TIOPRONIN ARGININE

Details

Stereochemistry	EPIMERIC
Molecular Formula	C6H14N4O2.C5H9NO3S
Molecular Weight	337.396
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(S)C(=O)NCC(O)=O.N[C@@H](CCCNC(N)=N)C(O)=O

InChI

InChIKey=CFAXANACVDYTPS-WCCKRBBISA-N

InChI=1S/C6H14N4O2.C5H9NO3S/c7-4(5(11)12)2-1-3-10-6(8)9;1-3(10)5(9)6-2-4(7)8/h4H,1-3,7H2,(H,11,12)(H4,8,9,10);3,10H,2H2,1H3,(H,6,9)(H,7,8)/t4-;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=494a714e-923c-cd57-df6c-12886afb265a
Curator's Comment: description was created based on several sources, including: http://www.drugbank.ca/drugs/DB06823 https://en.wikipedia.org/wiki/Tiopronin

Tiopronin is a prescription thiol drug used primarily in the treatment of severe homozygous cystinuria. Patients with cystinuria excrete high levels of cystine in their urine and are at risk for kidney stone formation. Tiopronin is used as a second-line therapy to control the rate of cystine precipitation and excretion, and prevent kidney stone formation. It is used after a failure of the non-pharmacological first line treatment consisting of increased fluid intake, restriction of sodium and protein, and urinary alkalinization. As cystinuria is a relatively rare disease, tiopronin is classified as an orphan drug and is not patented in the United States. It is similar to d-penicillamine in use and efficacy, but offers the advantage of far less adverse effects. Tiopronin is dosed on an individual basis using close monitoring of urinary cystine concentrations and urinary output. Tiopronin is a chelating agent. It works by removing extra cystine (the cause of kidney stones) from the urine, which keeps the kidney stones from forming. It works by reacting with urinary cysteine to form a more soluble, disulfide linked, tiopronin-cysteine complex.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
CHEMBL590540: CYSTINE 3 Target ID: CHEMBL590540: CYSTINE Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=494a714e-923c-cd57-df6c-12886afb265a	Chelating Agent 142

Conditions

Condition	Modality	Targets	Highest Phase	Product
Homozygous cystinuria 3 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=494a714e-923c-cd57-df6c-12886afb265a	Primary		Approved 8429	THIOLA Approved Use Tiopronin Launch Date 1988

C_max

Value	Dose	Co-administered	Analyte	Population
3.6 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1505618	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		TIOPRONIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
29 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1505618	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		TIOPRONIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
18.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1505618	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		TIOPRONIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1 g 3 times / day multiple, oral Highest studied dose Dose: 1 g, 3 times / day Route: oral Route: multiple Dose: 1 g, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20559104/	unhealthy, 43-74 n = 9 Health Status: unhealthy Condition: aneurysmal subarachnoid hemorrhage Age Group: 43-74 Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/20559104/	Sources: https://pubmed.ncbi.nlm.nih.gov/20559104/
1 g 1 times / day multiple, oral Highest studied dose Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7115451/	unhealthy, 56.7 n = 28 Health Status: unhealthy Condition: rheumatoid arthritis Age Group: 56.7 Sex: M+F Population Size: 28 Sources: https://pubmed.ncbi.nlm.nih.gov/7115451/	Other AEs: Proteinuria, Stomatitis... Other AEs: Proteinuria (4 patients) Stomatitis (3 patients) Itching (2 patients) Discomfort epigastric (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/7115451/
0.267 g 3 times / day multiple, oral Recommended Dose: 0.267 g, 3 times / day Route: oral Route: multiple Dose: 0.267 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211843s000lbl.pdf	unhealthy n = 17 Health Status: unhealthy Condition: cystinuria Population Size: 17 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211843s000lbl.pdf	Other AEs: Anemia, Nausea... Other AEs: Anemia (6%) Nausea (12%) Emesis Diarrhea (6%) Abdominal pain (6%) Oral ulceration (18%) Fever Weakness (12%) Fatigue Edema peripheral (6%) Chest pain (6%) Anorexia Arthralgia (12%) Proteinuria (6%) Impotence (6%) Cough (6%) Rash (12%) Ecchymosis Pruritus (6%) Urticaria Skin wrinkling (6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211843s000lbl.pdf
0.267 g 3 times / day multiple, oral Recommended Dose: 0.267 g, 3 times / day Route: oral Route: multiple Dose: 0.267 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211843s000lbl.pdf	unhealthy n = 49 Health Status: unhealthy Condition: cystinuria Population Size: 49 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211843s000lbl.pdf	Other AEs: Anemia, Nausea... Other AEs: Anemia (2%) Nausea (25%) Emesis (10%) Diarrhea (18%) Abdominal pain Oral ulceration (12%) Fever (8%) Weakness (4%) Fatigue (14%) Edema peripheral (6%) Chest pain Anorexia (8%) Arthralgia Proteinuria (10%) Impotence Cough Rash (14%) Ecchymosis (6%) Pruritus (4%) Urticaria (8%) Skin wrinkling (6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211843s000lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	OAT3 339

