JAK inhibitors for MPNs: preclinical data
Drug . | JAK2V617F IC50, nM . | JAK2-wt IC50, nM . | JAK1 IC50, nM . | JAK3 IC50, nM . | TYK2 IC50, nM . | Other targets with < 100nM IC50 . | Ba/F3 cells JAK2V617F proliferation IC50, nM . | Endogenous PV erythroid colony growth IC50, nM . | Erythroid colony growth (PV patients) IC50, nM . | Erythroid colony growth (healthy controls) IC50, nM . | Mouse models where efficacy was shown . |
---|---|---|---|---|---|---|---|---|---|---|---|
Ruxolitinib44 | NA | 2.8 | 3.3 | 428 | 19 | None reported | 126 | 67 | 223 | 407 | Ba/F3-JAK2V617F |
SAR30250345-47 | 3 | 3 | 105 | 1040 | 405 | FLT3, RET | 300-580 | < 300-600 | 600-1200 | > 1200 | JAK2V617F transplant |
Lestaurtinib48 | NA | < 1 | NA | 3 | NA | FLT3, TRKA VEGFR2, RET | NA | NA | NA | NA | HEL xenografts |
CYT38783 | NA | 18 | 11 | 155 | 17 | PKD3, PKCμ CDK2, ROCK2 JNK1, TBK1 | 1500 | 500-1000 | 2000-4000 | 2000-4000 | JAK2V617F transplant |
SB151841 | 19 | 23 | 1280 | 520 | 50 | FLT3 | 160 | 63 | 260 | 230 | Ba/F3-JAK2V617F SET-2-JAK2V617F |
AZD148049 | NA | < 0.5 | 1.3 | 3.9 | NA | Aurora-A, TRKA FGFR1, FLT4 | NA | NA | NA | NA | NA |
BMS91154353 | NA | 1.1 | 356 | 73 | 66 | None reported | 70 | 75 | 300 | 1500 | NA |
LY278454454 | NA | NA | NA | NA | NA | NA | 68 | NA | NA | NA | Ba/F3-JAK2V617F |
NS-01852 | NA | < 1 | 33 | 39 | 22 | SRC, FYN ABL, FLT3 | 60 | 224 | 529 | 952 | Ba/F3-JAK2V617F JAK2V617F-transgenic |
XL01950,57 | NA | 2 | 134 | 195 | 344 | NA | NA | NA | NA | NA | HEL xenografts |
2* | 23* | 102* | 33* | None reported* | NA | NA | NA | NA | MPL W515 transplant* |
Drug . | JAK2V617F IC50, nM . | JAK2-wt IC50, nM . | JAK1 IC50, nM . | JAK3 IC50, nM . | TYK2 IC50, nM . | Other targets with < 100nM IC50 . | Ba/F3 cells JAK2V617F proliferation IC50, nM . | Endogenous PV erythroid colony growth IC50, nM . | Erythroid colony growth (PV patients) IC50, nM . | Erythroid colony growth (healthy controls) IC50, nM . | Mouse models where efficacy was shown . |
---|---|---|---|---|---|---|---|---|---|---|---|
Ruxolitinib44 | NA | 2.8 | 3.3 | 428 | 19 | None reported | 126 | 67 | 223 | 407 | Ba/F3-JAK2V617F |
SAR30250345-47 | 3 | 3 | 105 | 1040 | 405 | FLT3, RET | 300-580 | < 300-600 | 600-1200 | > 1200 | JAK2V617F transplant |
Lestaurtinib48 | NA | < 1 | NA | 3 | NA | FLT3, TRKA VEGFR2, RET | NA | NA | NA | NA | HEL xenografts |
CYT38783 | NA | 18 | 11 | 155 | 17 | PKD3, PKCμ CDK2, ROCK2 JNK1, TBK1 | 1500 | 500-1000 | 2000-4000 | 2000-4000 | JAK2V617F transplant |
SB151841 | 19 | 23 | 1280 | 520 | 50 | FLT3 | 160 | 63 | 260 | 230 | Ba/F3-JAK2V617F SET-2-JAK2V617F |
AZD148049 | NA | < 0.5 | 1.3 | 3.9 | NA | Aurora-A, TRKA FGFR1, FLT4 | NA | NA | NA | NA | NA |
BMS91154353 | NA | 1.1 | 356 | 73 | 66 | None reported | 70 | 75 | 300 | 1500 | NA |
LY278454454 | NA | NA | NA | NA | NA | NA | 68 | NA | NA | NA | Ba/F3-JAK2V617F |
NS-01852 | NA | < 1 | 33 | 39 | 22 | SRC, FYN ABL, FLT3 | 60 | 224 | 529 | 952 | Ba/F3-JAK2V617F JAK2V617F-transgenic |
XL01950,57 | NA | 2 | 134 | 195 | 344 | NA | NA | NA | NA | NA | HEL xenografts |
2* | 23* | 102* | 33* | None reported* | NA | NA | NA | NA | MPL W515 transplant* |
NA indicates not available.
Tested on the structurally similar compound EXEL-8232.57