pit-1

PIT-1 is a selective PIP3 antagonist that inhibits cancer cell survival and induces apoptosis by inhibiting PIP3-dependent PI3K/Akt signalling and the PH structural domain of Akt.

PtdIns-(3,4,5)-P3 (PIP3) serves as an anchor for the binding of signal transduction proteins bearing pleckstrin homology (PH) domains such as phosphatidylinositol 3-kinase (PI3K) or PTEN. Protein binding to PIP3 is important for cytoskeletal rearrangement and membrane trafficking and initiates an intricate signaling cascade that has been implicated in cancer. 3,5-dimethyl PIT-1 is a dimethyl analog of PIT-1, the selective inhibitor of PIP3/Akt PH domain binding, that is designed for more favorable solubility in vivo. 3,5-dimethyl PIT-1 inhibits PI3K/Akt signaling (IC50 = 27 μM), suppressing PI3K-PDK1-Akt-dependent phosphorylation, which has been shown to reduce cell viability and induce apoptosis in PTEN-deficient U87MG glioblastoma cells (IC50 = 36 μM). 4T1 breast cancer growth is significantly attenuated in BALB/c mice with a dose of 1 mg/kg of 3,5-dimethyl PIT-1 per day.

DB293 is an inhibitor of PIT-1 and BRN-3 transcription factors. DB293 binds as head-to-tail stacked dimers in the minor groove of 5'-ATGA sequence, thereby leading to an increase in the size of minor groove.

1-Methyl-2-undecyl-4(1H)-quinolone, along with dihydroevocarpine and evodiamine, should serve as chemical markers for the quality control of Evodia rutaecarpa (Juss.) Benth. This compound selectively inhibits type B MAO (MAO-B) activity with an IC(50) value of 15.3 microM using the substrate kynuramine, while not inhibiting type A MAO (MAO-A) activity. It can mitigate high phosphate-induced calcification in human aortic valve interstitial cells (HAVICs) by inhibiting phosphate cotransporter (PiT-1) gene expression and exhibits moderate antiangiogenic activity against human tumor cells.