| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg | |||
| 50mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Darinaparsin's mechanism of action involves multiple cellular targets. It accumulates in mitochondria, induces mitochondrial membrane depolarization, and triggers reactive oxygen species (ROS) bursts, thereby activating intrinsic apoptosis pathways. It also inhibits the alternative NF-κB pathway and prevents the recruitment of the transcriptional coregulator Brahma-related gene 1 (BRG1) to the HMOX1 promoter. When glutathione (GSH) levels are low, it appears to produce volatile cytotoxic arsenic compounds.
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| ln Vitro |
Darinaparsin is cytotoxic to prostate cancer cell lines and live prostate cancer cells at low micromolar concentrations, and it has the important property of inhibiting the so-called tumor-initiating cells (TIC) subpopulations[1].
In vitro, Darinaparsin demonstrates potent anticancer activity against a range of cancer cell lines. It induces apoptosis and oxidative stress to a greater extent than arsenic trioxide (As₂O₃), within a c-Jun NH2-terminal kinase-dependent mechanism. It has shown IC₅₀ values of 0.5–3.0 µM against HL-60 cells. It is effective against hematologic malignancies and solid tumors, including those resistant to conventional therapies. |
| ln Vivo |
Darinaparsin reduces the ability of prostate cancer cells to initiate tumors and slows the growth of the castrate-resistant Du145 prostate tumor grown as a xenograft in mice[1].
In vivo, Darinaparsin has demonstrated antitumor activity in preclinical models and is being investigated in clinical trials. It functions as a tumor hypoxic cytotoxin and radiosensitizer, enhancing the effects of radiation therapy. Its ability to induce apoptosis and disrupt mitochondrial function in cancer cells translates to tumor growth inhibition in animal models. It is currently under preclinical and clinical investigation for relapsed/refractory lymphomas and solid tumors. |
| Enzyme Assay |
The in vitro activity of Darinaparsin is assessed using cell viability and apoptosis assays. In a standard protocol, cancer cells are seeded in multi-well plates and treated with increasing concentrations of Darinaparsin for 48-72 hours. Cell viability is measured using an MTT or CellTiter-Glo assay. Apoptosis is quantified by staining cells with Annexin V and propidium iodide, followed by flow cytometry analysis. The IC50 is calculated from the dose-response curve.
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| Cell Assay |
Cellular assays for Darinaparsin involve studying its effects on mitochondrial function and ROS production. Cells are treated with the compound, and mitochondrial membrane potential is measured using a fluorescent dye such as JC-1. ROS levels are detected using a cell-permeable fluorescent probe like DCFH-DA. These assays confirm the compound's mechanism of action, which involves mitochondrial disruption and oxidative stress.
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| Animal Protocol |
The in vivo efficacy of Darinaparsin has been evaluated in xenograft mouse models. In these studies, human tumor cells are implanted subcutaneously into immunodeficient mice. When tumors reach a certain size, the animals are treated with Darinaparsin via intravenous injection. Tumor growth is monitored by caliper measurements, and tumor weights are assessed at the end of the study. The compound's ability to inhibit tumor growth is compared to control groups.
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| ADME/Pharmacokinetics |
Darinaparsin is administered intravenously. It is a small molecule with a molecular weight of 398.31 and a molecular formula of C₆H₁₄AsNO₃S. In clinical trials, it has been given for five consecutive days, repeated every 28 days for up to six months. It is being investigated in phase 1 and phase 2 trials for various hematologic cancers and solid tumors.
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| Toxicity/Toxicokinetics |
The toxicity of Darinaparsin has been evaluated in preclinical and clinical studies. As an organic arsenic compound, its toxicity profile is related to its mechanism of action, which involves mitochondrial disruption and oxidative stress. However, its modified chemical structure is designed to enhance its therapeutic index and reduce toxicity compared to traditional arsenic trioxide therapies. The most common adverse events are expected to be related to its effects on rapidly dividing cells.
