CYSTEAMINE BITARTRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C4H6O6.C2H7NS
Molecular Weight	227.236
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NCCS.O[C@H]([C@@H](O)C(O)=O)C(O)=O

InChI

InChIKey=NSKJTUFFDRENDM-ZVGUSBNCSA-N

InChI=1S/C4H6O6.C2H7NS/c5-1(3(7)8)2(6)4(9)10;3-1-2-4/h1-2,5-6H,(H,7,8)(H,9,10);4H,1-3H2/t1-,2-;/m1./s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/020392s010lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/6131501 | https://www.ncbi.nlm.nih.gov/pubmed/6124307 | https://www.ncbi.nlm.nih.gov/pubmed/15675041 | https://www.ncbi.nlm.nih.gov/pubmed/28384851

Cysteamine (trade name CYSTAGON) is a cystine-depleting agent indicated for the treatment of corneal cystine crystal accumulation in patients with cystinosis. Cystinosis is an autosomal recessive inborn error of metabolism in which the transport of cystine out of lysosomes is abnormal; in the nephropathic form, accumulation of cystine and formation of crystals damage various organs, especially the kidney, leading to renal tubular Fanconi Syndrome and progressive glomerular failure, with end-stage renal failure by the end of the first decade of life. In four studies of cystinosis patients before cysteamine was available, renal death (need for transplant or dialysis) occurred at the median age of fewer than 10 years. Patients with cystinosis also experience growth failure, rickets, and photophobia due to cystine deposits in the cornea. With time most organs are damaged, including the retina, muscles and central nervous system. Cysteamine is an aminothiol that participates within lysosomes in a thiol-disulfide interchange reaction converting cystine into cysteine and cysteine-cysteamine mixed disulfide, both of which can exit the lysosome in patients with cystinosis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Protein-glutamine gamma-glutamyltransferase 2 7 Target ID: P21980 Gene ID: 7052.0 Gene Symbol: TGM2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/15675041	Inhibitor 8297		178.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Nephropathic cystinosis 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/020392s010lbl.pdf	Primary		Approved 8429	CYSTAGON Approved Use PROCYSBI is indicated for the treatment of nephropathic cystinosis in adult and pediatric patients 2 years of age and older. PROCYSBI is a cystine-depleting agent indicated for the treatment of nephropathic cystinosis in adult and pediatric patients 2 years of age and older. (1) Launch Date 1994

C_max

Value	Dose	Co-administered	Analyte	Population
2.7 mg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213491s000lbl.pdf	404 mg/m² 4 times / day steady-state, oral dose: 404 mg/m² route of administration: Oral experiment type: STEADY-STATE co-administered:		CYSTEAMINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN
37.72 μM DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203389s000lbl.pdf	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:		CYSTEAMINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
351 mg × min/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213491s000lbl.pdf	404 mg/m² 4 times / day steady-state, oral dose: 404 mg/m² route of administration: Oral experiment type: STEADY-STATE co-administered:		CYSTEAMINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN
96 μM × h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203389s000lbl.pdf	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:		CYSTEAMINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
90 min DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213491s000lbl.pdf	404 mg/m² 4 times / day steady-state, oral dose: 404 mg/m² route of administration: Oral experiment type: STEADY-STATE co-administered:		CYSTEAMINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
48% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213491s000lbl.pdf	404 mg/m² 4 times / day steady-state, oral dose: 404 mg/m² route of administration: Oral experiment type: STEADY-STATE co-administered:		CYSTEAMINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN
48% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203389s000lbl.pdf	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:		CYSTEAMINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.44 % 1 times / day multiple, ophthalmic Recommended Dose: 0.44 %, 1 times / day Route: ophthalmic Route: multiple Dose: 0.44 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/200740Orig1s000MedR.pdf Page: 98 EI0109S	unhealthy, 13.4 (5.9-27.8) n = 20 Health Status: unhealthy Condition: cystinosis Age Group: 13.4 (5.9-27.8) Sex: M+F Population Size: 20 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/200740Orig1s000MedR.pdf Page: 98 EI0109S	Disc. AE: Intracranial hypertension... AEs leading to discontinuation/dose reduction: Intracranial hypertension Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/200740Orig1s000MedR.pdf Page: 98 EI0109S
600 mg 1 times / day multiple, oral Recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000MedR.pdf Page: RP103-05	healthy, 37.5 (19-64) n = 20 Health Status: healthy Age Group: 37.5 (19-64) Sex: M+F Population Size: 20 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000MedR.pdf Page: RP103-05	Disc. AE: Blurred vision, Hematuria... AEs leading to discontinuation/dose reduction: Blurred vision Hematuria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000MedR.pdf Page: RP103-05

