ITPP (Myo-inositol trispyrophosphate)

ITPP (Myo-Inositol Trispyrophosphate)

ITPP is a synthetic allosteric effector of haemoglobin: a myo-inositol core carrying three pyrophosphate bridges, supplied as the hexasodium salt. It was designed as a membrane-permeant analogue of 2,3-bisphosphoglycerate, the endogenous effector that sets the oxygen affinity of haemoglobin inside the red cell. The design problem it solves is delivery. Inositol hexaphosphate is a far more potent effector than 2,3-BPG but cannot cross the erythrocyte membrane, so it is useless outside a cell-free system; the trispyrophosphate is permeant, which is what makes it a usable reagent.

The consequence of that binding is a right shift in the oxygen dissociation curve. Loaded red cells hold oxygen less tightly and release more of it at a given partial pressure, and the reported shift in P50 is substantial rather than marginal. This is the reason ITPP appears across two otherwise unrelated fields: hypoxia biology, where it is used to relieve low tissue oxygen tension without changing blood flow, and oxygen-transport physiology, where it is a tool for decoupling delivery from perfusion.

Additional Properties

Research Applications & Mechanism of Action

The mechanism is allosteric rather than enzymatic. ITPP binds the central cavity of the haemoglobin tetramer at the site 2,3-BPG occupies, stabilising the low-affinity T state. Nothing is consumed and no catalysis occurs; the equilibrium simply moves. That distinction matters when designing controls, because the effect is on the oxygen-carrying vehicle and not on the tissue being studied. One of the clearest results in the literature is exactly that: applied directly to endothelial cells with no red cells present, the compound did nothing.

Primary fields of in vitro and preclinical laboratory investigation include:

• Oxygen Dissociation Measurement: Determining P50 shifts in treated erythrocyte preparations by tonometry or oximetry.

• Hypoxia-Response Signalling: Examining HIF-1alpha stabilisation and downstream hypoxia-inducible gene expression under controlled low-oxygen conditions.

• Angiogenesis Models: Testing whether relieving hypoxia suppresses endothelial tube formation and VEGF expression in culture.

• Radiation Biology: Serving as a chemical means of raising tissue oxygenation in radiosensitivity models, where the oxygen enhancement effect is the variable under study.

• Erythrocyte Membrane Permeability: Comparing loading behaviour against non-permeant polyanions such as inositol hexaphosphate.

Selected Research Literature

Peer-reviewed preclinical literature indexed on PubMed, provided for scientific context only. These are animal and in-vitro studies; nothing here describes or implies a use for this material.

• Kieda C, Greferath R, Crola da Silva C, Fylaktakidou KC, Lehn JM, Nicolau C. Suppression of hypoxia-induced HIF-1alpha and of angiogenesis in endothelial cells by myo-inositol trispyrophosphate-treated erythrocytes. Proc Natl Acad Sci U S A. 2006;103(42):15576-15581. doi:10.1073/pnas.0607109103
• Aprahamian M, Bour G, Akladios CY, et al. Myo-inositol trispyrophosphate treatment leads to HIF-1alpha suppression and eradication of early hepatoma tumors in rats. Chembiochem. 2011;12(5):777-783. doi:10.1002/cbic.201000619
• Grgic I, Tschanz F, Borgeaud N, et al. Tumor oxygenation by myo-inositol trispyrophosphate enhances radiation response. Int J Radiat Oncol Biol Phys. 2021;110(4):1222-1233. doi:10.1016/j.ijrobp.2021.02.012

Assay note. Kieda et al. found no effect when the compound was applied directly to endothelial cells; the effect appeared only when erythrocytes were present to be loaded. A cell-culture design without red cells is therefore testing the wrong thing, and Grgic et al. add a timing constraint: sequence relative to the intervention changed the outcome.

Analytical Documentation

Purity, identity, and composition vary by manufacturing lot. Kimera Chems does not publish a single fixed purity figure for this item; refer to the batch-specific Certificate of Analysis (COA) issued for the lot received, which reflects third-party analytical testing for that lot. Contact us if a COA for your lot is required.

Storage & Handling

Store at controlled room temperature. Keep tightly closed. Liquid formats: do not refrigerate or freeze. Cold storage may cause the solution to cloud or precipitate. If this occurs, return to room temperature and mix until clear.

Storage guidance is a house recommendation. Analytical documentation is per-lot release testing.

Related Research Compounds

• AICAR
• O-304 (ATX-304)
• Roxadustat FG-4592
• HERC (MTB)

Further reading: ITPP (Myo-inositol trispyrophosphate) research overview

Research Use Disclaimer

Research Use Only Disclaimer: This product is labeled and sold "For Research Use Only — NOT FOR HUMAN CONSUMPTION." It is not a drug, dietary supplement, food, cosmetic, or medical device, and it is not approved by the FDA or any other regulator for human or veterinary use. It is supplied to approved account holders as a research chemical for laboratory use and must be handled in accordance with applicable law.