View source for Myo-Inositol trispyrophosphate

{{DISPLAYTITLE:''myo''-Inositol trispyrophosphate}}
{{Chembox
| Name = ''myo''-Inositol trispyrophosphate
| ImageFile = ITPP bkchem autocropped.svg
| ImageAlt = Chemical structure of ITPP
| IUPACName =
| OtherNames = {{bulletedlist|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)|Hexahydrobis[1,3,5,2,4]trioxadiphosphepino[6,7-g:6',7'-i][1,3,5,2,4]benzotrioxadiphosphepine-2,4,7,9,12,14-hexol 2,4,7,9,12,14-hexaoxide}}
|Section1={{Chembox Identifiers
| CASNo = 623552-11-4
| PubChem = 10439981
| ChemSpiderID = 8615402
| SMILES = C12C(C3C(C4C1OP(=O)(OP(=O)(O4)O)O)OP(=O)(OP(=O)(O3)O)O)OP(=O)(OP(=O)(O2)O)O
| 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
| StdInChI = 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)
| StdInChIKey = HEDKSUBRULAYNO-UHFFFAOYSA-N
| RTECS =
| MeSHName = C516441
| ChEBI =
| KEGG = }}
|Section2={{Chembox Properties
| C=6 | H=12 | O=21 | P=6
| Appearance =
| Density =
| MeltingPtC =
| BoilingPt =
| Solubility = }}
|Section3={{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt = }}
}}
'''''myo''-Inositol trispyrophosphate''' ('''ITPP''') is an [[inositol phosphate]], a [[pyrophosphate]], a [[drug development|drug candidate]], and a putative [[performance-enhancing substance]], which exerts its biological effects by increasing tissue oxygenation.<ref name=pmid19204295>{{cite journal | pmid = 19204295 | year = 2009 | last1 = Biolo | first1 = A | title = Enhanced exercise capacity in mice with severe heart failure treated with an allosteric effector of hemoglobin, myo-inositol trispyrophosphate. | journal = Proc Natl Acad Sci U S A | volume = 106 | issue = 6 | pages = 1926–1929 | last2 = Greferath | first2 = R | last3 = Siwik | first3 = DA | last4 = Qin | first4 = F | last5 = Valsky | first5 = E | last6 = Fylaktakidou | first6 = KC | last7 = Pothukanuri | first7 = S | last8 = Duarte | first8 = CD | last9 = Schwarz | first9 = RP | last10 = Lehn | first10 = JM | last11 = Nicolau | first11 = C | last12 = Colucci | first12 = WS | doi = 10.1073/pnas.0812381106 | pmc = 2644140 | bibcode = 2009PNAS..106.1926B | doi-access = free }}</ref>
==Chemistry==
ITPP is a [[pyrophosphate]] [[derivative (chemistry)|derivative]] of [[phytic acid]] with the molecular formula C<sub>6</sub>H<sub>12</sub>O<sub>21</sub>P<sub>6</sub>.<ref name=pmid19204295/>
==Biological effects==
ITPP is a [[Cell membrane#Permeability|membrane-permeant]] [[allosteric regulation|allosteric regulator]] of [[hemoglobin]] that mildly reduces its [[Oxygen-hemoglobin dissociation curve|oxygen-binding affinity]], which shifts the oxygen-hemoglobin dissociation curve to the right and thereby increases oxygen release from the blood into tissue.<ref name=pmid19204295/>  [[Phytic acid]], in contrast, is not membrane-permeant due to its [[Hydrophile#Molecules|charge distribution]].<ref name=pmid19204295/>
Rodent studies ''[[in vivo]]'' demonstrated increased tissue oxygenation and [[dose-response relationship|dose-dependent]] increases in endurance during physical exercise, in both healthy mice and transgenic mice expressing a heart failure phenotype.<ref name=pmid19204295/>
The substance is believed to have a high potential for use in [[Doping in sport|athletic doping]], and [[liquid chromatography–mass spectrometry]] tests have been developed to detect ITPP in [[Clinical urine tests#Drugs|urine tests]].<ref name=pmid25070041>{{cite journal | pmid = 25070041 | year = 2014 | last1 = Görgens | first1 = C | title = 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. | journal = Drug Test. Anal. | volume = 6 | issue = 11–12 | pages = 1102–1107 | last2 = Guddat | first2 = S | last3 = Schänzer | first3 = W | last4 = Thevis | first4 = M | doi = 10.1002/dta.1700 | doi-access = free }}</ref>  Its use as a performance-enhancing substance in [[horse racing]] has also been suspected and similar tests have been developed for horses<ref name=pmid23733541>{{cite journal | pmid = 23733541 | year = 2014 | last1 = Lam | first1 = G | title = Detection of myo-inositol tris pyrophosphate (ITPP) in equine following an administration of ITPP. | journal = Drug Test. Anal. | volume = 6 | issue = 3 | pages = 268–276 | last2 = Zhao | first2 = S | last3 = Sandhu | first3 = J | last4 = Yi | first4 = R | last5 = Loganathan | first5 = D | last6 = Morrissey | first6 = B | doi = 10.1002/dta.1473 }}</ref>
ITPP has been studied for potential [[adjuvant]] use in the treatment of [[cancer]] in conjunction with [[chemotherapy]], due to its effects in reducing [[Hypoxia (medical)|tissue hypoxia]].<ref name=pmid28742687>{{cite journal | pmid = 28742687 | year = 2017 | last1 = Limani | first1 = P | title = The Allosteric Hemoglobin Effector ITPP Inhibits Metastatic Colon Cancer in Mice. | journal = Ann. Surg. | volume = 266 | issue = 5 | pages = 746–753 | last2 = Linecker | first2 = M | last3 = Schneider | first3 = MA | last4 = Kron | first4 = P | last5 = Tschuor | first5 = C | last6 = Kachaylo | first6 = E | last7 = Ungethuem | first7 = U | last8 = Nicolau | first8 = C | last9 = Lehn | first9 = JM | last10 = Graf | first10 = R | last11 = Humar | first11 = B | last12 = Clavien | first12 = PA | doi = 10.1097/SLA.0000000000002431 | s2cid = 20565432 | url = https://www.zora.uzh.ch/id/eprint/139098/1/95978.pdf }}</ref>  Human clinical trials were registered in 2014 under the [[List of pharmaceutical compound number prefixes|compound number]] OXY111A.<ref name=pmid27756258>{{cite journal | pmid = 27756258 | year = 2016 | last1 = Limani | first1 = P | title = 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. | journal = BMC Cancer | volume = 16 | issue = 1 | pages = 812 | last2 = Linecker | first2 = M | last3 = Kron | first3 = P | doi = 10.1186/s12885-016-2855-3 | pmc = 5070093 | doi-access = free }}</ref>  The substance has also been examined in the context of other illnesses involving hypoxia, such as [[cardiovascular disease]] and [[dementia]]<ref name=pmid25070041/>
== See also ==
* [[Phytic acid]]
* [[Inositol]]
* [[Inositol phosphate]]
* [[Inositol trisphosphate]]
* [[myo-Inositol|''myo''-Inositol]]
== References ==
{{reflist}}
{{DEFAULTSORT:Inositol trispyrophosphate, myo-}}
[[Category:Phospholipids]]
[[Category:Inositol]]
[[Category:Signal transduction]]