Cystamine dihydrochloride

Cystamine (dihydrochloride) is the disulfide form of the free thiol, cysteamine. Cystamine is an orally active transglutaminase (Tgase) inhibitor. Cystamine also has inhibition activity for caspase-3 with an IC50 value of 23.6 μM. Cystamine can be used for the research of severals diseases including Huntington's disease (HD) [1][2][3].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Apoptosis >> Caspase

Research Areas >> Neurological Disease

Caspase 3:23.6 μM (IC50)

Cystamine (dihydrochloride) has inhibition activity for caspase-3 with an IC50 value of 23.6 μM[1]. Cystamine (0-500 μM; 0-16 h) inhibits recombinant active caspase-3 in a concentration-dependent manner[1]. Cystamine (250 μM; 10 h) robustly increases the levels of glutathione[1]. Western Blot Analysis[1] Cell Line: Human neuroblastoma SH-SY5Y cells Concentration: 250, 500 μM Incubation Time: 0-16 h Result: Inhibited the MG132-mediated activation of caspase-3. Inhibited the H2O2-mediated activation of caspase-3. Inhibited caspase-3 activity in a tTG-independent manner.

Cystamine (dihydrochloride) (oral, i.p.; 112, 225 mg/kg) reduces Tgase activity and GGEL levels, lessens the behavioral and neuropathological severity, and extends survival in R6/2 transgenic HD mice[2]. Animal Model: R6/2 transgenic HD mice[2] Dosage: 112, 225 mg/kg Administration: Intraperitoneal or oral, daily Result: Significantly extended survival, improved body weight and motor performance, delayed the neuropathological sequela and significantly altered the levels of Tgase activity and N(Sigma)-(gamma-L-glutamyl)-L-lysine (GGEL) levels.

MOLECULAR FORMULA :

C4-H12-N2-S2.2Cl-H

MOLECULAR WEIGHT :

225.22

WISWESSER LINE NOTATION :

Z2SS2Z

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

896 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

TOVEFN Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown Volume(issue)/page/year: (3),46,1994

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

200 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

AEPPAE Naunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie und Pharmakologie. (Berlin, Ger.) V.110-253, 1925-66. For publisher information, see NSAPCC. Volume(issue)/page/year: 185,461,1937

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

874 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

TOVEFN Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown Volume(issue)/page/year: (3),46,1994

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

405 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 21,284,1971

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

200 mg/kg

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - other changes

REFERENCE :

AEPPAE Naunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie und Pharmakologie. (Berlin, Ger.) V.110-253, 1925-66. For publisher information, see NSAPCC. Volume(issue)/page/year: 185,461,1937

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

300 mg/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - spastic paralysis with or without sensory change Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :

AEPPAE Naunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie und Pharmakologie. (Berlin, Ger.) V.110-253, 1925-66. For publisher information, see NSAPCC. Volume(issue)/page/year: 185,461,1937 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1250 mg/kg

SEX/DURATION :

female 13-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

REFERENCE :

JEEMAF Journal of Embryology and Experimental Morphology. (Essex, UK) V.1-98, 1953-86. For Publisher information, see DEVPED Volume(issue)/page/year: 8,94,1960 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5832 No. of Facilities: 7 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 1822 (estimated) No. of Female Employees: 272 (estimated)