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

Details

Stereochemistry ABSOLUTE
Molecular Formula C6H10N2O5
Molecular Weight 190.154
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CARGLUMIC ACID

SMILES

NC(=O)N[C@@H](CCC(O)=O)C(O)=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
N-carbamylglutamate protects patients with decompensated propionic aciduria from hyperammonaemia.
2005
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
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes.
2009
Gateways to clinical trials.
2010 Dec
Favourable long-term outcome after immediate treatment of neonatal hyperammonemia due to N-acetylglutamate synthase deficiency.
2010 Feb
N-carbamylglutamate augments ureagenesis and reduces ammonia and glutamine in propionic acidemia.
2010 Jul
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
Carglumic acid [WHO-DD]
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 [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 Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
FDA ORPHAN DRUG 109997
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
WHO-VATC QA16AA05
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
EU-Orphan Drug EU/3/00/007
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
NDF-RT N0000184144
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
WHO-ATC A16AA05
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
NCI_THESAURUS C78275
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
FDA ORPHAN DRUG 352111
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
Code System Code Type Description
EPA CompTox
DTXSID7046706
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
MERCK INDEX
M3108
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY Merck Index
SMS_ID
100000089544
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
RS_ITEM_NUM
1096586
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
CAS
1188-38-1
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
EVMPD
SUB20051
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
WIKIPEDIA
CARGLUMIC ACID
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
DAILYMED
5L0HB4V1EW
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
IUPHAR
7458
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
NSC
760124
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
DRUG CENTRAL
3068
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
FDA UNII
5L0HB4V1EW
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
NCI_THESAURUS
C76884
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
USAN
XX-21
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
INN
8008
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
RXCUI
401713
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY RxNorm
PUBCHEM
121396
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
ChEMBL
CHEMBL1201780
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
NDF-RT
N0000184143
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY Carbamoyl Phosphate Synthetase 1 Activators [MoA]
CHEBI
71028
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
DRUG BANK
DB06775
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
PRIMARY
EVMPD
SUB13236MIG
Created by admin on Thu Jul 06 00:00:14 UTC 2023 , Edited by admin on Thu Jul 06 00:00:14 UTC 2023
ALTERNATIVE