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Details

Stereochemistry ABSOLUTE
Molecular Formula C6H10N2O5
Molecular Weight 190.1543
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CARGLUMIC ACID

SMILES

C(CC(=O)O)[C@@]([H])(C(=O)O)NC(=N)O

InChI

InChIKey=LCQLHJZYVOQKHU-VKHMYHEASA-N
InChI=1S/C6H10N2O5/c7-6(13)8-3(5(11)12)1-2-4(9)10/h3H,1-2H2,(H,9,10)(H,11,12)(H3,7,8,13)/t3-/m0/s1

HIDE SMILES / InChI
Carglumic acid is a Carbamoyl Phosphate Synthetase 1 (CPS 1) allosteric modulator. CPS1 is found in the mitochondria and is the first enzyme of the urea cycle, which converts ammonia into urea. Carglumic acid acts as a replacement for NAG in NAGS deficiency patients by activating CPS1 but it does not help to regulate the urea cycle. Carglumic acid under the trade name Carbaglu indicated as adjunctive therapy for the treatment of acute hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthase (NAGS). In addition, as maintenance therapy for the treatment of chronic hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthase (NAGS). This rare genetic disorder results in elevated blood levels of ammonia, which can eventually cross the blood–brain barrier and cause neurologic problems, cerebral edema, coma, and death.

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CARBAGLU

Approved Use

Carbaglu (carglumic acid) is a Carbamoyl Phosphate Synthetase 1 (CPS 1) activator indicated as: • Adjunctive therapy for the treatment of acute hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthase (NAGS). (1.1) • Maintenance therapy for the treatment of chronic hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthase (NAGS). (1.2)

Launch Date

1.26887041E12
Palliative
CARBAGLU

Approved Use

Carbaglu (carglumic acid) is a Carbamoyl Phosphate Synthetase 1 (CPS 1) activator indicated as: • Adjunctive therapy for the treatment of acute hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthase (NAGS). (1.1) • Maintenance therapy for the treatment of chronic hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthase (NAGS). (1.2)

Launch Date

1.26887041E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2892 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARGLUMIC ACID plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
2.6 μg/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARGLUMIC ACID plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
23.2 μg × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARGLUMIC ACID plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5.2 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARGLUMIC ACID plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
5.6 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARGLUMIC ACID plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
96.3 mg/kg 2 times / day multiple, oral
Recommended
Dose: 96.3 mg/kg, 2 times / day
Route: oral
Route: multiple
Dose: 96.3 mg/kg, 2 times / day
Sources:
unhealthy, 5 day
n = 21
Health Status: unhealthy
Condition: methylmalonic aciduria
Age Group: 5 day
Sex: M+F
Population Size: 21
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
Drug as victim
PubMed

