Carglumic Acid

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Cat Number

API0232153

CAS Number

1188-38-1

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Product Detail Description Scientific Support Customer Q&A

CAS Number

1188-38-1

EINECS

601-569-3

Storage

Store at room temperature

Synonyms

N-Carbamyl-L-glutamic acid; Carbaglu; (2S)-2-(carbamoylamino)pentanedioic acid; Ureidoglutaric acid; Carbamylglutamic acid

Molecular Formula

C6H10N2O5

Molecular Weight

190.15

Smiles

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

Appearance

White to off-white powder

Melting Point

174°C

Boiling Point

438.1±45.0°C at 760 mmHg (Predicted)

Relative Density

1.499±0.06 (Predicted)

General Description

Carglumic acid (N‑carbamyl‑L‑glutamic acid) is a synthetic analogue of N‑acetylglutamate (NAG), the essential allosteric activator of carbamoyl phosphate synthetase 1 (CPS1) in the urea cycle. Its structure replaces the acetyl group of NAG with a carbamyl group. The molecule is a small, water‑soluble dicarboxylic acid that is chemically stable and orally bioavailable.

Mechanism of Action

Carglumic acid activates CPS1 in the mitochondria of hepatocytes, mimicking the physiological activator NAG. CPS1 catalyzes the first and rate‑limiting step of the urea cycle, converting ammonia and bicarbonate into carbamoyl phosphate. In patients with NAG synthase (NAGS) deficiency, carglumic acid restores ureagenesis, reducing toxic ammonia levels.

Application

Carglumic acid is indicated for the treatment of acute and chronic hyperammonemia due to N‑acetylglutamate synthase (NAGS) deficiency, a rare urea cycle disorder. It is also used off‑label for propionic acidemia and methylmalonic acidemia when hyperammonemia is present.

Post‑hoc analysis of two retrospective studies (98 decompensation episodes in organic acidurias) compared carglumic acid, ammonia scavengers, or their combination for hyperammonemia. Baseline ammonia was highest in the combination group (271 µmol/L) and carglumic acid alone (199 µmol/L) versus scavengers alone (122 µmol/L). At 0‑12 hours, the combination reduced ammonia by 27% (vs. +12% with scavengers alone, p<0.05). At 48‑72 hours, reductions were 76% (combination), 66% (carglumic acid), and 16% (scavengers alone). Adverse events were similar across groups. Carglumic acid, alone or combined, is more effective than scavengers alone in the first 72 hours.

Fig. 1 Median plasma NH3 levels during the first 72 h of treatmen. (Chakrapani A, et al., 2018)

References

Chakrapani A, et al. Effect of carglumic acid with or without ammonia scavengers on hyperammonaemia in acute decompensation episodes of organic acidurias. Orphanet J Rare Dis. 2018;13(1):97.

Does Carglumic Acid require protection from moisture during storage?

Yes, it is hygroscopic and readily absorbs moisture, leading to clumping and potential hydrolysis. Store in tightly sealed, moisture-proof containers with desiccant.

What is the recommended storage temperature for Carglumic Acid?

Store at controlled room temperature (15-25°C). Avoid excessive heat above 30°C, which can accelerate decarboxylation and degradation to glutamic acid.

Is Carglumic Acid stable in oral suspension formulations for pediatric use?

Reconstituted suspensions must be used within a short period (typically 24-48 hours under refrigeration).

How is the impurity glutamic acid (hydrolysis product) monitored?

This degradation product is quantified using a stability-indicating HPLC method with pre-column derivatization, ensuring it remains within ICH limits.