AEs

AE	Significance	Dose	Population
Intracranial hypertension	Disc. AE	0.44 % 1 times / day multiple, ophthalmic Recommended Dose: 0.44 %, 1 times / day Route: ophthalmic Route: multiple Dose: 0.44 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/200740Orig1s000MedR.pdf Page: 98 EI0109S	unhealthy, 13.4 (5.9-27.8) n = 20 Health Status: unhealthy Condition: cystinosis Age Group: 13.4 (5.9-27.8) Sex: M+F Population Size: 20 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/200740Orig1s000MedR.pdf Page: 98 EI0109S
Blurred vision	Disc. AE	600 mg 1 times / day multiple, oral Recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000MedR.pdf Page: RP103-05	healthy, 37.5 (19-64) n = 20 Health Status: healthy Age Group: 37.5 (19-64) Sex: M+F Population Size: 20 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000MedR.pdf Page: RP103-05
Hematuria	Disc. AE	600 mg 1 times / day multiple, oral Recommended Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000MedR.pdf Page: RP103-05	healthy, 37.5 (19-64) n = 20 Health Status: healthy Age Group: 37.5 (19-64) Sex: M+F Population Size: 20 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000MedR.pdf Page: RP103-05

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587 inducer 781	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP2A6 707 P-gp 1461 BCRP 699 OATP1B1 788 OATP1B3 706 OAT1 599 OAT3 642 OCT1 512 OCT2 647	CYP1A2 1054 CYP2B6 664 CYP2C8 693 CYP2C19 991 CYP2E1 667 CYP2A6 543 P-gp 1537 BCRP 561 OATP1B1 406 OATP1B3 350 OAT1 326 OAT3 339 OCT1 327 OCT2 355	CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	inconclusive
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	inconclusive
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	inconclusive
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=20 Page: 20.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=20 Page: 20.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=20 Page: 20.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=20 Page: 20.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=20 Page: 20.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=20 Page: 20.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=20 Page: 20.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=20 Page: 20.0	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=20 Page: 20.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	weak [Inhibition 780 uM]
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	weak [Inhibition 780 uM]

Drug as victim

Target	Modality	Activity
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=16 Page: 16.0	no
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=16 Page: 16.0	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=23 Page: 23.0	no
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=23 Page: 23.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=23 Page: 23.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=23 Page: 23.0	no
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=23 Page: 23.0	no
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=16 Page: 16.0	yes
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=16 Page: 16.0	yes
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=16 Page: 16.0	yes
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=16 Page: 16.0	yes
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=16 Page: 16.0	yes
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=16 Page: 16.0	yes
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=16 Page: 16.0	yes
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=23 Page: 23.0	yes
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203389Orig1s000ClinPharmR.pdf#page=22 Page: 22.0	yes

