Table 3 Activity of A-1574083 (ABBV-4083) in preclinical safety assays.

AssayResult
Chloride channel (GABA-gated)
(antagonist radioligand)
Ki 7.5 μM
NK1 (human) (agonist radioligand)Ki 0.1 μM
NK1(human) (antagonist effect)KB 0.46 μM
Motilin (human) (agonist
radioligand)
IC50 > 100 μM
ERG (human) (QPatch, human
embryonic kidney–293 cells)
IC50 > 28 μM
MiniAmes test (Salmonella TA98/
TA100)
Negative
In vitro micronucleus test (V79
hamster)
Negative
Anesthetized dog cardiovascular
effects (intravenous infusion)
Minimal effects* at 12.4 μg/ml
28-day toxicology study in
Sprague-Dawley rats
NOAEL: 300 mg/kg per day
Plasma AUCss: 7.4 μg·hour/ml
28-day toxicology study in beagle
dogs
NOAEL: 15 mg/kg per day
Plasma AUCss: 3.0 μg·hour/ml

*Monitored characteristics: mean arterial pressure, heart rate, systemic vascular resistance, cardiac output, cardiac contractility, QT interval corrected using Van de Water formula, and interval from P to R on electrocardiogram.