Myo-Inositol trispyrophosphate (ITPP) hexasodium is a hemoglobin (haemoglobin) modulator and an allosteric effector that reduces the oxygen-binding affinity of hemoglobin and promotes oxygen release from red blood cells. myo-Inositol trispyrophosphatehexasodium reverses hypoxia, controls tumor growth and improves chemotherapy response.

Physicochemical Properties

Molecular Formula	C6H6NA6O21P6
Molecular Weight	737.88
Exact Mass	737.721
CAS #	23103-35-7
PubChem CID	10439980
Appearance	White to off-white solid powder
LogP	2.633
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	21
Rotatable Bond Count	0
Heavy Atom Count	39
Complexity	857
Defined Atom Stereocenter Count	0
SMILES	[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].O=P1(OP(=O)([O-])OC2C(C3OP(=O)([O-])OP(=O)([O-])OC3C3OP(=O)([O-])OP(=O)([O-])OC32)O1)[O-]
InChi Key	DTOYSAZRROROSE-UHFFFAOYSA-H
InChi Code	InChI=1S/C6H12O21P6.6Na/c7-28(8)19-1-2(20-29(9,10)25-28)4-6(24-33(17,18)27-32(15,16)23-4)5-3(1)21-30(11,12)26-31(13,14)22-5;;;;;;/h1-6H,(H,7,8)(H,9,10)(H,11,12)(H,13,14)(H,15,16)(H,17,18);;;;;;/q;6*+1/p-6
Chemical Name	hexasodium;4,6,11,13,18,20-hexaoxido-3,5,7,10,12,14,17,19,21-nonaoxa-4λ5,6λ5,11λ5,13λ5,18λ5,20λ5-hexaphosphatetracyclo[14.5.0.02,8.09,15]henicosane 4,6,11,13,18,20-hexaoxide
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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
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	All six of the cell lines (FSaII, SiHa, MDA-MB-231, NT2, 9L-glioma, and rhabdomyosarcoma) exhibit significant inhibition of OCR when exposed to myo-Inositol trispyrophosphate hexasodium (10 mmol/L; 2 hours) [2].
ln Vivo	The substantial effect of myo-Inositol trispyrophosphate hexasodium (2 g/kg weekly; IP; 7 weeks) on life prolonging persists[1]. Immunocompetent male Lewis rats weighing 120-150 g with DSL-6A/C1 cells do not develop metastases on pancreatic carcinomas when myo-Inositol trispyrophosphate hexasodium (1.5 g/kg weekly; IV; for 8 weeks) is administered. Tumor pO2 pressure is restored by myo-Inositol trispyrophosphate hexasodium, which also lowers proangiogenic and hypoxia-inducible factors[1]. Myo-Inositol trispyrophosphate hexasodium (2 g/kg; once daily for 2 days) in four mouse tumor models (mouse fibrosarcoma FSaII implanted in C3H mice, mouse mammary tumor NT2 in FVb/Nrj mice, and human breast cancer MDA-MB-231) exhibits the highest level of enhanced tumor oxygenation at 2 hours.
Animal Protocol	Animal/Disease Models: Nude mice (20 g) with MiaPaCa-2 or DSL-6A/C1 cells[1] Doses: 2 g/kg (weekly) Route of Administration: IP; weekly; 7weeks Experimental Results: Sustained its significant effect on life prolongation.
References	[1]. Zahary Raykov, et al. Myo-inositol trispyrophosphate-mediated hypoxia reversion controls pancreatic cancer in rodents and enhances gemcitabine efficacy. Int J Cancer. 2014 Jun 1;134(11):2572-82. [2]. Ly-Binh-An Tran, et al. Impact of myo-inositol trispyrophosphate (ITPP) on tumour oxygenation and response to irradiation in rodent tumour models. J Cell Mol Med. 2019 Mar;23(3):1908-1916. [3]. Marta Oknińska, et al. Treatment of hypoxia-dependent cardiovascular diseases by myo-inositol trispyrophosphate (ITPP)-enhancement of oxygen delivery by red blood cells. J Cell Mol Med. 2020 Feb;24(3):2272-2283.

Solubility Data

Solubility (In Vitro)

H2O: 25 mg/mL (33.88 mM)

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	1.3552 mL	6.7762 mL	13.5523 mL
	5 mM	0.2710 mL	1.3552 mL	2.7105 mL
	10 mM	0.1355 mL	0.6776 mL	1.3552 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.