Assessing the Structural and Pharmacological Similarity of Newly Identified Drugs of Abuse to Controlled Substances Using Public Health Assessment via Structural Evaluation

Clin Pharmacol Ther. 2019 Jul;106(1):116-122. doi: 10.1002/cpt.1418. Epub 2019 Apr 8.


The US Food and Drug Administration's Center for Drug Evaluation and Research (CDER) developed an investigational Public Health Assessment via Structural Evaluation (PHASE) methodology to provide a structure-based evaluation of a newly identified opioid's risk to public safety. PHASE utilizes molecular structure to predict biological function. First, a similarity metric quantifies the structural similarity of a new drug relative to drugs currently controlled in the Controlled Substances Act (CSA). Next, software predictions provide the primary and secondary biological targets of the new drug. Finally, molecular docking estimates the binding affinity at the identified biological targets. The multicomponent computational approach coupled with expert review provides a rapid, systematic evaluation of a new drug in the absence of in vitro or in vivo data. The information provided by PHASE has the potential to inform law enforcement agencies with vital information regarding newly emerging illicit opioids.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics, Opioid / chemistry*
  • Computer Simulation
  • Controlled Substances / chemistry*
  • Drug Design
  • Drug and Narcotic Control / organization & administration*
  • Fentanyl / chemistry
  • Humans
  • Molecular Docking Simulation / methods*
  • Public Health
  • Structure-Activity Relationship
  • United States
  • United States Food and Drug Administration / organization & administration*


  • Analgesics, Opioid
  • Controlled Substances
  • Fentanyl