Weak inhibitor of CYP2D6 (IC50 18 µM) and no significant inhibition of CYP1A2, 2C9, 2C19, or 3A4 at therapeutic exposures (<2 µM).
Normal human CD34+ hematopoietic stem cells and peripheral blood mononuclear cells (PBMCs) tolerate 1 µM EZD-349 for 24 hours with <15% apoptosis, whereas primary CLL or AML blasts show >70% apoptosis at 100 nM. This differential sensitivity is attributed to oncogene addiction: cancer cells rely heavily on MCL-1/MYC for survival, while normal cells use redundant BCL-2/BCL-XL networks. ezd-349
This paper is a composite of available public information as of late 2023. For ongoing clinical trial data, consult clinicaltrials.gov or Debiopharm’s official pipeline. Weak inhibitor of CYP2D6 (IC50 18 µM) and
| Parameter | Mouse (IV, 1 mg/kg) | Dog (PO, 5 mg/kg) | Human predicted | |-----------|---------------------|-------------------|------------------| | Clearance (Cl) | 22 mL/min/kg | 8 mL/min/kg | ~9 mL/min/kg | | Volume of distribution (Vdss) | 2.8 L/kg | 1.9 L/kg | ~2.2 L/kg | | Half-life (t½) | 2.1 h | 4.7 h | 6–8 h | | Oral bioavailability (F%) | 58% | 72% | ~65% | | Plasma protein binding | 78% (mouse), 84% (human) | | | | Brain penetration (Kp,uu) | 0.12 (low CNS exposure) | | | This paper is a composite of available public