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Phosphatidylinositol 3-kinase (PI3K) catalyzes the synthesis of the second messengers PtdIns-(3)-P, PtdIns-(3,4)-P2, and PtdIns-(3,4,5)-P3. The PI3K family of enzymes is comprised of 15 members that are divided into three classes according to their structure, substrate specificity, and mode of regulation. In the class I PI3Ks, p110α is the primary PI3K isoform required for insulin signaling in adipocytes and myotubes and is frequently mutated in primary tumors. Small molecule inhibitors of p110α are of interest in cancer treatment research. PIK-75 is an imidazopyridine that selectively inhibits p110α with an IC50 value of 5.8 nM. It inhibits p110γ and p110β considerably less effectively with IC50 values of 0.076 µM and 1.3 µM, respectively. In adipocytes and myotubes, PIK-75 blocks production of PIP2 and/or PIP3, phosphorylation of Akt, and activation of mTORC1.
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