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
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
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)
  • US: C (Risk not ruled out)
    Legal status
    Hazards
    GHS pictograms
    GHS Signal word Warning
    GHS 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

    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 100mg 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.
    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.
    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.
    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.
    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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