69819-86-9

Basic information

• Product Name: Glycine, L-γ-glutaMyl-S-(diMethylarsino)-L-cysteinyl-
• Synonyms: Glycine, L-γ-glutaMyl-S-(diMethylarsino)-L-cysteinyl-;ZIO 101;Darinaparsin;Selurampanel;EOS-60608
• CAS NO: 69819-86-9
• Molecular Formula: C12H22AsN3O6S
• Molecular Weight: 411.31
• EINECS: -0
• Mol File: 69819-86-9.mol
• Article Data: 9

Chemical Properties

• Appearance: /
• PKA: 2.21±0.10(Predicted)
• CAS DataBase Reference: Glycine, L-γ-glutaMyl-S-(diMethylarsino)-L-cysteinyl-(CAS DataBase Reference)
• NIST Chemistry Reference: Glycine, L-γ-glutaMyl-S-(diMethylarsino)-L-cysteinyl-(69819-86-9)
• EPA Substance Registry System: Glycine, L-γ-glutaMyl-S-(diMethylarsino)-L-cysteinyl-(69819-86-9)

Safety Data

• Hazardous Substances Data: 69819-86-9(Hazardous Substances Data)

Usage

Description

Darinaparsin is a dimethylated arsenic linked to glutathione. It is cytotoxic to DU145, LNCaP, and PC3 prostate cancer cells (IC50s = 5-10 μM) and patient-derived primary prostate cancer cells (IC50s = 2.5-20 μM), as well as Jurkat T cell lymphoma and L540 Hodgkin lymphoma cells (IC50s = 2.7 and 1.3 μM, respectively). It decreases the tumor-initiating subpopulation in DU145 and PC3 cells and halts the cell cycle in the G2/M phase. Darinaparsin decreases transcription of Gli-2, a transcription factor that mediates Sonic hedgehog signaling, when used at a concentration of 1.5 but not 3 μM. It decreases SHP1 phosphatase activity and increases ERK phosphorylation. Darinaparsin reduces tumor growth in DU145 and PC3 prostate cancer mouse xenograft models when administered at a dose of 100 mg/kg every other day.

Upstream product

• 70-18-8 GLUTATHIONE 
• 124-65-2 sodium cacodylate 
• 557-89-1 Dimethylchloroarsine 
• 91919-78-7 cysteinyldimethylthioarsenite 
• 471-35-2 tetramethyldiarsine 
• 75-60-5 Dimethylarsinic acid 

Relevant articles and documents

Toxicity of a trivalent organic arsenic compound, dimethylarsinous glutathione in a rat liver cell line (TRL 1215)

Background and purpose:Although inorganic arsenite (AsIII) is toxic in humans, it has recently emerged as an effective chemotherapeutic agent for acute promyelocytic leukemia (APL). In humans and most animals, As III is enzymatically methylated in the liver to weakly toxic dimethylarsinic acid (DMAsV) that is a major pentavalent methylarsenic metabolite. Recent reports have indicated that trivalent methylarsenicals are produced through methylation of AsIII and participate in arsenic poisoning. Trivalent methylarsenicals may be generated as arsenical-glutathione conjugates, such as dimethylarsinous glutathione (DMAsIIIG), during the methylation process. However, less information is available on the cytotoxicity of DMAsIIIG.Experimental approach:We synthesized and purified DMAsIIIG using high performance TLC (HPTLC) methods and measured its cytotoxicity in rat liver cell line (TRL 1215 cells).Key results:DMAsIIIG was highly cytotoxic in TRL 1215 cells with a LC50 of 160 nM. We also found that DMAsIIIG molecule itself was not transported efficiently into the cells and was not cytotoxic; however it readily became strongly cytotoxic by dissociating into trivalent dimethylarsenicals and glutathione (GSH). The addition of GSH in micromolar physiological concentrations prevented the breakdown of DMAs IIIG, and the DMAsIIIG-induced cytotoxicity. Physiological concentrations of normal human serum (HS), human serum albumin (HSA), and human red blood cells (HRBC) also reduced both the cytotoxicity and cellular arsenic uptake induced by exposure to DMAsIIIG.Conclusions and implications:These findings suggest that the significant cytotoxicity induced by DMAsIIIG may not be seen in healthy humans, even if DMAs IIIG is formed in the body from AsIII.

COMPOUNDS AND METHODS FOR THE TREATMENT OF CANCER

The present invention relates generally to the field of anti-cancer therapy. More particularly, it provides novel crystalline forms of organic arsenic compounds and methods for their use in treating cancers such as leukemia and solid tumors. Specifically, a crystalline form of darinaparsin, wherein the crystalline form has a melting point in the range of about 190-200 deg C.

ORGANOARSENIC COMPOUNDS AND METHODS FOR THE TREATMENT OF CANCER

A method for treating a lymphoma selected from non-Hodgkin's and Hodgkin's lymphoma comprising administering an organoarsenic compound having a structure of the formula (I) wherein X is S or Se and R1 and R2 are independently C1-30alkyl(R3, R3′, R4, R5, W and “n” are as defined in claim 1) in particular where the compound is S-dimethylarsinoglutathione, N-(2-S-dimethylarsinothiopropionyl)glycine, 2-amino-3-(dimethylarsino)thio-3-methylbutanoic acid, S-dimethylarsino-thiosuccinic acid or S-dipropylarsino-1-thioglycerol.