PubMed

TitleDatePubMed
[Orphan drugs and metabolic disorders].
2001 Aug 1-15
Mixture of N-carbamoyl-L-glutamate plus L-arginine can protect rats with liver cirrhosis from acute ammonia intoxication.
2001 Dec
Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients.
2001 Sep
N-acetylglutamate synthase deficiency and the treatment of hyperammonemic encephalopathy.
2002 Dec
N-carbamylglutamate enhances ammonia detoxification in a patient with decompensated methylmalonic aciduria.
2003 Aug
Hyperammonaemia as a cause of psychosis in an adolescent.
2003 Nov
Mammalian N-acetylglutamate synthase.
2004 Apr
Carglumic acid: new preparation. An advance in rare urea cycle disorders.
2004 Feb
Urea synthesis by ruminal epithelial and duodenal mucosal cells from growing sheep.
2004 Jun
Restoration of ureagenesis in N-acetylglutamate synthase deficiency by N-carbamylglutamate.
2004 Oct
N-carbamylglutamate protects patients with decompensated propionic aciduria from hyperammonaemia.
2005
Neonatal hyperammonemia: the N-carbamoyl-L-glutamic acid test.
2005 Aug
Misleading diagnosis of partial N-acetylglutamate synthase deficiency based on enzyme measurement corrected by mutation analysis.
2005 Jan
Metabolic fates of ammonia-N in ruminal epithelial and duodenal mucosal cells isolated from growing sheep.
2005 Nov
Mutations and polymorphisms in the human N-acetylglutamate synthase (NAGS) gene.
2007 Aug
A trial with N-carbamylglutamate may not detect all patients with NAGS deficiency and neonatal onset.
2007 Jun
Carglumic acid: a second look. Confirmed progress in a rare urea cycle disorder.
2008 Apr
N-carbamylglutamate markedly enhances ureagenesis in N-acetylglutamate deficiency and propionic acidemia as measured by isotopic incorporation and blood biomarkers.
2008 Aug
N-carbamylglutamate for neonatal hyperammonaemia in propionic acidaemia.
2008 Dec
Carglumic acid: an additional therapy in the treatment of organic acidurias with hyperammonemia?
2008 Jan 30
[A newborn infant with hyperventilation].
2008 Jun 26
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes.
2009
[N-carbamyl glutamate treatment in hyperammoniemia decompensated propionic acidaemia].
2009 Dec
Effects of a single dose of N-carbamylglutamate on the rate of ureagenesis.
2009 Dec
Pricing of orphan drugs.
2009 Feb 7
The first use of N-carbamylglutamate in a patient with decompensated maple syrup urine disease.
2009 Sep
N-acetylglutamate synthase: structure, function and defects.
2010
N-carbamylglutamate in emergency management of hyperammonemia in neonatal acute onset propionic and methylmalonic aciduria.
2010
Outpatient treatment of propionic acidemia-associated hyperammonemia with N-carbamoyl-L-glutamate in an infant.
2010 Apr
Dietary supplementation with L-arginine or N-carbamylglutamate enhances intestinal growth and heat shock protein-70 expression in weanling pigs fed a corn- and soybean meal-based diet.
2010 Aug
Gateways to clinical trials.
2010 Dec
Favourable long-term outcome after immediate treatment of neonatal hyperammonemia due to N-acetylglutamate synthase deficiency.
2010 Feb
Biochemical efficacy of N-carbamylglutamate in neonatal severe hyperammonaemia due to propionic acidaemia.
2010 Jan
N-carbamylglutamate augments ureagenesis and reduces ammonia and glutamine in propionic acidemia.
2010 Jul
Carglumic acid approved to treat genetic hyperammonemia.
2010 May 1
Role of carglumic acid in the treatment of acute hyperammonemia due to N-acetylglutamate synthase deficiency.
2011
Patents

