Tiopronin

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.

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
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) Y
    Key: YTGJWQPHMWSCST-UHFFFAOYSA-N Y
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).
Y verify (what is YN ?)
Infobox references
Tiopronin
Clinical data
Trade namesThiola
License data
Identifiers
DrugBank
ChEBI
CompTox Dashboard (EPA)
ECHA InfoCard100.016.163

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. 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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