Darinaparsin (Synonyms: Dimethylarsinic glutathione) |
Katalog-Nr.GC43379
One-Click Copy Product Info
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Darinaparsin (ZIO-101), ein organisches Arsen, ist ein auf die Mitochondrien gerichteter Wirkstoff. Darinaparsin induziert Apoptose in Krebszellen und hat Antikrebswirkungen.
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Cas No.: 69819-86-9
Sample solution is provided at 25 µL, 10mM.
Darinaparsin is a novel organic arsenic compound with IC₅₀ values of 0.5–3.0µM against HL-60, Jurkat, HepG2, and A549 cells[1]. Darinaparsin is currently under preclinical and clinical investigation for relapsed/refractory lymphomas and solid tumors[2]. Darinaparsin accumulates in mitochondria, induces mitochondrial membrane depolarization, and triggers reactive oxygen species (ROS) bursts, thereby activating intrinsic apoptosis pathways[4]. Additionally, Darinaparsin downregulates pro-angiogenic factors such as VEGF and IL-8, inhibiting endothelial tube formation [4].
In vitro, treatment of human multiple myeloma cells (8226/S, KMS11) with 2µM Darinaparsin for 6–24 hours significantly upregulated BH3-only proteins like Noxa and Bim, activating the mitochondrial apoptosis pathway. In arsenic trioxide (ATO)-resistant cell lines (8226/S-ATOR05), Darinaparsin still induced apoptosis in a dose-dependent manner, with higher uptake efficiency than ATO in parental cells[5]. Pre-treatment of prostate (HI-LAPC-4), pancreatic (PANC-1), and other solid tumor cells with 3µmol/L Darinaparsin for 4 hours, followed by γ-irradiation under normoxia or hypoxia, significantly enhanced radiosensitivity and induced apoptosis in tumor cells, without sensitizing normal bone marrow and protecting intestinal crypt cells from radiation damage[6].
In vivo, Darinaparsin (100mg/kg) administered via intraperitoneal injection every other day for 10 days in nude mice bearing Du145 or PC3 xenografts significantly inhibited tumor growth without causing weight loss or other toxic effects[7]. Combined treatment with Darinaparsin (50mg/kg) and BMN673 (330mg/kg) via intraperitoneal injection every other day for 14 days in nude mice with DMS273 small-cell lung cancer xenografts also significantly inhibited tumor growth without causing weight loss or other toxic effects[8].
References:
[1] Mann KK, Wallner B, Lossos IS, et al. Darinaparsin: a novel organic arsenical with promising anticancer activity. Expert Opin Investig Drugs. 2009 Nov;18(11):1727-34.
[2] Frampton JE. Darinaparsin: First Approval. Drugs. 2022 Nov;82(16):1603-1609.
[3] Yuan B, Kikuchi H, Li J, et al. Cytotoxic Effects of Darinaparsin, a Novel Organic Arsenical, against Human Leukemia Cells. Int J Mol Sci. 2023 Jan 23;24(3):2282.
[4] Nielsen TH, Johnson N, Garnier N, et al. Monitoring Response and Resistance to the Novel Arsenical Darinaparsin in an AML Patient. Front Pharmacol. 2013 Feb 12;4:9.
[5] Matulis SM, Morales AA, Yehiayan L, et al. Darinaparsin induces a unique cellular response and is active in an arsenic trioxide-resistant myeloma cell line. Mol Cancer Ther. 2009 May;8(5):1197-206.
[6] Tian J, Zhao H, Nolley R, et al. Darinaparsin: solid tumor hypoxic cytotoxin and radiosensitizer. Clin Cancer Res. 2012 Jun 15;18(12):3366-76.
[7] Bansal N, Farley NJ, Wu L, et al. Darinaparsin inhibits prostate tumor-initiating cells and Du145 xenografts and is an inhibitor of hedgehog signaling. Mol Cancer Ther. 2015 Jan;14(1):23-30.
[8] Cao GZ, Ma LY, Zhang ZH, et al. Darinaparsin (ZIO-101) enhances the sensitivity of small-cell lung cancer to PARP inhibitors. Acta Pharmacol Sin. 2023 Apr;44(4):841-852.
| Cell experiment [1]: | |
Cell lines | Human prostate cancer cells (HI-LAPC-4, PC-3, PANC-1, HeLa, SNB-75) |
Preparation Method | Cells were seeded in 6-well plates or 96-well plates, grown to 70–80% confluence, and incubated overnight in hypoxia chambers (0.5% O₂) before treatment. Cells were divided into four groups: control (normoxia), Darinaparsin alone: 3μmol/L Darinaparsin for 4h under normoxia or hypoxia, radiation alone, and Darinaparsin (3μmol/L Darinaparsin for 4h under normoxia or hypoxia) + radiation. |
Reaction Conditions | 3μmol/L; 4h |
Applications | Darinaparsin significantly decreased tumor-cell viability and clonogenic survival under both normoxia and hypoxia, induced G₂/M arrest and apoptosis. |
| Animal experiment [2]: | |
Animal models | Nude rats bearing Du145 xenografts |
Preparation Method | Once tumors reached ~100mm³, rats were randomized and treated with Darinaparsin (100mg/kg; i.p. every other day for 10 days) or vehicle (saline). Tumor volume and body weight were monitored thrice weekly; tumors and blood were harvested on day 45 for histology and pharmacokinetic analyses. |
Dosage form | 100mg/kg; i.p. |
Applications | Darinaparsin significantly inhibited tumor-initiating-cell–driven xenograft growth, reduced tumor volume by >50 % versus controls, and showed no systemic toxicity (no weight loss or organ damage). |
References: | |
| Cas No. | 69819-86-9 | SDF | |
| Überlieferungen | Dimethylarsinic glutathione | ||
| Chemical Name | L-γ-glutamyl-S-(dimethylarsino)-L-cysteinyl-glycine | ||
| Canonical SMILES | OC(CNC([C@H](CS[As](C)C)NC(CC[C@H](N)C(O)=O)=O)=O)=O | ||
| Formula | C12H22AsN3O6S | M.Wt | 411.3 |
| Löslichkeit | 0.1mg/mL in ethanol and DMF, 10mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4313 mL | 12.1566 mL | 24.3132 mL |
| 5 mM | 486.3 μL | 2.4313 mL | 4.8626 mL |
| 10 mM | 243.1 μL | 1.2157 mL | 2.4313 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >95.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 7 reference(s) in Google Scholar.)