REVIEW GNE-490 is a highly selective pan-PI3K inhibitor that demonstrates selectivity over mTOR. It has good pharmacokinetic (PK) parameters and demonstrates knock down of pathway markers in vivo. Originally obtained via modification of compounds like GDC-0941, GNE-490 which have a significantly reduced potency mTOR while maintaining effective potency for PI3K substrates. IC50 values for PI3K family members are in the subnanomolar to low nanomolar range (-.28 to <20nm) while IC50 values for mTOR and other related tyrosine kinases are greater than 750 nM with most being greater than 1 uM or more, thus GNE-490 makes a good choice for examining PI3K related events separate from those mediated by mTOR.
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