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Pharmacology-based Structure-Activity Relationships for Medicinal Chemists

This course describes the conversion of ‘descriptive’ (what we see) data in test systems to ‘predictive’ scales that are system independent and can be used to predict therapeutic activity.

Online Live
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About the Course

Because drugs interact with ongoing physiology in the body, activity can be difficult to predict in therapeutic situations from single estimates of activity in test systems. The main (50%) reason for new drug candidate failure is lack of efficacy. The premise of this course is that pharmacology can now be used to yield more detailed and accurate profiles of drug efficacy that can be used to link activity in the clinic and also provide a better roadmap for follow-up candidates should molecules fail in the clinic.

  • Four main predictive drug properties: affinity, efficacies, allosteric vs orthosteric target engagement, offset rate to predict target coverage in vivo
  • Target activity: enzymes, receptors (agonism, antagonism), protein-protein interactions (allosteric effects), allosteric modulators as drugs
  • Prediction of drug activity under varying physiological conditions in vivo
  • Measurement of target-ligand kinetics to predict in vivo target coverage

What You Will Learn

  • The pharmacological tests that can yield system-independent universal constant of drug activity
  • How a homogeneous set of drug parameters obtained from fitting data to mathematical models can be used to succinctly characterize complex behaviors (namely with allosteric modulators)
  • See examples of SAR threads for receptor agonists, antagonists, allosteric modulators, enzyme inhibitors and how pharmacological parameters can clearly put order in otherwise seemingly chaotic effects

Who Should Attend

Medicinal and synthetic organic chemists, biologists involved in drug development, any scientist involved in process of drug discovery, production and approval.

Course Outline

  • Course Syllabus

    Lecture 1: The four (4) critical parameters needed to describe all drug action: Affinity, efficacies, Allosteric vs Orthosteric interaction, kinetics target offset.

    Lecture 2: Receptors: Cell response activation (agonists), concept of efficacy, predicting agonism in all tissues, biased signaling

    Lecture 3: Receptors: Antagonists: measurement of equilibrium dissociation constants for antagonist-receptor interaction, inverse agonism

    Lecture 4: Allosterism and alteration of large Protein-protein interactions: quantification of cooperativity for affinity (a effect) and efficacy (b effect)

    Lecture 5: Kinetics: measurement of real time kinetics and prediction of target coverage in vivo

    Lecture 6: Enzyme inhibition: Measurement of competitive, non-competitive, uncompetitive and mixed enzyme inhibition; differentiation of mechanism

Dates, Locations, and Prices

Five for four! Register five people for one course, one person for five courses, or any combination in between and your fifth registration is free. The free registration will be the course of the lowest price. Please note: This discount cannot be combined with any other discount offered. 

Each person attending must register individually for this course.

Course fee includes electronic access to the course materials and session recordings. 

About the Instructor(s)

Terry Kenakin

Professor, University of North Carolina School of Medicine

Dr. Terry Kenakin is Professor of Pharmacology at the University of North Carolina School of Medicine. He is the author of 11 books on Pharmacology.

Online Live
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