Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Drug Discovery: Overview01:26

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

SARM1 base-exchange inhibitors induce SARM1 activation and neurodegeneration at low doses.

npj drug discovery·2026
Same author

How many protein pairs can we chemically target?

Drug discovery today·2026
Same author

ChemBang: Expanding the Chemical Space Around Small Molecules.

Molecular informatics·2026
Same author

SAFR: Enabling Fragment-Based Drug Discovery with a Synthetic Binding Pose Data Set.

Journal of chemical information and modeling·2026
Same author

A central somatotopic map of the fly leg supports spatially targeted grooming.

Current biology : CB·2026
Same author

AVRNT Associated With an Unusual Pathway Involving the Anterior LA Adjacent to Non-CS of AV.

JACC. Clinical electrophysiology·2026

Related Experiment Video

Updated: Jun 6, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

Fragment-based discovery of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors.

Peter Ray1, Jane Wright, Julia Adam

  • 1Discovery Research, MSD, Newhouse, Lanarkshire ML1 5SH, Scotland, UK. peter.ray@merck.com

Bioorganic & Medicinal Chemistry Letters
|December 15, 2010
PubMed
Summary

Researchers identified a novel Rho-kinase (ROCK-I) inhibitor, compound 23A, using fragment-based screening. This inhibitor shows comparable efficacy to existing ROCK-I drugs but with an improved pharmacokinetic profile in mice.

More Related Videos

Facile Preparation of 4-Substituted Quinazoline Derivatives
11:51

Facile Preparation of 4-Substituted Quinazoline Derivatives

Published on: February 15, 2016

Related Experiment Videos

Last Updated: Jun 6, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

Facile Preparation of 4-Substituted Quinazoline Derivatives
11:51

Facile Preparation of 4-Substituted Quinazoline Derivatives

Published on: February 15, 2016

Area of Science:

  • Medicinal Chemistry
  • Pharmacology
  • Biochemistry

Background:

  • Rho-kinase (ROCK-I) is a key regulator in cellular processes, and its inhibition is therapeutically relevant.
  • Fragment-based screening is an effective strategy for identifying novel drug leads.
  • A historical thrombin/Factor Xa building block was repurposed as a ROCK-I inhibitor.

Purpose of the Study:

  • To identify novel inhibitors of ROCK-I using fragment-based NMR screening.
  • To optimize initial fragment hits into potent and efficacious ROCK-I inhibitors.
  • To evaluate the pharmacokinetic properties of optimized ROCK-I inhibitors.

Main Methods:

  • Fragment-based NMR screening of a focused library.
  • Structure-guided fragment growth to generate isoquinolin-1-amine derivatives.
  • In vitro biochemical assays (ROCK-I IMAP assay) and cell-based assays.
  • Pharmacokinetic profiling in C57 mice.

Main Results:

  • Identification of compound 17A, a ROCK-I inhibitor, from a literature-focused library.
  • Synthesis and profiling of 6-substituted isoquinolin-1-amine derivatives.
  • Compound 23A demonstrated ROCK-I affinity, potency, and cell-based efficacy comparable to first-generation inhibitors with superior mouse PK.
  • Compound 23E showed improved potency but a poorer PK profile compared to 23A.

Conclusions:

  • Fragment-based drug discovery successfully yielded novel ROCK-I inhibitors.
  • Compound 23A represents a promising candidate with a balanced profile of efficacy and pharmacokinetics.
  • Further optimization of this series is feasible to enhance potency while maintaining favorable drug-like properties.