm. The agonistic responses of ligands were assessed immediately upon their addition in a concentration range from 0.1 nMto30 μM.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:20:16 UTC 2023` Edited by `admin` on `Sat Dec 16 16:20:16 UTC 2023`
Record UNII	DOZ62MV6A5
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TALTIRELIN

Official Name

English

TALTIRELIN [MART.]

Common Name

English

TALTIRELIN [MI]

Common Name

English

TA-0910

Code

English

taltirelin [INN]

Common Name

English

Taltirelin [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C76367