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
MRP1 172	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/21657271/	yes
P-gp 1650	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/21657271/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
OAT3 339	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24627218/	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY536622	https://www.001chemical.com/chem/1953-02-2
3B Scientific (Wuhan) Corp	3B2-0198	http://www.3bsc.com/index/pro_info.php?id=19554
AA Blocks	AA0035MI	https://www.aablocks.com/goods/Goods/detail?id=AA0035MI
AHH Chemical co.,ltd	MT-59530	http://www.ahhchemical.com/product/MT-59530.html
AK Scientific, Inc. (AKSCI)	70454	http://www.aksci.com/item_detail.php?cat=70454
Aaron Chemicals	AR0036EA	http://www.aaronchem.com/1953-02-2
AbMole Bioscience	M6015	http://www.abmole.com/products/tiopronin.html
Acadechem	ACDS-027577	http://www.acadechemical.com/product/102276
Accela ChemBio Inc	SY262996	http://www.accelachem.com/cn/search.html?keyword=SY262996&attname=GoodsCode
Achemo Scientific Limited	AC-11491	http://www.achemo.com/product_view.asp?ID=1381
Allbio Pharm Co., Ltd	AD08526	http://www.allbiopharm.com/product/n/AD08526
Angene	AGN-PC-07A27E	http://www.angenechemical.com/productshow/AGN-PC-07A27E.html
Anward	ANW-41587	http://www.anward.com/pro_result/26370
Ark Pharm	AK501603	http://www.arkpharminc.com/products/1953-02-2.html
BLD Pharm	BD2874	http://www.bldpharm.com/products/1953-02-2.html
BioChemPartner	BCP13354	http://www.biochempartner.com/1953-02-2-BCP13354
BioCrick	BCC3870	http://www.biocrick.com/Tiopronin-Thiola-BCC3870.html
BioSynth	J-012651	https://www.biosynth.com/en/products/all-products/products/J-012651.html
CSNpharm	CSN13774	https://www.csnpharm.com/products/tiopronin.html
Capot Chemical	15029	http://www.capotchem.com/en/15029.htm
Capot Chemical	PubChem15029	http://www.capotchem.com/en/15029.htm
Chem Scene	CS-2431	http://www.chemscene.com/1953-02-2.html
ChemFish Tokyo co.,ltd	5483	http://www.chemfish.co.jp/index.php?id=4620&project=product
ChemMol	30104676	http://www.chemmol.com/chemmol/30104676.html
ChemMol	49408236	http://www.chemmol.com/chemmol/49408236.html
Chemspace	CSSB00000031781	https://chem-space.com/CSSB00000031781
DC Chemicals	DCAPI1105	http://www.dcchemicals.com//product_show-Tiopronin_Thiola_.html
Finetech	FT-0603530	http://www.finetechnology-ind.com/prod/detail/pub/1953-02-2.html
Finetech	FT-0653686	http://www.finetechnology-ind.com/prod/detail/pub/1953-02-2.html
Glentham Life Sciences	GM4146	http://www.glentham.com/products/product/GM4146/
Hairui	HR137424	http://www.hairuichem.com/en/product/1953-02-2.html
LGC Standards	DRE-C17587000	https://www.lgcstandards.com/US/en/p/DRE-C17587000
Lab Network	LN01300535	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01300535
MedChem Express	HY-B0373	https://www.medchemexpress.com/Tiopronin.html
Molcore	MC536622	https://www.molcore.com/product/1953-02-2
MuseChem	A000514	https://www.musechem.com/product/A000514.html
OChem	5409	http://www.ocheminc.com/index.php?act=psearch&pid=953T022
Oakwood	99155	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=162585&ExtHyperLink=1
Sigma-Aldrich	280968_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/280968?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	33986_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/33986?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	M6635_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/m6635?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sinfoo Biotech	S011920	http://www.sinfoobiotech.com/product/1015318
Smolecule	S545402	http://www.smolecule.com/products/s545402
Smolecule	S793344	https://www.smolecule.com/products/s793344
TCI (Tokyo Chemical Industry)	T2614	http://www.tcichemicals.com/eshop/en/us/commodity/T2614/index.html
THE BioTek	bt-285718	https://www.thebiotek.com/product/inhibitors/bt-285718
Yuhao Chemical	SY0182	http://www.chemyuhao.com/1953-2-2.html
abcr GmbH	AB261737	http://www.abcr.com/shop/en/AB261737
eNovation Chemicals	D671098	https://www.enovationchem.com/ProductDetails.asp?ProductID=D671098
mcule	MCULE-8593628629	https://mcule.com/MCULE-8593628629/

