Cytotoxicity of ruxolitinib- and baricitinib-based PROTACs in different ALL cells and hCD34+ cells
| Compounds . | EC50 (nM) in ALL cells and normal cells . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| MHH–CALL-4 . | KOPN49 . | MHH–CALL-2 . | KOPN75 . | NALM-6 . | 697 . | hCD34+ cells . | ||||
| Parental . | CRBN-KD . | Baricitinib (1.5 µM) . | Lenalidomide (30 µM) . | |||||||
| Compound 5 | 1.5 | 21.6 | 1.2 | 4.0 | 8.3 | 5.8 | 53 | 8.6 | 4.2 | |
| Compound 6 | 0.4 | 44.3 | 0.3 | 1.1 | 1.8 | 2.0 | 89.4 | 28.4 | 3.9 | |
| Compound 7 | 0.4 | 3456.2 | 0.4 | >57 | 1.1 | 2.2 | 1.0 | 13.3 | 4.2 | 1.3 |
| Compound 8 | 5.4 | >3000 | 15.9 | >3000 | >3000 | 76.9 | 138.9 | >3000 | >3000 | |
| Ruxolitinib | >7 000 | >7000 | >7000 | >7000 | >7000 | >7000 | >7000 | >7000 | ||
| Baricitinib | 1 482 | >6000 | >6000 | >6000 | >6000 | >6000 | >6000 | >6000 | ||
| CHZ868 | 180 | |||||||||
| Thalidomide | >7 000 | >7000 | >7000 | >7000 | >7000 | >7000 | >7000 | >7000 | ||
| Lenalidomide | 34 480 | |||||||||
| Pomalidomide | >7 000 | >7000 | >7000 | >7000 | >7000 | >7000 | >7000 | >7000 | ||
| Compounds . | EC50 (nM) in ALL cells and normal cells . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| MHH–CALL-4 . | KOPN49 . | MHH–CALL-2 . | KOPN75 . | NALM-6 . | 697 . | hCD34+ cells . | ||||
| Parental . | CRBN-KD . | Baricitinib (1.5 µM) . | Lenalidomide (30 µM) . | |||||||
| Compound 5 | 1.5 | 21.6 | 1.2 | 4.0 | 8.3 | 5.8 | 53 | 8.6 | 4.2 | |
| Compound 6 | 0.4 | 44.3 | 0.3 | 1.1 | 1.8 | 2.0 | 89.4 | 28.4 | 3.9 | |
| Compound 7 | 0.4 | 3456.2 | 0.4 | >57 | 1.1 | 2.2 | 1.0 | 13.3 | 4.2 | 1.3 |
| Compound 8 | 5.4 | >3000 | 15.9 | >3000 | >3000 | 76.9 | 138.9 | >3000 | >3000 | |
| Ruxolitinib | >7 000 | >7000 | >7000 | >7000 | >7000 | >7000 | >7000 | >7000 | ||
| Baricitinib | 1 482 | >6000 | >6000 | >6000 | >6000 | >6000 | >6000 | >6000 | ||
| CHZ868 | 180 | |||||||||
| Thalidomide | >7 000 | >7000 | >7000 | >7000 | >7000 | >7000 | >7000 | >7000 | ||
| Lenalidomide | 34 480 | |||||||||
| Pomalidomide | >7 000 | >7000 | >7000 | >7000 | >7000 | >7000 | >7000 | >7000 | ||
EC50, 50% effective concentration; KD, knockdown.