PubMed

Title	Date	PubMed
New method for determining cystine in leukocytes and fibroblasts.	1999 Dec	10585356
Pantetheinase activity of membrane-bound Vanin-1: lack of free cysteamine in tissues of Vanin-1 deficient mice.	2000 Oct 20	11042271
Taurine and hypotaurine in spermatozoa and epididymal fluid of cats.	2001	11787195
Antioxidants suppress mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus (SLE).	2001	11341102
Structure-activity analysis of the potentiation by aminothiols of the chromosome-damaging effect of bleomycin in G0 human lymphocytes.	2001	11246218
Influence of constituent mass on secondary ion yield enhancements from polyatomic ion impacts on aminoethanethiol self-assembled monolayer surfaces.	2001	11241769
Gastrointestinal damage induced by celecoxib and rofecoxib in rats.	2001 Apr	11330413
Threonine metabolism in isolated rat hepatocytes.	2001 Dec	11701446
An electrochemical evidence of free radicals formation from flutamide and its reactivity with endo/xenobiotics of pharmacological relevance.	2001 Jan	11206916
Pharmacological properties of a newly synthesized H(+)/K(+) ATPase inhibitor, 1-(2-methyl-4-methoxyphenyl)-4-.	2001 Jan 5	11137875
Cysteamine-colon and cysteamine-duodenum lesions in rats. Attenuation by gastric pentadecapeptide BPC 157, cimetidine, ranitidine, atropine, omeprazole, sulphasalazine and methylprednisolone.	2001 Jan-Dec	11595448
Meiotic and developmental competence of prepubertal and adult swine oocytes.	2001 Jul 1	11467513
Attenuation of radiation-induced genomic instability by free radical scavengers and cellular proliferation.	2001 Jul 1	11425485
NAC/MEA conjugate: a new potent antioxidant which increases the GSH level in various cell lines.	2001 May 7	11354374
[Comparative study of the radiation-protective effectiveness of low doses of cysteamine, heparin, and naphtizine in experiments on mice].	2001 May-Jun	11458646
A novel strategy for the synthesis of neoglycoconjugates from deacylated deep rough lipopolysaccharides.	2002	12230919
The ability of hippocampal CA1 area for induction of long-term potentiation is persistently reduced by prior treatment with cysteamine: an in vitro study.	2002 Aug	12372700
In vivo confocal microscopy of the cornea in nephropathic cystinosis.	2002 Dec	12470153
Glutathione in gingival crevicular fluid and its relation to local antioxidant capacity in periodontal health and disease.	2002 Dec	12456773
Evidence for a central inhibitory role of growth hormone secretagogues and ghrelin on gastric acid secretion in conscious rats.	2002 Feb	11867937
Generating favorable nano-environments for thermal and solvent stabilization of immobilized beta-galactosidase.	2002 Feb 15	11787015
A molecular CT blood pool contrast agent.	2002 Jul	12139092
X-ray crystallographic studies on butyryl-ACP reveal flexibility of the structure around a putative acyl chain binding site.	2002 Jun	12057197
Cysteamine supplementation during in vitro maturation and embryo culture: a useful tool for increasing the efficiency of bovine in vitro embryo production.	2002 Jun	11984830
Electric potential control of DNA immobilization on gold electrode.	2003 Jan	12445444

Patents

Sample Use Guides

In Vivo Use Guide

The recommended maintenance dose of 1.30 grams/m2/day. Patients over age 12 and over 110 pounds should receive 2.0 grams/day given in four divided doses as a starting maintenance dose. This dose should be reached after 4 to 6 weeks of incremental dosage increases as stated above. The dose should be raised if the leukocyte cystine level remains > 2 nmol/1⁄2 cystine/mg/protein.

Route of Administration: Oral

In Vitro Use Guide

Oocytes were obtained from 4-6 weeks old Naval Medical Research Institute (NMRI) female mice, 48 hours after stimulation with Intraperitoneal (IP) injection of 10 IU Pregnant Mare Serum Gonadotropin (PMSG). Germinal Vesicle (GV) oocyte with and without cumulus cells were isolated from ovaries and cultured in Tissue Culture Medium (TCM) 199 with availability of 100 μM of CYS (Cysteamine). After 24 hours, mature oocyte in metaphase II (MII) were fertilized with sperm in In vitro Fertilization (IVF) medium (T6) and evaluated for fetal development into blastocyst. CYS could significantly (p<0.05) increase the rate of IVM and oocyte evolution, and embryo formation in medium culture.

Name

Type

Language

CYSTEAMINE BITARTRATE

Common Name

English

MERCAMINE BITARTRATE

Common Name

English

CYSTEAMINE BITARTRATE [ORANGE BOOK]

Common Name

English

Mercaptamine bitartrate [WHO-DD]

Common Name

English

CYSTAGON

Brand Name

English

CYSTEAMINE BITARTRATE [JAN]

Common Name

English

ETHANETHIOL, 2-AMINO-, (2R,3R)-2,3-DIHYDROXYBUTANEDIOATE (1:1)

Systematic Name

English

MERCAPTAMINE BITARTRATE [MART.]

Common Name

English

RP-103

Code

English

.BETA.-MERCAPTOETHYLAMINE HYDROGEN TARTRATE

Systematic Name

English

CYSTEAMINE BITARTRATE [MI]

Common Name

English

MERCAPTOETHYLAMINE BITARTRATE

Systematic Name

English

MERCAPTAMINE BITARTRATE

Common Name

English

CYSTEAMINE BITARTRATE [VANDF]

Common Name

English

PROCYSBI

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29701