Tiopronin

Tiopronin (trade name Thiola) is a prescription thiol drug used to control the rate of cystine precipitation and excretion in the disease cystinuria.[1][2] 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
IUPAC name
2-(2-sulfanylpropanoylamino)acetic acid
Other names
2-mercaptopropionylglycine
Acadione
Thiola
Identifiers
3D model (JSmol)
1859822
ChEMBL
ChemSpider
ECHA InfoCard 100.016.163
EC Number
  • 217-778-4
KEGG
MeSH Tiopronin
RTECS number
  • MC0596500
UNII
Properties
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)
Legal status
Hazards
GHS pictograms
GHS Signal word Warning
H302
Lethal dose or concentration (LD, LC):
1,300 mg kg−1 (oral, rat)
Related compounds
Related alkanoic acids
Related compounds
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

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.[3]

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,[4][5] 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.[6]

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.[7] Its pharmacokinetics have been studied.[3]

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.[8][9]

In 2016 Imprimis Pharmaceuticals introduced a lower cost version marketed as a compounded drug.[10]

References
  1. Lindell, Å.; Denneberg, T.; Hellgren, E.; Jeppsson, J. -O.; Tiselius, H. -G. (1995). "Clinical course and cystine stone formation during tiopronin treatment". Urological Research. 23 (2): 111–117. doi:10.1007/BF00307941. PMID 7676533. S2CID 34308815.
  2. Coe, Fredric L.; Parks, Joan H.; Asplin, John R. (15 October 1992). "The Pathogenesis and Treatment of Kidney Stones". New England Journal of Medicine. 327 (16): 1141–1152. doi:10.1056/NEJM199210153271607. PMID 1528210.
  3. Carlsson, M. S.; Denneberg, T.; Emanuelsson, B.-M.; 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.
  4. Delecoeuillerie, G (30 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.
  5. Pasero, Giampiero; Pellegrini, Pietro; Ambanelli, Umberto; Ciompi, Maria Laura; Colamussi, Vincenzo; Ferraccioli, Gianfranco; Barbieri, Paola; Mazzoni, Maria Rosa; Menegale, Germano; Trippi, Donatella (August 1982). "Controlled multicenter trial of tiopronin and D-penicillamine for rheumatoid arthritis". Arthritis & Rheumatism. 25 (8): 923–929. doi:10.1002/art.1780250803. PMID 7115451.
  6. Jennifer A. Dahl; Bettye L. S. Maddux & James E. Hutchison (2007). "Toward Greener Nanosynthesis". Chemical Reviews. 107 (6): 2228–2269. CiteSeerX 10.1.1.454.2724. doi:10.1021/cr050943k. PMID 17564480.
  7. Jaffe, Israeli A. (March 1986). "Adverse effects profile of sulfhydryl compounds in man". The American Journal of Medicine. 80 (3): 471–476. doi:10.1016/0002-9343(86)90722-9. PMID 2937293.
  8. Lowe, Derek (11 September 2014). "The Most Unconscionable Drug Price Hike I Have Yet Seen". In the Pipeline.
  9. Carroll, John (September 20, 2015). "Why would Martin Shkreli hike an old drug price by 5000%? Only a 'moron' would ask". FierceBiotech.
  10. Elvidge, Suzanne (September 29, 2016). "Imprimis shuts down Texas plant, axes 8% of jobs". BioPharma Dive.
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