Uses
INK1117 is an inhibitor of phosphoinositide 3-kinase α (PI3Kα) that is selective for p110α in vitro (IC50 = 15 nM for PI3Kα vs. >1 μM for other isoforms, as well as for mTOR) and in cells when used at 1 μM. It blocks signaling to Akt and inhibits growth of cancer cells harboring wild-type or mutated p110α. INK1117 does not interfere with B cell proliferation or NK cell maturation and survival.[Cayman Chemical]
Biological Activity
ink1117 is a novel, potent and selective inhibitor of pi3kα with potential antineoplastic activity, which may induce tumor cell apoptosis and growth inhibition in pi3kα-expressing tumor cells. ink1117 dampens signaling to akt and suppresses the growth of cancer cells harboring wild-type or mutated p110α. pi3ks, a family of eight lipid kinase enzymes, produce 3-phosphorylated phosphoinositides in cellular membranes and are promising targets for therapeutic development in cancer.
in vitro
ink1117 blocked class i pi3k enzymes (p110α, p110β, p110γ or p110δ) in the low to mid-nanomolar range in human natural killer (nk) cell lines. ink1117 selectively inhibited pi3k signaling in cellular assays when used at 0.1-1 μm. ink1117 selectively dampened p110 α when used at 1 μm. ink1117 did not inhibit production of ifn-γ protein in cells with anti-nkg2d, indicating that ink1117 did not decrease ifn-γ mrna [1].
in vivo
female c57bl/6 mice were orally given ink1117 at a dose of 60 mg/kg using a sterile disposable 20g-1.5” feeding needle. after 8 days, ink1117 had negligible effects on nk cell maturation or survival. however, ink1117 did not show significantly decrease in the percentage of b cells and did not alter the percentages of t cells or the fractions of cd4 and cd8 t cells, the percentages of nk cells in bone marrow and spleen [1].
IC 50
15nm: inhibits phosphoinositide 3-kinase α (pi3kα) in vitro.
References
[1]. yea, s., so, l., mallya, s., lee, j., rajasekaran, k., malarkannan, s., & fruman, d. effects of novel isoform-selective phosphoinositide 3-kinase inhibitors on natural killer cell function. plos one. 2014; 9(6): e99486.
