U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C17H24N6O4S.4H2O
Molecular Weight 480.536
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MONTIRELIN TETRAHYDRATE

SMILES

O.O.O.O.C[C@H]1SC[C@H](NC1=O)C(=O)N[C@@H](CC2=CN=CN2)C(=O)N3CCC[C@H]3C(N)=O

InChI

InChIKey=LYTHVCBIYIODIA-UVZXXTSMSA-N
InChI=1S/C17H24N6O4S.4H2O/c1-9-15(25)22-12(7-28-9)16(26)21-11(5-10-6-19-8-20-10)17(27)23-4-2-3-13(23)14(18)24;;;;/h6,8-9,11-13H,2-5,7H2,1H3,(H2,18,24)(H,19,20)(H,21,26)(H,22,25);4*1H2/t9-,11+,12+,13+;;;;/m1..../s1

HIDE SMILES / InChI
Molecular Formula C17H24N6O4S
Molecular Weight 408.475
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
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

NS-3 (montirelin, CG 3703) is an analog of thyrotrophin releasing hormone (TRH). More potent and longer acting than TRH, CG-3703 produced beneficial effects in animal models of concussion-induced unconsciousness, cerebral ischemia, memory disruption, spontaneous convulsions in rats, narcolepsy, and spinal trauma. Given its efficacy in these models, the potential indications were broadened to include seizures, nerve trauma, cognitive dysfunction, and sleep apnea.

CNS Activity

CNS Active
4002
Curator's Comment: NS-3 (montirelin hydrate, CG 3703) can readily penetrate into the rodent brain. Centrally active TRH analogue CG3703 can improve neurological outcome and survival after brain injury in rats, perhaps through direct effects on cerebral metabolism. No available data on human.

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Thyrotropin-releasing hormone receptor
10
Target ID: Q01717
Gene ID: 25570.0
Gene Symbol: Trhr
Target Organism: Rattus norvegicus (Rat)
Agonist
2752
 35.2 nM [Ki]
Releasing Agent
8
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Primary
Basic research
Unknown

Approved Use

Unknown
Primary
Phase III
665
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Chronic oral administration of CG-3703, a thyrotropin releasing hormone analog, increases wake and decreases cataplexy in canine narcolepsy.
2000-07
Effects of thyrotropin-releasing hormone and its analogs on daytime sleepiness and cataplexy in canine narcolepsy.
1997-08-15
Effects of thyrotropin-releasing hormone and its analogue, NS-3, on blood pressure, heart rate, and serum catecholamine levels in rats.
1997-02
NS-3, a TRH-analog, reverses memory disruption by stimulating cholinergic and noradrenergic systems.
1996-02
NS-3(CG3703), a TRH analog, ameliorates scopolamine-induced memory disruption in rats.
1995-08
NS-3 (CG3703), an analog of thyrotropin-releasing hormone, ameliorates cognitive impairment in rats.
1995-04
Effect of NS-3, a thyrotropin-releasing hormone analog, on in vivo acetylcholine release in rat brain: regional differences and its sites of action.
1994-11
Differential affinities of TRH analogs at the mammalian spinal cord TRH receptor: implications for therapy in spinal injuries.
1989-09-25
Patents

Patents

DE10025947A1
2
EP0866711B1
2

Sample Use Guides

In Vivo Use Guide
Sources: Grünenthal (1997) Montirelin—A CNS Active TRH Analogue (Grünenthal GmbH, Aachen, Germany), pp 1–34. refernce retrieved from: http://jpet.aspetjournals.org/content/305/2/410.full
Curator's Comment: There are some evidences of Motirelin effectitivity on animal models: 1) two-week oral administration of CG-3703 (16 mg/kg) significantly reduced cataplexy and daytime sleep in canine narcolepsy http://www.ncbi.nlm.nih.gov/pubmed/10869884,9236248 2) Chronic intake of CNK-602A (NS-3, montirelin, CG 3703) in a dose that does not affect plasma levels of T3 and T4 inhibits tonic convulsions in Spontaneously epileptic rats and suggest that this drug may be an effective treatment for convulsive seizures in patients with epilepsy. http://www.ncbi.nlm.nih.gov/pubmed/8603636
0.5 mg of montirelin administered over 14 days improved ratings of global clinical state in 73% of patients exhibiting “disturbances of consciousness”.
Route of Administration: Unknown
In Vitro Use Guide
Curator's Comment: Among other TRH analogs montirelin (CG-3703) at concentrations 0.1-50 μM attenuated cell damage in retinoic acid differentiated SH-SY5Y cells
NS-3 (montirelin, CG 3703) is cytoprotective at 0.1-50 μM
Substance Class Chemical
Created
by admin
on Mon Mar 31 21:22:41 GMT 2025
Edited
by admin
on Mon Mar 31 21:22:41 GMT 2025
Record UNII
27MN0584ML
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MONTIRELIN HYDRATE
JAN  
Preferred Name English
MONTIRELIN TETRAHYDRATE
Common Name English
MONTIRELIN HYDRATE [JAN]
Common Name English
L-PROLINAMIDE, N-((6-METHYL-5-OXO-3-THIOMORPHOLINYL)CARBONYL)-L-HISTIDYL-, (3R-CIS)-, TETRAHYDRATE
Common Name English
Code System Code Type Description
PUBCHEM
53297483
Created by admin on Mon Mar 31 21:22:41 GMT 2025 , Edited by admin on Mon Mar 31 21:22:41 GMT 2025
PRIMARY
FDA UNII
27MN0584ML
Created by admin on Mon Mar 31 21:22:41 GMT 2025 , Edited by admin on Mon Mar 31 21:22:41 GMT 2025
PRIMARY
Related Record Type Details
Structure of MONTIRELIN
PARENT -> SALT/SOLVATE
Structure of MONTIRELIN
ANHYDROUS->SOLVATE
Related Record Type Details
Structure of MONTIRELIN
ACTIVE MOIETY
NIH
NCATS
PRIVACY NOTICE
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966