Tiopronin

Tiopronin
Names
	IUPAC name 2-(2-sulfanylpropanoylamino)acetic acid
	Other names 2-mercaptopropionylglycine ; Acadione ; Thiola
Identifiers
CAS Number	1953-02-2 ; 29335-92-0 R ;
3D model (JSmol)	Interactive image;
Beilstein Reference	1859822
ChEMBL	ChEMBL1314 ;
ChemSpider	5283 ; 180938 R ; 643292 S ;
ECHA InfoCard	100.016.163
EC Number	217-778-4;
KEGG	D01430 ;
MeSH	Tiopronin
PubChem CID	5483; 208825 R; 736152 S;
RTECS number	MC0596500;
UNII	C5W04GO61S ;
CompTox Dashboard (EPA)	DTXSID4023678 ;
	InChI InChI=1S/C5H9NO3S/c1-3(10)5(9)6-2-4(7)8/h3,10H,2H2,1H3,(H,6,9)(H,7,8) Key: YTGJWQPHMWSCST-UHFFFAOYSA-N ;
	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
ATC code	G04BX16 (WHO)
Legal status	US: ℞-only;
Hazards
	GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H302
	Lethal dose or concentration (LD, LC):
LD50 (median dose)	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). verify (what is ?) Infobox references

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.

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

^ 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.
^ 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.
^ ^a ^b 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.
^ 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.
^ 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.
^ Jennifer A. Dahl; Bettye L. S. Maddux; James E. Hutchison (2007). "Toward Greener Nanosynthesis". Chemical Reviews. 107 (6): 2228–2269. doi:10.1021/cr050943k. PMID 17564480. {{cite journal}}: Unknown parameter |last-author-amp= ignored (|name-list-style= suggested) (help)
^ 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.
^ Lowe, Derek (11 September 2014). "The Most Unconscionable Drug Price Hike I Have Yet Seen". In the Pipeline.
^ Carroll, John (September 20, 2015). "Why would Martin Shkreli hike an old drug price by 5000%? Only a 'moron' would ask". FierceBiotech.
^ Elvidge, Suzanne (September 29, 2016). "Imprimis shuts down Texas plant, axes 8% of jobs". BioPharma Dive.

External links

[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.

[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.

[Carlsson-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. doi:10.1021/cr050943k. PMID 17564480. {{cite journal}}: Unknown parameter |last-author-amp= ignored (|name-list-style= suggested) (help)

[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.

[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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