Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Drug Discovery: Overview

Drug Discovery: Overview

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...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Discovery of Proline-Based p300/CBP Inhibitors Using DNA-Encoded Library Technology in Combination with High-Throughput Screening.

Journal of medicinal chemistry·2022

Same author

The Discovery of Conformationally Constrained Bicyclic Peptidomimetics as Potent Hepatitis C NS5A Inhibitors.

ACS medicinal chemistry letters·2021

Same author

The structure and flavor of low sodium seasoning salts in combination with different sesame seed meal protein hydrolysate derived Maillard reaction products.

Food chemistry: X·2021

Same author

Modeling and visualizing the transport and retention of cationic and oxyanionic metals (Cd and Cr) in saturated soil under various hydrochemical and hydrodynamic conditions.

The Science of the total environment·2021

Same author

Cathepsin C Is Involved in Macrophage M1 Polarization via p38/MAPK Pathway in Sudden Cardiac Death.

Cardiovascular therapeutics·2021

Same author

Analysis of SARS-CoV-2 RNA Persistence across Indoor Surface Materials Reveals Best Practices for Environmental Monitoring Programs.

mSystems·2021

Search research articles

Related Experiment Video

Updated: Dec 28, 2025

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

Published on: January 21, 2020

DNA-Encoded Library Technology-Based Discovery, Lead Optimization, and Prodrug Strategy toward Structurally Unique

Wieslaw M Kazmierski¹, Bing Xia², John Miller¹

¹HIV Discovery Performance Unit, GlaxoSmithKline, Research Triangle Park, Durham, North Carolina 27709, United States.

Journal of Medicinal Chemistry

|February 20, 2020

Summary

Researchers discovered a new class of indoleamine 2,3-dioxygenase-1 (IDO1) inhibitors. Optimization led to a potent drug candidate with improved bioavailability and a unique binding mechanism.

More Related Videos

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Related Experiment Videos

Last Updated: Dec 28, 2025

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

Published on: January 21, 2020

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Area of Science:

Medicinal Chemistry
Drug Discovery
Biochemistry

Background:

Indoleamine 2,3-dioxygenase-1 (IDO1) is a key enzyme in immune regulation.
Targeting IDO1 offers a therapeutic strategy for various diseases.
Novel inhibitor classes are needed to overcome existing limitations.

Purpose of the Study:

To discover and develop novel indoleamine 2,3-dioxygenase-1 (IDO1) inhibitors.
To optimize initial hits for improved potency, pharmacokinetics, and bioavailability.
To identify a best-in-class IDO1 inhibitor with a favorable clinical profile.

Main Methods:

Affinity selection using an indole-based DNA-encoded library (DEL).
Structure-activity relationship (SAR) studies for lead optimization.
Prodrug strategy and salt screening to enhance bioavailability and solubility.
In vivo pharmacokinetic and pharmacodynamic assessments.

Main Results:

Discovery of a novel IDO1 inhibitor class starting from DEL screening.
Optimization yielded compound 11 with potent IDO1 inhibition and reduced clearance.
A phosphonooxymethyl prodrug (31) significantly improved bioavailability.
A crystalline tris-salt (32) demonstrated excellent solubility and bioavailability, overcoming formulation challenges.

Conclusions:

A novel, potent, and highly bioavailable IDO1 inhibitor (32) was developed.
Compound 32 exhibits best-in-class potential and a unique apo-IDO1 binding mode.
The developed prodrug and salt forms address key pharmacokinetic and formulation challenges.