Darinaparsin (ZIO-101, SP-02) is a novel and potent mitochondrial-targeted small molecule and an organic arsenic that is being developed for the treatment of various hematologic and solid cancers. Intravenous darinaparsin showed evidence of clinical activity in malignant lymphoma, particularly peripheral T-cell lymphoma (PTCL), in a Phase II study conducted in the U.S. In order to treat PTCL, darinaparsin received Orphan Drug Designation in the U.S. and Europe. Solasia plans to apply for a similar designation in Japan. Inorganic arsenicals (iAs) in vivo produce darinaparsin, a highly toxic metabolic intermediate. When glutathione (GSH) levels are low, darinaparsin appears to produce volatile cytotoxic arsenic compounds, though the precise mechanism of action is unknown. In addition, this substance or its byproducts may initiate cell death by interrupting the G2/M phase of the cell cycle and may exhibit antiangiogenic effects. The arsenic compounds generated from darinaparsin disrupt mitochondrial bioenergetics, producing reactive oxygen species (ROS) and inducing ROS-mediated tumor cell apoptosis.

Physicochemical Properties

Molecular Formula	C12H22ASN3O6S
Molecular Weight	411.30618
Exact Mass	411.045
Elemental Analysis	C, 35.04; H, 5.39; As, 18.22; N, 10.22; O, 23.34; S, 7.80
CAS #	69819-86-9
Related CAS #	69819-86-9
PubChem CID	11683005
Appearance	White to off-white solid powder
LogP	1.229
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	11
Heavy Atom Count	23
Complexity	449
Defined Atom Stereocenter Count	2
SMILES	C[As](SC[C@H](NC(CC[C@H](N)C(O)=O)=O)C(NCC(O)=O)=O)C
InChi Key	JGDXFQORBMPJGR-YUMQZZPRSA-N
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
Chemical Name	(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-dimethylarsanylsulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
Synonyms	Darinaparsin; Zinapar; SP-02; SP 02; SP02; ZIO 101; ZIO101; ZIO-101
HS Tariff Code	2934.99.9001
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)

Biological Activity

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].
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].
References	[1]. 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.
Additional Infomation	(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-(dimethylarsinothio)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid is a peptide. Darinaparsin is a small-molecule organic arsenical with potential antineoplastic activity. Although the exact mechanism of action is unclear, darinaparsin, a highly toxic metabolic intermediate of inorganic arsenicals (iAs) that occurs in vivo, appears to generate volatile cytotoxic arsenic compounds when glutathione (GSH) concentrations are low. The arsenic compounds generated from darinaparsin disrupt mitochondrial bioenergetics, producing reactive oxygen species (ROS) and inducing ROS-mediated tumor cell apoptosis; in addition, this agent or its byproducts may initiate cell death by interrupting the G2/M phase of the cell cycle and may exhibit antiangiogenic effects. Compared to inorganic arsenic compounds such as arsenic trioxide (As2O3), darinaparsin appears to exhibit a wide therapeutic window. Drug Indication Investigated for use/treatment in blood (blood forming organ disorders, unspecified), cancer/tumors (unspecified), solid tumors, multiple myeloma, and liver cancer.

Solubility Data

Solubility (In Vitro)

H2O: ~62.5 mg/mL (~152.0)

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.