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| References | |
| Additional Infomation |
(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-(dimethylarsiothio)-1-oxopropyl-2-yl]amino]-5-oxovaleric acid is a peptide. Dalinapasine is a small-molecule organic arsenic compound with potential antitumor activity. Although its exact mechanism of action is unclear, dalinapasine is a highly toxic metabolic intermediate of inorganic arsenic (iAs) in vivo, and it appears to generate volatile cytotoxic arsenic compounds at low glutathione (GSH) concentrations. The arsenic compounds generated by dalinapasine disrupt mitochondrial bioenergetics, producing reactive oxygen species (ROS) and inducing ROS-mediated tumor cell apoptosis; furthermore, the compound or its byproducts may initiate cell death by interfering with the G2/M phase of the cell cycle and may exhibit anti-angiogenic effects. Compared to inorganic arsenic compounds such as arsenic trioxide (As2O3), dalinapasine appears to have a broader therapeutic window.
Drug Indications Studied for the treatment of hematologic disorders (hematopoietic organ diseases, not specified), cancers/tumors (not specified), solid tumors, multiple myeloma, and liver cancer. Darinaparsin (ZIO-101) is a novel organic arsenical apoptosis inducer. It is being developed for the treatment of various cancers, particularly hematologic malignancies such as peripheral T-cell lymphoma and multiple myeloma. Unlike traditional arsenic trioxide, darinaparsin has a modified chemical structure that enhances its therapeutic index and reduces toxicity. It is currently under preclinical and clinical investigation for relapsed/refractory lymphomas and solid tumors. |
| Molecular Formula |
C12H22ASN3O6S
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|---|---|
| Molecular Weight |
411.30618
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| Exact Mass |
411.045
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| Elemental Analysis |
C, 35.04; H, 5.39; As, 18.22; N, 10.22; O, 23.34; S, 7.80
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| CAS # |
69819-86-9
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| Related CAS # |
69819-86-9
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| PubChem CID |
11683005
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| Appearance |
White to off-white solid powder
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| LogP |
1.229
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
23
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| Complexity |
449
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[As](SC[C@H](NC(CC[C@H](N)C(O)=O)=O)C(NCC(O)=O)=O)C
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| InChi Key |
JGDXFQORBMPJGR-YUMQZZPRSA-N
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| InChi Code |
InChI=1S/C12H22AsN3O6S/c1-13(2)23-6-8(11(20)15-5-10(18)19)16-9(17)4-3-7(14)12(21)22/h7-8H,3-6,14H2,1-2H3,(H,15,20)(H,16,17)(H,18,19)(H,21,22)/t7-,8-/m0/s1
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| Chemical Name |
(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-dimethylarsanylsulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
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| Synonyms |
Darinaparsin; Zinapar; SP-02; SP 02; SP02; ZIO 101; ZIO101; ZIO-101
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O: ~62.5 mg/mL (~152.0)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4313 mL | 12.1563 mL | 24.3126 mL | |
| 5 mM | 0.4863 mL | 2.4313 mL | 4.8625 mL | |
| 10 mM | 0.2431 mL | 1.2156 mL | 2.4313 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01139346 | Completed | Drug: darinaparsin | Advanced Solid Tumors | Alaunos Therapeutics | June 2010 | Phase 1 |
| NCT00591396 | Completed | Drug: ZIO-101 (Darinaparsin) |
Solid Tumors | Alaunos Therapeutics | July 2005 | Phase 1 |
| NCT00303199 | Completed | Drug: ZIO-101 (Darinaparsin) |
Multiple Myeloma | Alaunos Therapeutics | July 2005 | Phase 1 Phase 2 |
| NCT00509782 | Completed | Drug: ZIO-101 | MSolid Tumors | M.D. Anderson Cancer Center | May 2005 | Phase 1 |
| NCT00421213 | Completed | Drug: Darinaparsin | Hematologic Neoplasms Bone Marrow Neoplasms |
Alaunos Therapeutics | December 2006 | Phase 1 |
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