From: Cell cycle-dependent activity of the novel dual PI3K-MTORC1/2 inhibitor NVP-BGT226 in acute leukemia
NVP-BEZ235 | IC50 (nM) | NVP-BGT226 | IC50 (nM) | ||||
---|---|---|---|---|---|---|---|
Induction of apoptosis | At 1000 nM (% apopt.) | At 5000 nM (% apopt.) | Induction of apoptosis | At 1000 nM (% apopt.) | At 5000 nM (% apopt.) | ||
Parental (w/ IL3) | Not reached* | 3 | 6 | Parental (w/ IL3) | 1821 | 7 | 99 |
KIT WT | 1396 | 32 | 85 | KIT WT | 463 | 48 | 97 |
KIT D816V | Not reached | 4 | 23 | KIT D816V | 1791 | 7 | 99 |
KIT D816F | 1244 | 40 | 87 | KIT D816F | 258 | 87 | 89 |
KIT D816Y | 1363 | 5 | 73 | KIT D816Y | 118 | 89 | 96 |
FLT3 WT | 8296 | 38 | 40 | FLT3 WT | 345 | 41 | 99 |
FLT3 S451F | 741 | 49 | 70 | FLT3 S451F | 125 | 93 | 99 |
FLT3 ITD | Not reached | 19 | 27 | FLT3 ITD | 1079 | 38 | 98 |
FLT3 K663Q | Not reached | 17 | 16 | FLT3 K663Q | 1111 | 26 | 98 |
FLT3 D835V | 458 | 52 | 86 | FLT3 D835V | 163 | 84 | 98 |
FLT3 D835Y | Not reached | 19 | 28 | FLT3 D835Y | 1073 | 33 | 98 |
FLT3 N841H | Not reached | 19 | 22 | FLT3 N841H | 1206 | 18 | 99 |
BCR/ABL1 | Not reached | 38 | 39 | BCR/ABL1 | 262 | 56 | 97 |
Inhibition of proliferation | At 10 nM (% alive) | At 100 nM (% alive) | Inhibition of proliferation | At 10 nM (% alive) | At 100 nM (% alive) | ||
Parental (w/ IL3) | 2398 | 89 | 98 | Parental (w/IL3) | 828 | 100 | 86 |
KIT WT | 6 | 12 | 11 | KIT WT | 6 | 24 | 13 |
KIT D816V | 8 | 40 | 38 | KIT D816V | 153 | 110 | 47 |
KIT D816Y | 72 | 64 | 62 | KIT D816Y | 65 | 112 | 26 |
FLT3 WT | 7 | 33 | 28 | FLT3 WT | 40 | 66 | 27 |
FLT3 K663Q | 91 | 57 | 51 | FLT3 K663Q | 277 | 79 | 52 |
FLT3 ITD | 7 | 13 | 4 | FLT3 ITD | 3 | 4 | 9 |
FLT3 D835V | 10 | 50 | 51 | FLT3 D835V | 141 | 58 | 47 |
FLT3 D835Y | 5 | 37 | 30 | FLT3 D835Y | 35 | 65 | 33 |
FLT3 N841H | 9 | 43 | 47 | FLT3 N841H | 89 | 110 | 38 |
BCR/ABL1 | 131 | 58 | 50 | BCR/ABL1 | 183 | 73 | 52 |