ITPP
ITPP. A small polyanion — myo-inositol bridged by three cyclic pyrophosphates — that enters red cells through the band 3 anion transporter and binds haemoglobin as an…
A small polyanion — myo-inositol bridged by three cyclic pyrophosphates — that enters red cells through the band 3 anion transporter and binds haemoglobin as an allosteric effector, LOWERING its oxygen affinity and shifting the dissociation curve to higher oxygen partial pressures. The intent is the opposite of most oncology drugs: not to kill tissue but to re-oxygenate it, normalising tumour vasculature so that subsequent chemotherapy works better, and in the endurance-doping market to increase oxygen offloading to muscle. Not a peptide despite the company it keeps on supplement lists.
PubChem CID 10439981 (C6H12O21P6), CAS 802590-64-3. Schneider 2021 (PMID:34155211), an open-label 3+3 dose escalation in 28 patients with hepatopancreatobiliary malignancy and colorectal liver metastases: "nine 8h-infusions of ITPP over three weeks across eight dose levels (1'866-14'500 mg/m2/dose)" and "The maximum tolerated dose is 12,390 mg/m2". DOSES ARE BSA-CONVERTED AND THAT IS A WORKAROUND, NOT A MEASUREMENT: DoseUnit has no per-square-metre member and the solver never scales a dose by body size, so the stored figures are the published mg/m2 multiplied by a conventional 1.73 m2 — min 1866 -> 3.23 g, max 14500 -> 25.09 g, typical at the MTD 12390 -> 21.43 g. This is the same schema gap as the eleven per-kilogram records in AUTHORING_GAPS, one dimension over. THE ROUTE IS AN 8-HOUR INFUSION, which is a zero-order input the record cannot express either, since zo_dur_hr needs a curve to attach to and this record has none. ANIMAL DATA, LABELLED AND NOT STORED: PMID:23733541 is a doping-control study in a single Standardbred mare given 200 mg IV, reporting that "ITPP was detected in post administration plasma samples up to 6 hours. The peak concentration was detected at 5 min post administration" with urine detectable to 24 h — detection windows and a Tmax, no half-life, n of one, and a species the schema would need source_species for if any of it were storable. In-vitro constants exist and are not PK: maximum intracellular concentration 5.5e-3 M and a dissociation constant of 1.72e-5 M for binding to RBC ghosts (PMID:21086482). Mechanism references PMID:15745806 (oxy-haemoglobin dissociation curves "significantly shifted towards higher values of oxygen partial pressures") and PMID:21086482 (band 3 as the entry route, shown by DIDS and NAP-taurine inhibition). The protocol paper is PMID:27756258.
Sources: PMID:34155211, PMID:15745806, PMID:21086482, PMID:23733541, PMID:27756258