TABLE 1

Representative compounds identified as heterotropic activators of CYP activity during single-point screening of the SPECTRUM library in HLM

DrugClassificationCYP3A4/5CYP2C9CYP1A2CYP2D6
FlutamideAntiandrogen98
RosiglitazoneAntidiabetic377131
Metformin hydrochlorideAntidiabetic63233263
Coenzyme B12Vitamin56
Pyrvinium pamoateAnthelmintic54
Diclofenac sodiumAnti-inflammatory54
Avocatin BAntibacterial, antifungal52
NilutamideAntiandrogen49
DeracoxibAnti-inflammatory, antiarthritic, cyclooxygenase 2 inhibitor48
RibavirinAntiviral414546
TolbutamideAntidiabetic4522
Tranylcypromine sulfateAntidepressant, monoamine oxidase inhibitor43
Diethylcarbamazine citrateAnthelmintic43
Moxifloxacin hydrochlorideAntibacterial244141
Tacrine hydrochlorideAnticholinesterase, cognitive adjuvant, K channel blocker40
CelecoxibAntiarthritic, cyclooxygenase 2 inhibitor3928
Propantheline bromideAnticholinergic38
Orphenadrine citrateMuscle relaxant (skeletal), antihistaminic382845
SulfanitranAntibacterial37
CanrenoneAldosterone antagonist, antifibrogenic3733
  • Percentage of activation over baseline. The screening concentration for each compound was 10 μM. Values are expressed as the percentage of activity remaining over the baseline and are the average of two replicates. Positive hits were required to have duplicate data points ≥20% increase over baseline. Activity is calculated based on the metabolism of CYP-specific probe substrates to their respective metabolites. The compounds included in the table are representative of the diversity of the therapeutic areas and drug classes that exhibited heterotropic activation of CYP activity. Inhibition of enzymatic activity or no observed effect is designated with a dashed line.