Sample Use Guides

Adult Dosage: The recommended initial dose for acute hyperammonemia is 100 mg/kg/day to 250 mg/kg/day. Concomitant administration of other ammonia lowering therapies is recommended. Dosing should be titrated based on individual patient plasma ammonia levels and clinical symptoms. The recommended maintenance dose should be titrated to target normal plasma ammonia level for age. Based on limited data in 22 patients receiving maintenance treatment with Carbaglu in a retrospective case series, maintenance doses were usually less than 100 mg/kg/day. The total daily dose should be divided into 2 to 4 doses and rounded to the nearest 100 mg. (i.e. half a Carbaglu Tablet) Pediatric Dosage: The recommended initial dose for acute hyperammonemia is 100 mg/kg/day to 250 mg/kg/day. Concomitant administration of other ammonia lowering therapies is recommended. Dosing should be titrated based on individual patient plasma ammonia levels and clinical symptoms. The recommended maintenance dose should be titrated to target normal plasma ammonia level for age. Based on limited data in 22 patients receiving maintenance treatment with Carbaglu in a retrospective case series, maintenance doses were usually less than 100 mg/kg/day. The total daily dose should be divided into 2 to 4 doses.
Route of Administration: Oral
Carglumic acid-treated (1, 5, 10 mM) and untreated cancer cells were stained with propidium iodide to determine DNA contents in the human pancreatic adenocarcinoma cell lines, AsPC1 and human triple-negative breast cancer cell lines MDA-MB-231. The results showed that carglumic acid did not induce complete cell cycle arrest. Instead, we observed more sub-G1 cells among carglumic acid-treated AsPC1 and MDA-MB-231 cells than among untreated cells, indicating that cell death occurred in response to carglumic acid. Sub-G1 cells accounted for 1.6% and 26.3% of untreated and treated AsPC1 cells, respectively , and for 1.8% and 12.8% of untreated and treated MDA-MB-231 cells, respectively. In order to further determine whether cancer cells under go cell death through apoptosis after carglumic acid treatment, we measured caspase activity in AsPC1 cells treated with carglumic acid. The results showed that caspase-3 activity increased in a dose-dependent manner. Together, these data suggest that carglumic acid inhibits cancer cell proliferation by inducing apoptosis.
Name Type Language
CARGLUMIC ACID
DASH   EMA EPAR   INN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
CARBAMYL-L-GLUTAMIC ACID
Systematic Name English
N-CARBAMYL-L-GLUTAMIC ACID
Common Name English
L-GLUTAMIC ACID, N-(AMINOCARBONYL)-
Common Name English
CARGLUMIC ACID [JAN]
Common Name English
CARGLUMIC ACID [EMA EPAR]
Common Name English
CARGLUMIC ACID [USP-RS]
Common Name English
CARGLUMIC ACID [ORANGE BOOK]
Common Name English
CARGLUMIC ACID [MART.]
Common Name English
OE-312
Code English
NSC-760124
Code English
OE 312
Code English
CARGLUMIC ACID [MI]
Common Name English
CARGLUMIC ACID [INN]
Common Name English
N-CARBAMYLGLUTAMATE
Systematic Name English
CARGLUMIC ACID [WHO-DD]
Common Name English
CARGLUMIC ACID [VANDF]
Common Name English
CARGLUMIC ACID [USAN]
Common Name English
CARBAGLU
Brand Name English
N-CARBAMOYL-L-GLUTAMIC ACID
Systematic Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS CARBAGLU (AUTHORIZED: AMINO ACID METABOLISM, INBORN ERRORS)
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
FDA ORPHAN DRUG 109997
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
WHO-VATC QA16AA05
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
EU-Orphan Drug EU/3/00/007
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
NDF-RT N0000184144
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
WHO-ATC A16AA05
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
NCI_THESAURUS C78275
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
FDA ORPHAN DRUG 352111
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
Code System Code Type Description
EPA CompTox
1188-38-1
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
PRIMARY
MERCK INDEX
M3108
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
PRIMARY Merck Index
CAS
1188-38-1
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
PRIMARY
EVMPD
SUB20051
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
PRIMARY
WIKIPEDIA
CARGLUMIC ACID
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
PRIMARY
IUPHAR
7458
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
PRIMARY
DRUG CENTRAL
3068
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
PRIMARY
FDA UNII
5L0HB4V1EW
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
PRIMARY
NCI_THESAURUS
C76884
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
PRIMARY
INN
8008
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
PRIMARY
USP_CATALOG
1096586
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
PRIMARY USP-RS
RXCUI
401713
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
PRIMARY RxNorm
PUBCHEM
121396
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
PRIMARY
ChEMBL
CHEMBL1201780
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
PRIMARY
NDF-RT
N0000184143
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
PRIMARY Carbamoyl Phosphate Synthetase 1 Activators [MoA]
DRUG BANK
DB06775
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
PRIMARY
EVMPD
SUB13236MIG
Created by admin on Fri Jun 25 21:53:37 UTC 2021 , Edited by admin on Fri Jun 25 21:53:37 UTC 2021
ALTERNATIVE