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Related Concept Videos

Drug Discovery: Overview01:26

Drug Discovery: Overview

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Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
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Body:Bioavailability is a critical pharmacological concept that measures the extent and rate at which an active drug ingredient or therapeutic moiety enters the systemic circulation, remaining unchanged. It's a pivotal factor in determining a drug's efficacy and safety.The Biopharmaceutics Classification System (BCS) plays an essential role in drug development by categorizing drugs into four classes based on their solubility and permeability. This classification aids in understanding drug...
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Pharmacokinetic–Pharmacodynamic Relationship: Problems01:24

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The empirical approach to drug therapy optimization relies on correlating pharmacological response with administered dosage. Such an approach can be costly, time-consuming, and often yields poor correlation due to variables like formulation factors and drug elimination characteristics. A more precise approach correlates response with plasma drug concentration or the amount of drug in the body, rather than dosage. This is achieved through pharmacokinetic-pharmacodynamic (PK/PD) modeling, which...
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Biophysics: for HTS hit validation, chemical lead optimization, and beyond.

Christine C Genick1,2, S Kirk Wright2,3

  • 1a Novartis Pharma AG, Novartis Institutes for BioMedical Research, Chemical Biology and Therapeutics , Protein Sciences , Basel , Switzerland.

Expert Opinion on Drug Discovery
|June 30, 2017
PubMed
Summary
This summary is machine-generated.

Biophysics is revolutionizing drug discovery by enabling early target characterization and hit identification. This approach enhances the discovery of novel chemical leads with unique mechanisms of action.

Keywords:
Biophysicsallostericcellular thermal shift assayschemical lead optimizationcovalent modificationhit validationscreeningsurface plasmon resonancethermal shift assays

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Area of Science:

  • Drug Discovery
  • Biophysics
  • Medicinal Chemistry

Background:

  • Traditional drug discovery faces challenges from complex targets and disease mechanisms.
  • Biophysics was historically used for hit validation and lead optimization.
  • Advancements in biophysics offer increased throughput and sensitivity for earlier applications.

Purpose of the Study:

  • To provide an overview of biophysics applications in early drug discovery.
  • To highlight biophysics' role in reagent quality assessment, assay validation, and compound characterization.
  • To discuss strategies for hit validation using diverse biophysical methods.

Main Methods:

  • Utilizing biophysical techniques for reagent quality control in screening assays.
  • Applying biophysics to validate tool compounds and assess screening assay integrity.
  • Employing various biophysical methods for hit validation to ensure method overlap and avoid resource waste.

Main Results:

  • Early application of biophysics is crucial for characterizing complex biological targets.
  • Biophysics facilitates the identification and classification of small molecules with allosteric or covalent interactions.
  • Integrating biophysics early increases the likelihood of discovering chemical leads with novel mechanisms.

Conclusions:

  • Biophysics is essential for early-stage drug discovery, particularly for complex targets.
  • The early use of biophysics improves the identification of compounds with novel mechanisms of action.
  • Future drug discovery will increasingly feature focused screens with biophysics as a primary readout.