An approved drug, typically consisting of a single active pharmaceutical ingredient, can take 10 – 12 years and cost over a billion dollars to develop. Small molecules and biologics are highly regulated for their pharmacological properties, safety, and efficacy. These results can be used as a starting point for further exploration on the toxicity potential and clinical relevance of these substances. Overall, we highlight four significant bioactivity profiles (measured by p-values) as examples of this prediction. Based on the premise that compounds with similar activity profiles tend to share similar targets or MOA, we clustered the library activity profiles to identify overlap with the NCATS Pharmaceutical Collection to predict the MOAs of the DSNP/TCM substances. Many of the approved drugs have well-annotated mechanisms of action (MOA) while the MOAs for most of the DSNP and TCM samples remain unknown. In addition, we compared the activity profiles of the DSNP/TCM substances with those of an approved drug collection.
This pipeline facilitated the interrogation of Natural Product-Drug Interaction (NaPDI) through prominent metabolizing pathways. We assembled a collection of Dietary Supplements and Natural Products (DSNP) as well as Traditional Chinese Medicinal (TCM) Plant extracts, which were screened against an in vitro panel of assays, including a liver cytochrome p450 enzyme panel, CAR/PXR signaling pathways, and P-gp transporter assays, to assess their activity. Dietary Supplements and Natural Products have minor oversight of their safety and efficacy.
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