PubMed

Title	Date	PubMed
Attenuation of the acute adriamycin-induced cardiac and hepatic oxidative toxicity by N-(2-mercaptopropionyl) glycine in rats.	2001 Nov	11767415
Cystine analyses of separate day and night urine as a basis for the management of patients with homozygous cystinuria.	2001 Oct	11762791
A comparison of the effects of potassium citrate and sodium bicarbonate in the alkalinization of urine in homozygous cystinuria.	2001 Oct	11762790
Evaluation of genotoxic and cytotoxic potential of thiola (N-2-mercaptopropionylglycine), a medicine used in the treatment of humans contaminated with mercury.	2002	11813292
Effect of treatment on ventricular function and troponin I proteolysis in reperfused myocardium.	2002 Apr	11991730
Isoflurane preconditions myocardium against infarction via release of free radicals.	2002 Apr	11964602
The relative order of mK(ATP) channels, free radicals and p38 MAPK in preconditioning's protective pathway in rat heart.	2002 Aug 15	12160965
Acetylcholine leads to free radical production dependent on K(ATP) channels, G(i) proteins, phosphatidylinositol 3-kinase and tyrosine kinase.	2002 Aug 15	12160951
Mechanism of preconditioning by isoflurane in rabbits: a direct role for reactive oxygen species.	2002 Dec	12459675
Oxidant species trigger late preconditioning against myocardial stunning in conscious rabbits.	2002 Jan	11748073
Blockade of angiotensin II type 1 receptors suppressed free radical production and preserved coronary endothelial function in the rabbit heart after myocardial infarction.	2002 Jan	11743227
Yellow nail syndrome associated with thiol compound therapy for rheumatoid arthritis. Two case reports.	2002 Jun	12184439
Oxygen radicals trigger activation of NF-kappaB and AP-1 and upregulation of ICAM-1 in reperfused canine heart.	2002 May	11959643
Glyceraldehyde phosphate dehydrogenase oxidation during cardiac ischemia and reperfusion.	2002 Nov	12431453
Infarct size limitation by nicorandil: roles of mitochondrial K(ATP) channels, sarcolemmal K(ATP) channels, and protein kinase C.	2002 Oct 16	12392845
The new MATH: homology suggests shared binding surfaces in meprin tetramers and TRAF trimers.	2002 Oct 23	12387856
[Insulin autoimmune syndrome].	2002 Sep	12387090
Meprin proteolytic complexes at the cell surface and in extracellular spaces.	2003	14587282
Enhancement of antiradiation potential of some aminothiols by beta-carotene.	2003	12743471
Mitochondrial adenosine triphosphate-regulated potassium channel opening acts as a trigger for isoflurane-induced preconditioning by generating reactive oxygen species.	2003 Apr	12657856
3-Aminopropanal, formed during cerebral ischaemia, is a potent lysosomotropic neurotoxin.	2003 Apr 15	12513695
Urinary excretion of total cystine and the dibasic amino acids arginine, lysine and ornithine in relation to genetic findings in patients with cystinuria treated with sulfhydryl compounds.	2003 Dec	14586528
Au nanoparticle-enhanced surface plasmon resonance sensing of biocatalytic transformations.	2003 Dec 15	14679522
Involvement of reactive oxygen species in cardiac preconditioning in rats.	2003 Feb	12626123
Effects of N-(2-mercaptopropionyl)-glycine on mitochondrial function in ischemic-reperfused heart.	2003 Feb	12566114
The cardioprotective and mitochondrial depolarising properties of exogenous nitric oxide in mouse heart.	2003 Feb	12566113
Possible underlying mechanism for hydrogen peroxide-induced electromechanical suppression in human atrial myocardium.	2003 Jan	12686731
Effects of sulfhydryl compounds on pancreatic cytoprotection in acute necrotic pancreatitis.	2003 Jan	12667389
Paradoxical effects of thiol reagents on Jurkat cells and a new thiol-sensitive mutant form of human mitochondrial superoxide dismutase.	2003 Jan 1	12517793
Modifications of myosin-regulatory light chain correlate with function of stunned myocardium.	2003 Jul	12818574
Adenosine and opioid receptor-mediated cardioprotection in the rat: evidence for cross-talk between receptors.	2003 Jul	12637353
Protective effect of N2-mercaptopropionylglycine on rats and dogs liver during ischemia/reperfusion process.	2003 Jul-Sep	15029394
Oxygen dependency of the adrenergic Na/H exchange in rainbow trout erythrocytes is diminished by a hydroxyl radical scavenger.	2003 Jun	12780389
[Cystinuria - Cystine Stones: Recommendations for Diagnosis, Therapy and Follow-up].	2003 Mar	14566692
Cardiac ischemia causes inhibition of the Na/K ATPase by a labile cytosolic compound whose production is linked to oxidant stress.	2003 Mar 15	12650882
The cardioprotective effect of sevoflurane depends on protein kinase C activation, opening of mitochondrial K(+)(ATP) channels, and the production of reactive oxygen species.	2003 Nov	14570654
Polyherbal extract of septilin protects mice against whole body lethal dose of gamma radiation.	2004 Aug	15476309
Yellow nail syndrome in rheumatoid arthritis: a drug-induced disease?	2004 Aug	15293107
Transport of meprin subunits through the secretory pathway: role of the transmembrane and cytoplasmic domains and oligomerization.	2004 Aug 13	15187079
Delayed ischemic preconditioning activates nuclear-encoded electron-transfer-chain gene expression in parallel with enhanced postanoxic mitochondrial respiratory recovery.	2004 Aug 3	15277332
Delayed cardioprotection is mediated via a non-peptide delta opioid agonist, SNC-121, independent of opioid receptor stimulation.	2004 Jan	14685704
Oligonucleotide-displaced organic monolayer-protected silver nanoparticles and enhanced luminescence of their salted aggregates.	2004 Jul 1	15183765
Reactive oxygen species precede protein kinase C-delta activation independent of adenosine triphosphate-sensitive mitochondrial channel opening in sevoflurane-induced cardioprotection.	2004 Mar	15108962
Evidence of myofibrillar protein oxidation induced by postischemic reperfusion in isolated rat hearts.	2004 Mar	14766672
The effects of ionizing radiation on DNA: the role of thiols as radioprotectors.	2004 Mar 26	14998719
Protective effects of alpha-tocopherol and tiopronin against cisplatin-induced ototoxicity.	2004 May	15224867
Effect of change in cellular GSH levels on mitochondrial damage and cell viability loss due to mitomycin c in small cell lung cancer cells.	2004 Nov 1	15450951
HPLC study of tyrosinase inhibition by thiopronine.	2004 Sep	15340968
Complexation of polysaccharide and monosaccharide with thiolate boronic acid capped on silver nanoparticle.	2004 Sep 15	15325293
Nanoparticles comprising a mixed monolayer for specific bindings with biomolecules.	2004 Sep 29	15382939

