In a dose-dependent way, carglumic acid decreases the cell viability of human non-small cell lung cancer, triple-negative breast cancer, pancreatic ductal adenocarcinoma, and liver cancer cell lines. For these cell lines, the range of carglumic acid's 50% inhibitory concentration (IC50) is 5 to 7.5 mM. The findings show that kagaric acid does not cause a total stoppage of the cell cycle. AsPC1 and MDA-MB-231 cells treated with karglulic acid, on the other hand, had a higher number of sub-G1 cells than untreated cells. In AsPC1 and HPDE-E6E7 cells, the IC50 of carbamic acid was 5 mM and more than 10 mM, respectively. The IC50 of carboxylic acid is 5 mM in MDA-MB-231 and 6 mM in MCF-12A cells, respectively[1].

The findings demonstrated that karglulic acid markedly slowed tumor growth, but not the vehicle control. On day 21, karglulic acid's tumor growth-inhibiting rate in the orthotopic pancreatic cancer model was 80% (P<0.01). On day 20, 82% (P<0.01) of the orthotopic triple-negative breast cancer model's tumor development was inhibited by karglulic acid. These findings suggest that karglulic acid suppresses triple-negative breast cancer and pancreatic cancer tumor growth. On day 20, animals receiving oral and intravenous treatment had average tumor growth inhibition rates of 55% and 93%, respectively (P<0.01) [1].

Absorption, Distribution and Excretion
30% bioavailability; Cmax, mean, 100 mg/kg dose = 2.6 μg/mL (range 1.9–4.8). Carbohydrate does not undergo intracellular degradation. Following a single oral dose of 100 mg/kg body weight of radiolabeled carbohydrate, 9% of the dose is excreted unchanged in the urine, and up to 60% is excreted unchanged in the feces. Apparent volume of distribution is 2657 L (range: 1616–5797). Apparent total clearance is 5.7 L/min (range 3.0–9.7), renal clearance is 290 mL/min (range 204–445), and 24-hour urinary excretion is 4.5% of the dose (range 3.5–7.5). Metabolism/Metabolites Some carbohydrate may be metabolized by gut microbiota. The final product of caloglutamate metabolism is likely carbon dioxide, which is excreted through the lungs.

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Biological Half-Life
The median terminal half-life is 5.6 hours (range 4.3–9.5).

[1]. Carglumic acid promotes apoptosis and suppresses cancer cell proliferation in vitro and in vivo. Am J Cancer Res. 2015 Nov 15;5(12):3560-9.

Carboglutamate is a urea, an N-carbamoyl derivative of L-glutamate. It is an orphan drug used to treat N-acetylglutamate synthase deficiency, which leads to acute hyperammonemia. Carboglutamate is both an orphan drug and an activator of carbamoyl phosphate synthase I. It is an N-acyl-L-glutamate, belonging to the urea class of compounds. It is the conjugate acid of N-carbamoyl-L-glutamate (2-). Carboglutamate is used to treat hyperammonemia in patients with N-acetylglutamate synthase deficiency. This rare, inherited disease causes elevated ammonia levels in the blood, which can eventually cross the blood-brain barrier, causing neurological problems, cerebral edema, coma, and even death. Carboglutamate was approved by the U.S. Food and Drug Administration (FDA) on March 18, 2010. Carboglutamate is a carbamoyl phosphate synthase 1 activator. The mechanism of action of carboglutamate is as a carbamoyl phosphate synthase 1 activator.
There are reports and data regarding the role of carboglutamate in C. elegans.
Carboglutamate is an orally effective synthetic structural analogue, an analogue of N-acetylglutamate (NAG) and carbamoyl phosphate synthase 1 (CPS 1), with ammonia-lowering activity. NAG is produced by the hepatic enzyme N-acetylglutamate synthase (NAGS) and is an important allosteric activator of carbamoyl phosphate synthase 1 (CPS 1). CPS 1 plays an important role in the urea cycle, converting ammonia to urea. Oral administration of carboglutamate can replace NAG in patients with NAGS deficiency and activate CPS 1, thereby preventing hyperammonemia.
Pharmaceutical Indications

For the treatment of acute and chronic hyperammonemia in patients with N-acetylglutamate synthase (NAGS) deficiency. This enzyme is an important component of the urea cycle and prevents the accumulation of neurotoxic ammonium in the blood.

FDA Label
Carbaglu is indicated for the treatment of: hyperammonemia caused by primary N-acetylglutamate synthase deficiency; hyperammonemia caused by isovaleric acidemia; hyperammonemia caused by methylmalonic acidemia; and hyperammonemia caused by propionic acidemia.
Ucedane is indicated for the treatment of: hyperammonemia caused by primary N-acetylglutamate synthase deficiency; hyperammonemia caused by isovaleric acidemia; hyperammonemia caused by methylmalonic acidemia; and hyperammonemia caused by propionic acidemia.

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Mechanism of Action
Carbaglu is a synthetic structural analog of N-acetylglutamate (NAG), an important allosteric activator of the liver enzyme carbamoyl phosphate synthase 1 (CPS1). CPS1, located in mitochondria, is the first enzyme in the urea cycle, responsible for converting ammonia into urea. Carbaglu treats NAG deficiency patients by activating CPS1, but it does not participate in the regulation of the urea cycle.

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Pharmacodynamics
The median time to peak concentration (Tmax) of carboglutamate is 3 hours (range: 2–4 hours). The daily dose range of carboglutamate is 100 to 250 mg/kg, usually adjusted to maintain normal plasma ammonia levels.

C6H10N2O5

190.154

190.059

1188-38-1

121396

White to off-white solid powder

1.499g/cm3

438.1ºC at 760 mmHg

174°

218.8ºC

6.7E-09mmHg at 25°C

1.544

0.063

4

5

5

13

227

1

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

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

(2S)-2-(carbamoylamino)pentanedioic acid

Carglumic Acid; OE312, OE-312, OE 312, AJ 266447, AJ-26647, AJ26647

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~525.90 mM)
H2O : ~10 mg/mL (~52.59 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (13.15 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (13.15 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (13.15 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 37.5 mg/mL (197.21 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)