CARGLUMIC ACID

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 Search

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

Molecular Formula	C6H10N2O5
Molecular Weight	190.154
Charge	0
Count

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

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022562lbl.pdf | http://www.recordati.com/resources/Pubblicazione/___e5f362471c2c448d873585839d6dd521_/carbaglu-authorized-in-canada.pdf

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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Carbamoyl-phosphate synthase [ammonia], mitochondrial 2 Target ID: CHEMBL2362990 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21403788	Positive Allosteric Modulator 186

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute hyperammonemia 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022562lbl.pdf	Primary		Approved 8583	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 2010
Chronic hyperammonemia 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022562lbl.pdf	Palliative		Approved 8583	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 2010

C_max

Value	Dose	Co-administered	Analyte	Population
2892 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25677217/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/30780843/	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

Value	Dose	Co-administered	Analyte	Population
23.2 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25677217/	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25677217/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/30780843/	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

Dose	Population	Adverse 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: https://ojrd.biomedcentral.com/articles/10.1186/s13023-016-0406-2	unhealthy, 5 day Health Status: unhealthy Age Group: 5 day Sex: M+F Sources: https://ojrd.biomedcentral.com/articles/10.1186/s13023-016-0406-2	Sources: https://ojrd.biomedcentral.com/articles/10.1186/s13023-016-0406-2

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2B6 926 CYP2A6 879 CYP2C8 1057 CYP2C19 2057 CYP2E1 1060 CYP3A4/5 296	CYP1A 26 CYP2B 10 CYP1A2 1197	CYP1A 59 CYP2B6 669 CYP3A4/5 133

Drug as perpetrator

Target	Modality	Activity
CYP1A 122	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_A100_2.pdf#page=23, https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_I100_1.pdf#page=38 Page: (PMDA_A100_2 in Japanese) 23, (PMDA_I100_1 in Japanese) 11-12, 38	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_A100_2.pdf#page=23, https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_I100_1.pdf#page=12 Page: (PMDA_A100_2 in Japanese) 23, (PMDA_I100_1 in Japanese) 12, 39-42	no
CYP2A6 911	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_A100_2.pdf#page=23, https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_I100_1.pdf#page=12 Page: (PMDA_A100_2 in Japanese) 23, (PMDA_I100_1 in Japanese) 12, 39-42	no
CYP2B6 1160	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_A100_2.pdf#page=23, https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_I100_1.pdf#page=38 Page: (PMDA_A100_2 in Japanese) 23, (PMDA_I100_1 in Japanese) 11-12, 38	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_A100_2.pdf#page=23, https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_I100_1.pdf#page=12 Page: (PMDA_A100_2 in Japanese) 23, (PMDA_I100_1 in Japanese) 12, 39-42	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_A100_2.pdf#page=23, https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_I100_1.pdf#page=12 Page: (PMDA_A100_2 in Japanese) 23, (PMDA_I100_1 in Japanese) 12, 39-42	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_A100_2.pdf#page=23, https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_I100_1.pdf#page=12 Page: (PMDA_A100_2 in Japanese) 23, (PMDA_I100_1 in Japanese) 12, 39-42	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_A100_2.pdf#page=23, https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_I100_1.pdf#page=12 Page: (PMDA_A100_2 in Japanese) 23, (PMDA_I100_1 in Japanese) 12, 39-42	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_A100_2.pdf#page=23, https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_I100_1.pdf#page=12 Page: (PMDA_A100_2 in Japanese) 23, (PMDA_I100_1 in Japanese) 12, 39-42	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_A100_2.pdf#page=23, https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_I100_1.pdf#page=12 Page: (PMDA_A100_2 in Japanese) 23, (PMDA_I100_1 in Japanese) 12, 39-42	no
CYP3A4/5 357	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_A100_2.pdf#page=23, https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_I100_1.pdf#page=38 Page: (PMDA_A100_2 in Japanese) 23, (PMDA_I100_1 in Japanese) 11-12, 38	no
CYP3A4/5 357	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_A100_2.pdf#page=23, https://www.pmda.go.jp/drugs/2016/P20161021006/710794000_22800AMX00708_I100_1.pdf#page=12 Page: (PMDA_A100_2 in Japanese) 23, (PMDA_I100_1 in Japanese) 12, 39-42	no

