Increasing dosages of ascorbic acid, but not the enzyme's cofactor 2-oxoglutarate, decreased the inhibitory impact of tiopronin (NMPG) on HPH-2 in an in vitro Von Hippel-Lindau protein binding experiment [2].

Myeloperoxidase activity is successfully decreased and colon damage is attenuated by tiopronin (NMPG). Moreover, in the inflammatory colon, NMPG dramatically reduced the expression of proinflammatory mediators. In human colon cancer cells, NMPG stimulates the production of hypoxia-inducible factor-1α (HIF-1α), which increases the secretion of vascular endothelial growth factor (VEGF). VEGF is a target of HIF-1 and is implicated in the healing of gastrointestinal mucosal ulcers. genetic material. By blocking HIF prolyl hydroxylase-2 (HPH-2), an enzyme that is crucial in adversely controlling the stability of the HIF-1α protein, NMPG causes the appearance of HIF-1α [2].

Absorption, Distribution and Excretion
Tiopronin undergoes slow absorption, reaching peak plasma concentration 3-6 hours after ingestion. In a study of healthy subjects, the bioavailability of total and unbound tiopronin was found to be 63% and 40%, respectively.
Tiopronin is 100% excreted in urine.
The volume of distribution of tiopronin is high at 455 L, indicating that a large portion of the drug is bound to tissues outside plasma.
Total renal clearance for the total and unbound fractions of tiopronin were found to be 3.3 and 13.3 L/h respectively.

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Metabolism / Metabolites
The principle metabolite of tiopronin is 2-mercaptopropionic acid (2-MPA). Between 10-15% of the drug is metabolized to 2-MPA via hydrolysis.

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Biological Half-Life
Tiopronin has a long terminal half life of 53 hours in healthy subjects. However, the unbound drug fraction of tiopronin is eliminated much more rapidly from plasma with a calculated half life of 1.8 hours.

Protein Binding
Tiopronin undergoes extensive protein binding in plasma. It is thought that this occurs through the formation of a disulphide bridge to the free thiol group of albumin.

[1]. Detection of tiopronin in body fluids and pharmaceutical products using red-emissive DNA-stabilized silver nanoclusters as a fluorescent probe. Mikrochim Acta. 2019 Aug 8;186(9):609.

[2]. N-(2-Mercaptopropionyl)-glycine, a diffusible antioxidant, activates HIF-1 by inhibiting HIF prolyl hydroxylase-2: implication in amelioration of rat colitis by the antioxidant. Biochem Biophys Res Commun. 2014 Jan 17;443(3):1008-13.

Tiopronin is a N-acyl-amino acid.
Tiopronin is a prescription thiol drug used primarily in the treatment of severe homozygous cystinuria. Patients with cystinuria excrete high levels of cystine in their urine and are at risk for kidney stone formation. Tiopronin is used as a second-line therapy to control the rate of cystine precipitation and excretion, and prevent kidney stone formation. It is used after a failure of the non-pharmacological first line treatment consisting of increased fluid intake, restriction of sodium and protein, and urinary alkalinization. As cystinuria is a relatively rare disease, tiopronin is classified as an orphan drug and is not patented in the United States. It is similar to d-penicillamine in use and efficacy, but offers the advantage of far less adverse effects. Tiopronin is dosed on an individual basis using close monitoring of urinary cystine concentrations and urinary output. Tiopronin may also be used to bind metal nanoparticles in Wilson's disease, which is an overload of copper in the body. It has been investigated for use in the treatment of arthritis and as a neuroprotective agent in aneurysmal subarachnoid hemorrhage.
Tiopronin is a Reducing and Complexing Thiol. The mechanism of action of tiopronin is as a Cystine Disulfide Reduction.
Tiopronin is an acylated sulfhydryl-containing derivative of glycine with reducing and complexing properties. Tiopronin breaks the disulphide bond of cystine and binds the sulfhydryl group of the resultant cysteine monomers to form a soluble tiopronin-cysteine-mixed disulfide, which is more water-soluble than cystine and is readily excreted. This leads to a reduction in urinary cystine concentration and subsequently reduces cystine stone formation.
Sulfhydryl acylated derivative of GLYCINE.

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Drug Indication
Tiopronin is indicated for the prevention of kidney stone formation in patients with severe homozygous cystinuria consisting of a urinary cystine concentration greater than 500 mg/day, and who have failed treatment with non-pharmacological measures of increased fluid intake, decreased sodium and protein intake, and urine alkalinization.

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Mechanism of Action
Kidney stones form when the solubility limit is exceeded and urine becomes supersaturated with endogenous cystine. Tiopronin is an active reducing agent which undergoes a thiol-disulfide exchange with cystine to form a water-soluble mixed disulfide complex. Thus, the amount of sparingly soluble cystine is reduced. By reducing urinary cystine concentrations below the solubility limit, tiopronin helps reduce cystine stone formation.

C5H9NO3S

163.1949

163.03

1953-02-2

Tiopronin-13C,d3;1189695-13-3;Tiopronin-d3;1189700-74-0

5483

White to off-white solid powder

1.3±0.1 g/cm3

418.3±30.0 °C at 760 mmHg

93-98 °C

206.8±24.6 °C

0.0±2.1 mmHg at 25°C

1.519

-0.33

3

4

3

10

148

0

YTGJWQPHMWSCST-UHFFFAOYSA-N

InChI=1S/C5H9NO3S/c1-3(10)5(9)6-2-4(7)8/h3,10H,2H2,1H3,(H,6,9)(H,7,8)

2-(2-sulfanylpropanoylamino)acetic acid

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)

H2O : ~100 mg/mL (~612.78 mM)
DMSO : ≥ 100 mg/mL (~612.78 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (15.32 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 (15.32 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 (15.32 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: 130 mg/mL (796.62 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.)