Tiopronin

Tiopronin
Names
Preferred IUPAC name
(2-Sulfanylpropanamido)acetic acid
Other names
2-mercaptopropionylglycine
Acadione
Identifiers
CAS Number
3D model (JSmol)
Beilstein Reference
 1859822
ChEMBL
ChemSpider
ECHA InfoCard 100.016.163
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EC Number
  • 217-778-4
KEGG
MeSH Tiopronin
PubChem CID
RTECS number
  • MC0596500
UNII
InChI
  • InChI=1S/C5H9NO3S/c1-3(10)5(9)6-2-4(7)8/h3,10H,2H2,1H3,(H,6,9)(H,7,8) checkY
    Key: YTGJWQPHMWSCST-UHFFFAOYSA-N checkY
SMILES
  • CC(S)C(=O)NCC(O)=O
Properties
Chemical formula
 C5H9NO3S
Molar mass 163.19 g·mol−1
Appearance White, opaque crystals
Melting point 93 to 98 °C (199 to 208 °F; 366 to 371 K)
log P −0.674
Acidity (pKa) 3.356
Basicity (pKb) 10.641
Pharmacology
G04BX16 (WHO) QG04BX16 (WHO)
By mouth
Legal status
Hazards
GHS labelling:
Pictograms
Signal word
 Warning
Hazard statements
 H302
Lethal dose or concentration (LD, LC):
1,300 mg kg−1 (oral, rat)
Related compounds
Related alkanoic acids
  • Acetylcysteine
  • Glycylglycine
  • Iminodiacetic acid
  • Nitrilotriacetic acid
  • N-Oxalylglycine
  • Bucillamine
  • Oxalyldiaminopropionic acid
  • gamma-Glutamylcysteine
Related compounds
  • N-Acetylglycinamide
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references
Tiopronin
Clinical data
Trade namesThiola
License data
Identifiers
DrugBank
ChEBI
CompTox Dashboard (EPA)
ECHA InfoCard100.016.163
Edit this at Wikidata

Tiopronin, sold under the brand name Thiola, is a medication used to control the rate of cystine precipitation and excretion in the disease cystinuria.[2][3] Due to the rarity of the disorder, tiopronin falls under the classification of an orphan drug. It is somewhat similar to penicillamine in both chemistry and pharmacology.

A generic version of tiopronin is available in the United States as of April 2021.[4]

Uses

Tiopronin is used primarily for cystinuria and is well known in the cystinuric community. Depending on the severity of a person's cystinuria, tiopronin may be taken for life, possibly starting in early childhood. The drug works by reacting with urinary cysteine to form a more soluble, disulfide linked, tiopronin-cysteine complex.[5]

Side effects

Tiopronin may present a variety of side effects, which are broadly similar to those of D-penicillamine and other compounds containing active sulfhydryl groups.[6] Its pharmacokinetics have been studied.[5]

Society and culture

In the U.S., the drug was marketed by Mission Pharmacal at $1.50 per pill, but in 2014 the rights were bought by Retrophin, owned by Martin Shkreli, and the price increased to $30 per pill for a 100 mg capsule.[7][8]

In 2016 Imprimis Pharmaceuticals introduced a lower cost version marketed as a compounded drug.[9]

Research

It may also be used for Wilson's disease (an overload of copper in the body), and has also been investigated for the treatment of arthritis,[10][11] though tiopronin is not an anti-inflammatory.

Tiopronin is also sometimes used as a stabilizing agent for metal nanoparticles. The thiol group binds to the nanoparticles, preventing coagulation.[12]

References

  1. ↑ "Thiola- tiopronin tablet, sugar coated". DailyMed. Retrieved 18 June 2021.
  2. ↑ Lindell A, Denneberg T, Hellgren E, Jeppsson JO, Tiselius HG (1995). "Clinical course and cystine stone formation during tiopronin treatment". Urological Research. 23 (2): 111–7. doi:10.1007/BF00307941. PMID 7676533. S2CID 34308815.
  3. ↑ Coe FL, Parks JH, Asplin JR (October 1992). "The pathogenesis and treatment of kidney stones". The New England Journal of Medicine. 327 (16): 1141–52. doi:10.1056/NEJM199210153271607. PMID 1528210.
  4. ↑ "Tiopronin: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 18 June 2021.
  5. 1 2 Carlsson MS, Denneberg T, Emanuelsson BM, Kågedal B, Lindgren S (August 1993). "Pharmacokinetics of oral tiopronin". European Journal of Clinical Pharmacology. 45 (1): 79–84. doi:10.1007/BF00315354. PMID 8405034. S2CID 8879752.
  6. ↑ Jaffe IA (March 1986). "Adverse effects profile of sulfhydryl compounds in man". The American Journal of Medicine. 80 (3): 471–6. doi:10.1016/0002-9343(86)90722-9. PMID 2937293.
  7. ↑ Lowe D (11 September 2014). "The Most Unconscionable Drug Price Hike I Have Yet Seen". In the Pipeline.
  8. ↑ Carroll J (September 20, 2015). "Why would Martin Shkreli hike an old drug price by 5000%? Only a 'moron' would ask". FierceBiotech.
  9. ↑ Elvidge S (September 29, 2016). "Imprimis shuts down Texas plant, axes 8% of jobs". BioPharma Dive.
  10. ↑ Delecoeuillerie G (April 1989). "[Tolerability and therapeutic maintenance of tiopronin, new basic treatment of rheumatoid arthritis. Apropos of long-term follow-up of 268 cases]". Revue du Rhumatisme et des Maladies Osteo-Articulaires. 56 (5 Pt 2): 38–42. PMID 2740804.
  11. ↑ Pasero G, Pellegrini P, Ambanelli U, Ciompi ML, Colamussi V, Ferraccioli G, et al. (August 1982). "Controlled multicenter trial of tiopronin and d-penicillamine for rheumatoid arthritis". Arthritis and Rheumatism. 25 (8): 923–9. doi:10.1002/art.1780250803. PMID 7115451.
  12. ↑ Dahl JA, Maddux BL, Hutchison JE (June 2007). "Toward greener nanosynthesis". Chemical Reviews. 107 (6): 2228–69. CiteSeerX 10.1.1.454.2724. doi:10.1021/cr050943k. PMID 17564480.
  • "Tiopronin". Drug Information Portal. U.S. National Library of Medicine.
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