Drug as victim

Target	Modality	Activity
CYP1A 26	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022562s000pharmr.pdf#page=30 Page: 30, 35	no
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022562s000pharmr.pdf#page=30 Page: 30.0	no
CYP2B 10	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022562s000pharmr.pdf#page=30 Page: 30.0	no
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022562s000pharmr.pdf#page=30 Page: 30.0	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:71028	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:71028
ChemicalBook	CB6183743	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6183743
eMolecules	8294431	https://www.emolecules.com/cgi-bin/more?vid=8294431
MolPort	MolPort-012-207-739	https://www.molport.com/shop/molecule-link/MolPort-012-207-739
ZINC	ZINC000001530283	http://zinc15.docking.org/substances/ZINC000001530283

PubMed

Title	Date	PubMed
[Orphan drugs and metabolic disorders].	2001 Aug 1-15	11588713
Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients.	2001 Sep	11518822
N-acetylglutamate synthase deficiency and the treatment of hyperammonemic encephalopathy.	2002 Dec	12447942
N-carbamylglutamate enhances ammonia detoxification in a patient with decompensated methylmalonic aciduria.	2003 Aug	12948747
Hyperammonaemia as a cause of psychosis in an adolescent.	2003 Nov	12942317
Mammalian N-acetylglutamate synthase.	2004 Apr	15050968
Carglumic acid: new preparation. An advance in rare urea cycle disorders.	2004 Feb	15055204
Urea synthesis by ruminal epithelial and duodenal mucosal cells from growing sheep.	2004 Jun	15453495
Restoration of ureagenesis in N-acetylglutamate synthase deficiency by N-carbamylglutamate.	2004 Oct	15480384
N-carbamylglutamate protects patients with decompensated propionic aciduria from hyperammonaemia.	2005	15877213
Misleading diagnosis of partial N-acetylglutamate synthase deficiency based on enzyme measurement corrected by mutation analysis.	2005 Jan	15858972
Mutations and polymorphisms in the human N-acetylglutamate synthase (NAGS) gene.	2007 Aug	17421020
Carglumic acid: a second look. Confirmed progress in a rare urea cycle disorder.	2008 Apr	18516804
N-carbamylglutamate markedly enhances ureagenesis in N-acetylglutamate deficiency and propionic acidemia as measured by isotopic incorporation and blood biomarkers.	2008 Aug	18414145
Carglumic acid: an additional therapy in the treatment of organic acidurias with hyperammonemia?	2008 Jan 30	18234091
[A newborn infant with hyperventilation].	2008 Jun 26	18604903
N-acetylglutamate synthase: structure, function and defects.	2010	20303810
N-carbamylglutamate in emergency management of hyperammonemia in neonatal acute onset propionic and methylmalonic aciduria.	2010	19887858
Outpatient treatment of propionic acidemia-associated hyperammonemia with N-carbamoyl-L-glutamate in an infant.	2010 Apr	20435240
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	20213438
Gateways to clinical trials.	2010 Dec	21225012
Carglumic acid approved to treat genetic hyperammonemia.	2010 May 1	20410539

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:31:50 GMT 2025` Edited by `admin` on `Mon Mar 31 18:31:50 GMT 2025`
Record UNII	5L0HB4V1EW
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CARGLUMIC ACID

Official Name

English

CARBAGLU

Preferred 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

N-CARBAMOYL-L-GLUTAMIC ACID

Systematic Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

CARBAGLU (AUTHORIZED: AMINO ACID METABOLISM, INBORN ERRORS)