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myo-Inositol trispyrophosphate

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myo-Inositol trispyrophosphate
Chemical structure of ITPP
Names
Other names
  • ITPP
  • myo-Inositol cyclic 1,2:3,4:5,6-tris(dihydrogen pyrophosphate)
  • myo-Inositol cyclic 1,2:3,4:5,6-tris(P,P'-dihydrogen diphosphate)
  • Hexahydrobistrioxadiphosphepinobenzotrioxadiphosphepine-2,4,7,9,12,14-hexol 2,4,7,9,12,14-hexaoxide
Identifiers
CAS Number
3D model (JSmol)
ChemSpider
MeSH C516441
PubChem CID
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)Key: HEDKSUBRULAYNO-UHFFFAOYSA-N
  • 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)Key: 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
Properties
Chemical formula C6H12O21P6
Molar mass 605.984 g·mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references
Chemical compound

myo-Inositol trispyrophosphate (ITPP) is an inositol phosphate, a pyrophosphate, a drug candidate, and a putative performance-enhancing substance, which exerts its biological effects by increasing tissue oxygenation.

Chemistry

ITPP is a pyrophosphate derivative of phytic acid with the molecular formula C6H12O21P6.

Biological effects

ITPP is a membrane-permeant allosteric regulator of hemoglobin that mildly reduces its oxygen-binding affinity, which shifts the oxygen-hemoglobin dissociation curve to the right and thereby increases oxygen release from the blood into tissue. Phytic acid, in contrast, is not membrane-permeant due to its charge distribution.

Rodent studies in vivo demonstrated increased tissue oxygenation and dose-dependent increases in endurance during physical exercise, in both healthy mice and transgenic mice expressing a heart failure phenotype.

The substance is believed to have a high potential for use in athletic doping, and liquid chromatography–mass spectrometry tests have been developed to detect ITPP in urine tests. Its use as a performance-enhancing substance in horse racing has also been suspected and similar tests have been developed for horses

ITPP has been studied for potential adjuvant use in the treatment of cancer in conjunction with chemotherapy, due to its effects in reducing tissue hypoxia. Human clinical trials were registered in 2014 under the compound number OXY111A. The substance has also been examined in the context of other illnesses involving hypoxia, such as cardiovascular disease and dementia

See also

References

  1. ^ Biolo, A; Greferath, R; Siwik, DA; Qin, F; Valsky, E; Fylaktakidou, KC; Pothukanuri, S; Duarte, CD; Schwarz, RP; Lehn, JM; Nicolau, C; Colucci, WS (2009). "Enhanced exercise capacity in mice with severe heart failure treated with an allosteric effector of hemoglobin, myo-inositol trispyrophosphate". Proc Natl Acad Sci U S A. 106 (6): 1926–1929. Bibcode:2009PNAS..106.1926B. doi:10.1073/pnas.0812381106. PMC 2644140. PMID 19204295.
  2. ^ Görgens, C; Guddat, S; Schänzer, W; Thevis, M (2014). "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". Drug Test. Anal. 6 (11–12): 1102–1107. doi:10.1002/dta.1700. PMID 25070041.
  3. Lam, G; Zhao, S; Sandhu, J; Yi, R; Loganathan, D; Morrissey, B (2014). "Detection of myo-inositol tris pyrophosphate (ITPP) in equine following an administration of ITPP". Drug Test. Anal. 6 (3): 268–276. doi:10.1002/dta.1473. PMID 23733541.
  4. Limani, P; Linecker, M; Schneider, MA; Kron, P; Tschuor, C; Kachaylo, E; Ungethuem, U; Nicolau, C; Lehn, JM; Graf, R; Humar, B; Clavien, PA (2017). "The Allosteric Hemoglobin Effector ITPP Inhibits Metastatic Colon Cancer in Mice" (PDF). Ann. Surg. 266 (5): 746–753. doi:10.1097/SLA.0000000000002431. PMID 28742687. S2CID 20565432.
  5. Limani, P; Linecker, M; Kron, P (2016). "Development of OXY111A, a novel hypoxia-modifier as a potential antitumor agent in patients with hepato-pancreato-biliary neoplasms - Protocol of a first Ib/IIa clinical trial". BMC Cancer. 16 (1): 812. doi:10.1186/s12885-016-2855-3. PMC 5070093. PMID 27756258.
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