TILARGININE ACETATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C7H16N4O2.C2H4O2
Molecular Weight	248.2795
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(O)=O.CNC(=N)NCCC[C@H](N)C(O)=O

InChI

InChIKey=IKPNWIGTWUZCKM-JEDNCBNOSA-N

InChI=1S/C7H16N4O2.C2H4O2/c1-10-7(9)11-4-2-3-5(8)6(12)13;1-2(3)4/h5H,2-4,8H2,1H3,(H,12,13)(H3,9,10,11);1H3,(H,3,4)/t5-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C2H4O2
Molecular Weight	60.052
Charge	0
Count

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

Molecular Formula	C7H16N4O2
Molecular Weight	188.2275
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18808317
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12620067 | https://www.ncbi.nlm.nih.gov/pubmed/12182860 | https://clinicaltrials.gov/ct2/show/NCT00112281

Tilarginine is L-N-monomethyl arginine (L -NMMA), a non-selective inhibitor of nitric oxide synthase (NOS), which has been studied in the treatment of septic shock and cardiogenic shock complicating myocardial infarction. Despite strong evidence that excessive nitric oxide (NO) production plays a pivotal role in the pathogenesis of septic shock and may contribute to the pathogenesis of cardiogenic shock complicating myocardial infarction, outcome studies in these two disorders have proved disappointing. Tilarginine therapy was associated with an excess mortality, particularly at doses > 5 mg/(kg h), in septic shock, whereas the effects of a lower dose (1 mg/(kg h)) in cardiogenic shock complicating myocardial infarction were neutral. The excess mortality in patients with septic shock was almost certainly the result of unfavorable hemodynamic changes induced by Tilarginine (decreased cardiac output, increased pulmonary vascular resistance and reduced tissue oxygen delivery) whereas the lack of benefit in patients with cardiogenic shock complicating myocardial infarction may have been because the dose of Tilarginine was too low.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Nitric-oxide synthase, brain 24 Target ID: CHEMBL3568 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12620067	Inhibitor 8504	90.0 nM [IC50]
Nitric oxide synthase, inducible 55 Target ID: CHEMBL4481 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12182860	Inhibitor 8504	1000.0 nM [IC50]
Nitric-oxide synthase, endothelial 19 Target ID: CHEMBL4803 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12182860	Inhibitor 8504	540.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Shock, cardiogenic 4 Sources: https://clinicaltrials.gov/ct2/show/NCT00112281	Primary	Phase III 665	Unknown Approved Use Unknown
Obstructive sleep apnea 6 Sources: https://clinicaltrials.gov/ct2/show/NCT00410085	Primary	Phase IV 63	Unknown Approved Use Unknown
Obesity 206 Sources: https://clinicaltrials.gov/ct2/show/NCT01701973	Primary	Phase IV 63	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
12.9 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10336578/	3 mg/kg single, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.03 μg/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/9951425/	1 mg/kg/h single, intravenous dose: 1 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5.53 μg/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/9951425/	2.5 mg/kg/h single, intravenous dose: 2.5 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
22.9 μg/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/9951425/	5 mg/kg/h single, intravenous dose: 5 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
51.9 μg/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/9951425/	10 mg/kg/h single, intravenous dose: 10 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
128 μg/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/9951425/	20 mg/kg/h single, intravenous dose: 20 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
260.4 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10336578/	3 mg/kg single, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
16.6 μg × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/9951425/	1 mg/kg/h single, intravenous dose: 1 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
40.8 μg × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/9951425/	2.5 mg/kg/h single, intravenous dose: 2.5 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
175 μg × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/9951425/	5 mg/kg/h single, intravenous dose: 5 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
443 μg × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/9951425/	10 mg/kg/h single, intravenous dose: 10 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1640 μg × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/9951425/	20 mg/kg/h single, intravenous dose: 20 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
63.5 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10336578/	3 mg/kg single, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.3 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/9951425/	1 mg/kg/h single, intravenous dose: 1 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2.1 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/9951425/	2.5 mg/kg/h single, intravenous dose: 2.5 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3.1 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/9951425/	5 mg/kg/h single, intravenous dose: 5 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2.4 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/9951425/	10 mg/kg/h single, intravenous dose: 10 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
7.6 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/9951425/	20 mg/kg/h single, intravenous dose: 20 mg/kg/h route of administration: Intravenous experiment type: SINGLE co-administered:	TILARGININE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2C19 2057

Drug as perpetrator

Target	Modality	Activity
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/132862#section=BioAssay-Results Page: 12.0	inconclusive [IC50 15.8489 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/132862#section=BioAssay-Results Page: 31.0	inconclusive
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/132862#section=BioAssay-Results Page: 42.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/132862#section=BioAssay-Results Page: 48.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/132862#section=BioAssay-Results Page: 42.0	no

PubMed

Title	Date	PubMed
Expert opinion on tilarginine in the treatment of shock.	2008-10	18808317

Patents

Sample Use Guides

In Vivo Use Guide

Tilarginine was given as an intravenous infusion starting with a dose of 2.5 mg/(kg h), which could be subsequently increased in an incremental manner up to a maximum dose of 20 mg/(kg h).

Route of Administration: Intravenous

In Vitro Use Guide

L-NMMA (Tilarginine) was assayed for ability to inhibit NO production in human colorectal adenocarcinoma (DLD-1) cells preincubated with a cytokine cocktail. Cells were grown to confluence in 12-well plates. Cytokines or other agents were added to fresh media (1 mL/well). At 18-24-h postinduction, culture supernatants were harvested and stored at -20 C for nitrite analysis. Nitrite was measured spectrophotometrically using the Griess reagent

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:45:10 GMT 2025` Edited by `admin` on `Mon Mar 31 18:45:10 GMT 2025`
Record UNII	2FL3530AF2
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TILARGININE ACETATE

Official Name

English

NG-METHYLARGININE ACETATE

Preferred Name

English

ANO-1020

Code

English

L-NMMA ACETATE

Common Name

English

TARGININE ACETATE

Common Name

English

NG-MONOMETHYL-L-ARGININE ACETATE

Common Name

English

TILARGININE ACETATE [USAN]

Common Name

English

(2S)-2-Amino-5-[(methylcarbamimidoyl)amino]pentanoic acid monoacetate

Systematic Name

English

NG-METHYLARGININE ACETATE [MI]

Common Name

English

L-ORNITHINE, N(SUP 5)-(IMINO(METHYLAMINO)METHYL)-, MONOACETATE

Common Name

English

NG-METHYL-L-ARGININE ACETATE SALT

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29574