TALTIRELIN TETRAHYDRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H23N7O5.4H2O
Molecular Weight	477.4695
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.O.O.O.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=HRCJDWMUKPHPHR-NTFWNTCYSA-N

InChI=1S/C17H23N7O5.4H2O/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);4*1H2/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

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 2752		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 8583	Ceredist Approved Use Unknown

T_1/2

Value	Dose	Co-administered	Analyte	Population
2 h REVIEW https://doi.org/10.1111/j.1527-3458.1998.tb00039.x	0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered:		TALTIRELIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
5 mg 1 times / day multiple, oral Studied dose Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: https://www.pmda.go.jp/drugs/2000/g000710/32ctdp_219-402.pdf#page=102	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.pmda.go.jp/drugs/2000/g000710/32ctdp_219-402.pdf#page=102	Sources: https://www.pmda.go.jp/drugs/2000/g000710/32ctdp_219-402.pdf#page=102

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087			inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP19A1 429	P-gp 2052

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/114750#section=Biological-Test-Results Page: 36.0	no
CYP3A4 2633	inducer 1966 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/114750#section=Biological-Test-Results Page: 38.0	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/114750#section=Biological-Test-Results Page: 38 \| 39	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/114750#section=Biological-Test-Results Page: 19.0

PubMed

Title	Date	PubMed
Thyrotropin-releasing hormone receptor type 1 (TRH-R1), not TRH-R2, primarily mediates taltirelin actions in the CNS of mice.	2013-05	23303050
Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor.	2012	23087672
Excitation of locus coeruleus noradrenergic neurons by thyrotropin-releasing hormone.	2009-12-01	19840999
The ataxic Cacna1a-mutant mouse rolling nagoya: an overview of neuromorphological and electrophysiological findings.	2009-09	19484318
The synthetic TRH analogue taltirelin exerts modality-specific antinociceptive effects via distinct descending monoaminergic systems.	2007-02	17220907
Lack of behavioral tolerance by repeated treatment with taltirelin hydrate, a thyrotropin-releasing hormone analog, in rats.	2005-12	16368129
Taltirelin improves motor ataxia independently of monoamine levels in rolling mouse nagoya, a model of spinocerebellar atrophy.	2005-12	16327158
Studies on the transport of thyrotropin-releasing hormone (TRH) analogues in Caco-2 cell monolayers.	2003-05	12831502
Blood-brain permeability of [3H]-(3-methyl-His2)thyrotropin-releasing hormone (MeTRH) in mice: effects of TRH and its analogues.	2003	15618750
Neuroprotective effect and brain receptor binding of taltirelin, a novel thyrotropin-releasing hormone (TRH) analogue, in transient forebrain ischemia of C57BL/6J mice.	2002-12-20	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.	2002-11-07	12408927
Brain receptor binding characteristics and pharmacokinetic-pharmacodynamic analysis of thyrotropin-releasing hormone analogues.	2001-12-28	11833715
Taltirelin (Tanabe Seiyaku).	2001-12	15931571

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 `Mon Mar 31 21:39:50 GMT 2025` Edited by `admin` on `Mon Mar 31 21:39:50 GMT 2025`
Record UNII	525OEO6W15
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TALTIRELIN HYDRATE

Preferred Name

English

TALTIRELIN TETRAHYDRATE

Common Name

English

TALTIRELIN TETRAHYDRATE [MI]

Common Name

English

Taltirelin tetrahydrate [WHO-DD]

Common Name

English

TALTIRELIN HYDRATE [JAN]

Common Name

English

L-PROLINAMIDE, N-(((4S)-HEXAHYDRO-1-METHYL-2,6-DIOXO-4-PYRIMIDINYL)CARBONYL)-L-HISTIDYL-, HYDRATE (1:4)

Systematic Name

English

CEREDIST

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C76367