Tiopronin

Last updated
Tiopronin
Tiopronin.svg
Names
IUPAC name
N-(2-Sulfanylpropanoyl)glycine
Systematic IUPAC name
(2-Sulfanylpropanamido)acetic acid
Other names
2-mercaptopropionylglycine
Acadione
Identifiers
3D model (JSmol)
1859822
ChEMBL
ChemSpider
ECHA InfoCard 100.016.163 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 217-778-4
KEGG
MeSH Tiopronin
PubChem CID
RTECS number
  • MC0596500
UNII
  • InChI=1S/C5H9NO3S/c1-3(10)5(9)6-2-4(7)8/h3,10H,2H2,1H3,(H,6,9)(H,7,8) Yes check.svgY
    Key: YTGJWQPHMWSCST-UHFFFAOYSA-N Yes check.svgY
  • CC(S)C(=O)NCC(O)=O
Properties
C5H9NO3S
Molar mass 163.19 g·mol−1
AppearanceWhite, 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:
GHS-pictogram-exclam.svg
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).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)
Tiopronin
Clinical data
Trade names Thiola
License data
Identifiers
DrugBank
ChEBI
CompTox Dashboard (EPA)
ECHA InfoCard 100.016.163 OOjs UI icon edit-ltr-progressive.svg

Tiopronin, sold under the brand name Thiola, is a medication used to control the rate of cystine precipitation and excretion in the disease cystinuria. [3] [4]

Contents

It is available as a generic medication. [5] [6]

Medical uses

Tiopronin is indicated, in combination with high fluid intake, alkali, and diet modification, for the prevention of cystine stone formation in people 20 kilograms (44 lb) and greater with severe homozygous cystinuria, who are not responsive to these measures alone. [1] [2]

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. [8]

Pharmacology

Mechanism of action

Tiopronin works by reacting with urinary cysteine to form a more soluble, disulfide linked, tiopronin-cysteine complex. [8]

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. [9] [10]

In 2016 Imprimis Pharmaceuticals introduced a lower cost version marketed as a compounded drug. [11]

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, [12] [13] though tiopronin is not an anti-inflammatory.[ citation needed ]

Tiopronin is also sometimes used as a stabilizing agent for metal nanoparticles. The thiol group binds to the nanoparticles, preventing coagulation. [14]

Related Research Articles

<span class="mw-page-title-main">Cysteine</span> Proteinogenic amino acid

Cysteine is a semiessential proteinogenic amino acid with the formula HOOC−CH(−NH2)−CH2−SH. The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. Cysteine is chiral, but interestingly, both D and L-cysteine are found in nature with D-cysteine having been found in developing brain.

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<span class="mw-page-title-main">Ritonavir</span> Antiretroviral medication

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<span class="mw-page-title-main">Cystinuria</span> Amino acid metabolic disorder involving cystine stones forming in the kidneys, ureter, and bladder

Cystinuria is an inherited autosomal recessive disease characterized by high concentrations of the amino acid cystine in the urine, leading to the formation of cystine stones in the kidneys, ureters, and bladder. It is a type of aminoaciduria. "Cystine", not "cysteine," is implicated in this disease; the former is a dimer of the latter.

<span class="mw-page-title-main">Sulfasalazine</span> Chemical compound

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<span class="mw-page-title-main">Penicillamine</span> Chemical compound

Penicillamine, sold under the brand name of Cuprimine among others, is a medication primarily used for the treatment of Wilson's disease. It is also used for people with kidney stones who have high urine cystine levels, rheumatoid arthritis, and various heavy metal poisonings. It is taken by mouth.

<span class="mw-page-title-main">Hydroxychloroquine</span> Antimalarial medication

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References

  1. 1 2 "Thiola- tiopronin tablet, sugar coated". DailyMed. Retrieved 18 June 2021.
  2. 1 2 "Thiola EC- tiopronin tablet, delayed release". DailyMed. 15 March 2021. Retrieved 6 March 2023.
  3. 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.
  4. 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.
  5. "Competitive Generic Therapy Approvals". U.S. Food and Drug Administration (FDA). 29 June 2023. Archived from the original on 29 June 2023. Retrieved 29 June 2023.
  6. "First Generic Drug Approvals 2023". U.S. Food and Drug Administration (FDA). 30 May 2023. Archived from the original on 30 June 2023. Retrieved 30 June 2023.
  7. 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.
  8. 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.
  9. Lowe D (11 September 2014). "The Most Unconscionable Drug Price Hike I Have Yet Seen". In the Pipeline.
  10. Carroll J (September 20, 2015). "Why would Martin Shkreli hike an old drug price by 5000%? Only a 'moron' would ask". FierceBiotech.
  11. Elvidge S (September 29, 2016). "Imprimis shuts down Texas plant, axes 8% of jobs". BioPharma Dive.
  12. 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.
  13. 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.
  14. 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.