Patents

Sample Use Guides

In Vivo Use Guide

THIOLA (Tiopronin) may be begun at a dosage of 800 mg/day in adult patients with cystine stones. In a multiclinic trial, average dose of THIOLA was about 1000 mg/day. In children, initial dosage may be based on 15 mg/kg/day. Whenever possible, THIOLA should be given in divided doses 3 times/day at least one hour before or 2 hours after meals.

Route of Administration: Oral

In Vitro Use Guide

Tiopronin (2 mM) completely prevents the Cisplatin-induced increase in enzyme leakage and substantially blocks the decrease of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction caused by Cisplatin. Tiopronin also significantly protects the renal slices from cisplatin-induced toxic effects. Tiopronin protects against cisplatin-induced nephrotoxicity by acting as an alternative target for Cisplatin both intra- and extracellularly and thus protects against cisplatin-induced depletion of glutathione in the kidney cell

Name

Type

Language

TIOPRONIN ARGININE

Common Name

English

ARGININE TIOPRONINE

Common Name

English

L-ARGININE, COMPD. WITH N-(2-MERCAPTO-1-OXOPROPYL)GLYCINE (1:1)

Systematic Name

English

GLYCINE, N-(2-MERCAPTO-1-OXOPROPYL)-, COMPD. WITH L-ARGININE (1:1)

Systematic Name

English

Arginine tiopronine [WHO-DD]

Common Name

English

ARGININE TIOPRONIN

Common Name

English

Code System Code Type Description

FDA UNII

306C40V64U