ITPP

• CAT Number: M144244
• CAS Number: 802590-64-3
• Molecular Formula: C6H12O21P6
• Molecular Weight: 605.984
• Purity: ≥95%
• Synonyms: myo-Inositol 1,6; myo-Inositol trispyrophosphate
• Storage: RT
• IUPAC Name: methyl [(1R,4S)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonate
• InChI: InChI=1S/C6H12O21P6/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)
• InChIKey: HEDKSUBRULAYNO-UHFFFAOYSA-N
• SMILES: C12C(C3C(C4C1OP(=O)(OP(=O)(O4)O)O)OP(=O)(OP(=O)(O3)O)O)OP(=O)(OP(=O)(O2)O)O

ITPP (Myo-inositol trispyrophosphate)(CAT: M144244) is an allosteric modifier of hemoglobin, which means it can enhance the release of oxygen from red blood cells. ITPP is a synthetic compound derived from inositol, a naturally occurring sugar alcohol. ITPP has been studied for its potential use in sports performance enhancement and as a treatment for conditions associated with low oxygen levels, such as chronic obstructive pulmonary disease (COPD), altitude sickness, and sickle cell disease. It has also been investigated for its potential use in cancer treatment, as tumors can create a hypoxic (low-oxygen) environment that can promote their growth and spread.

Reference

1. Anticancer Res. 2016 Nov;36(11):5751-5755.
ITPP Treatment of RG2 Glioblastoma in a Rat Model.
Förnvik K(1), Zolfaghari S(2), Salford LG(2), Redebrandt HN(2).
Author information:
(1)The Rausing Laboratory, Division of Neurosurgery, Department of Clinical Sciences Lund, Lund University, Lund, Sweden . (2)The Rausing Laboratory, Division of Neurosurgery, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
BACKGROUND: Inositol trispyrophosphate (ITPP) has been shown to reduce tumour growth in different animal cancer models, as well as of human U87 glioma cells grafted onto chick chorioallantoic membrane (CAM). The aim of this study was to establish whether ITPP crosses the blood-brain barrier and whether it halts the growth of RG2 glioblastoma tumour.
MATERIALS AND METHODS: A model comprising of Fischer 344 rats was chosen and RG2 cells were implanted either intracranially, or subcutaneously on the left hind leg, and the animals were treated with ITPP either intraperitoneally, intravenously or both routes combined. Overall survival was then calculated. RESULTS: No prolonged survival was seen in animals treated with ITPP. The route of ITPP administration did not affect outcome.
CONCLUSION: ITPP had no favourable effect upon survival in our animal model with RG2 glioblastoma tumours in Fischer 344 rats.

2. Drug Test Anal. 2014 Nov-Dec;6(11-12):1102-7. doi: 10.1002/dta.1700. Epub 2014 Jul 28.
Screening and confirmation of myo-inositol trispyrophosphate (ITPP) in human urine by hydrophilic interaction liquid chromatography high resolution / high accuracy mass spectrometry for doping control purposes.
Görgens C(1), Guddat S, Schänzer W, Thevis M.
Author information:
(1)Institute of Biochemistry – Center for Preventive Doping Research, German Sport University Cologne, Am Sportpark Müngersdorf 6, 50933, Cologne, Germany.
Myo-inositol trispyrophosphate (ITPP) is a novel allosteric effector of haemoglobin with high permeation selectivity across the red blood cell plasma membrane. Due to its potential to reduce the oxygen affinity of haemoglobin, ITPP application results in an enhanced oxygen release in hypoxic tissues. Therefore, ITPP is being examined for the treatment of numerous illnesses that involve hypoxia, such as cardiovascular diseases, cancer or Alzheimer's disease. Similar to the prohibited substance Efaproxiral®, ITPP increases maximal exercise capacity in mice, providing high potential to be misused in sports. To keep up with cheating athletes, a fast and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for screening and confirmation of ITPP in human urine for doping control purposes was developed. According to the molecule's distinct hydrophilic properties, extraction from complex biological matrices is challenging and conventional reversed phase liquid chromatography (RPLC) separations are not suitable for its detection. Therefore an approach based on hydrophilic interaction liquid chromatography (HILIC) Orbitrap mass spectrometry was established. The methodology was fully validated for qualitative purposes. Screening and confirmation assay are characterized by satisfactory specificity and robustness, adequate intra-day (screening: 4.9-8.1%; confirmation: 2.0-6.7%) and inter-day precision (screening: 4.6-9.1%; confirmation: 1.8-6.6%), excellent linear correlations (>0.99) with sufficient LLOD in the sub ng/mL range (screening: 15 ng/mL; confirmation: 1 ng/mL). In addition it could be shown that ITPP is stable in human urine under the mandatory storage period and conditions for doping control laboratories. To our knowledge, this is the first validated 'dilute-and-inject' LC-MS/MS method for the reliable detection of ITPP in human urine.

3. Drug Test Anal. 2014 Mar;6(3):268-76. doi: 10.1002/dta.1473. Epub 2013 Jun 4.
Detection of myo-inositol tris pyrophosphate (ITPP) in equine following an administration of ITPP.
Lam G(1), Zhao S, Sandhu J, Yi R, Loganathan D, Morrissey B.
Author information:
(1)Maxxam Analytics Inc., 8577 Commerce Court, Burnaby, BC, V5A 4N5, Canada.
Myo-Inositol tris pyrophosphate (ITPP) is a powerful allosteric modulator of haemoglobin that increases oxygen-releasing capacity of red blood cells. It is capable of crossing the red blood cell membrane unlike its open polyphosphate analog myo-inositol hexakisphosphate (IHP). Systemic administration of ITPP enhanced the exercise capacity in mice. There have been rumours of its abuse in the horse racing industry to enhance the performance of racing horses. In this paper, the detection of ITPP in equine plasma and urine after an administration of ITPP is reported. A Standardbred mare was administered 200 mg of ITPP intravenously. Urine and plasma samples were collected up to 120 h post administration and analyzed for ITPP by liquid chromatography-tandem mass spectrometry. ITPP was detected in post administration plasma samples up to 6 hours. The peak concentration was detected at 5 min post administration. In urine, ITPP was detected up to 24 h post administration. The peak concentration was detected at 1.5 h post administration.