Tiopronin

Tiopronin

Tiopronin
Skeletal formula of tiopronin
Names
IUPAC name
2-(2-sulfanylpropanoylamino)acetic acid
Other names
2-mercaptopropionylglycine
Acadione
Thiola
Identifiers
 Y
R Y
ATC code R05
QG04
1859822
ChEMBL  Y
ChemSpider  Y
R Y
S Y
EC number 217-778-4
Jmol-3D images Image
Image
KEGG  Y
MeSH
PubChem
 R
 S
RTECS number MC0596500
UNII  Y
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
Legal status
  • US: C (Risk not ruled out)
Hazards
GHS pictograms The exclamation-mark pictogram in the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)
GHS signal word WARNING
H302
Harmful Xn
R-phrases R22
S-phrases S36/37
Lethal dose or concentration (LD, LC):
LD50 (Median dose)
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).
 Y  (: Y/N?)

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.

Contents

  • Uses 1
  • Side effects 2
  • Costs 3
  • References 4
  • External links 5

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 pharmokinetics have been studied.[3]

Costs

In the U.S., the drug was marketed by Mission Pharmacal at $1.50 per pill, but the rights were bought by Retrophin, owned by Martin Shkreli, and the price increased to $30 per pill.[8][9][10]

References

  1. ^ Lindell, Å.; Denneberg, T.; Hellgren, E.; Jeppsson, J. -O.; Tiselius, H. -G. "Clinical course and cystine stone formation during tiopronin treatment". Urological Research 23 (2): 111–117.  
  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.  
  3. ^ a b Carlsson, M. S.; Denneberg, T.; Emanuelsson, B.-M.; K�gedal, B.; Lindgren, S. (August 1993). "Pharmacokinetics of oral tiopronin". European Journal of Clinical Pharmacology 45 (1): 79–84.  
  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.  
  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.  
  6. ^ Jennifer A. Dahl, Bettye L. S. Maddux, and James E. Hutchison (2007). "Toward Greener Nanosynthesis". Chemical Reviews 107 (6): 2228–2269.  
  7. ^ Jaffe, Israeli A. (March 1986). "Adverse effects profile of sulfhydryl compounds in man". The American Journal of Medicine 80 (3): 471–476.  
  8. ^ "The huge price hike as sales strategy, taken to extremes by Retrophin". FiercePharma. 
  9. ^ "Why would Martin Shkreli hike an old drug price by 5000%? Only a 'moron' would ask". FierceBiotech. 
  10. ^ "‘Pharma bro’ Martin Shkreli gouged kids with kidney disease before ripping off AIDS patients". rawstory.com. 

External links

  • Thiola Main Site