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NVP-DKY709 is a selective molecular gel degrader of IKZF2 (IKAROS Family Zinc Finger 2). DKY709 (16-20 hours) treatment of human Jurkat T lymphocytes resulted in a dose-dependent, selective degradation of IKZF2 (Dmax=69%, DC50=11 nM), with no effect on IKZF1 levels. DKY709 also degrades IKZF4 and SALL4. DKY709 degraded IKZF2 in human, non-human primate and rabbit cells, but not in other tested species such as rats, mice, pigs, and dogs. Treatment of phytohemagglutinin (PHA)-stimulated Jurkat T cells with DKY709 resulted in a dose-dependent increase in IL-2 concentrations in the supernatant. DKY709 exhibited good pharmacokinetic properties in mice and monkeys, with rapid absorption and good bioavailability. MDA-MB-231 (breast cancer) xenografts were implanted in humanized (hematopoietic stem cell-derived) mice and DKY709 was administered at a dose of 100 mg/kg once daily. IKZF2 was strongly degraded in both tumor cells and peripheral blood Treg cells.
| Molecular Weight | 417.5 |
| Formula | C25H27N3O3 |
| CAS Number | 2291360-73-9 |
| Solubility (25°C) | DMSO ≥ 10 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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