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

Pharmacogenomics: Identification of New Drug Targets

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...

You might also read

Related Articles

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

Sort by

Same author

Hippocampal communication with the anterior olfactory nucleus is necessary for context-dependent odor memory.

Behavioral neuroscience·2026

Same author

Protective Effect of Lower Limb Strength on Lower Limb Injuries Within International Sixes Lacrosse Players: A Nine-Month Prospective Study.

Journal of strength and conditioning research·2026

Same author

BMAL1 Drives Cisplatin Resistance in Non-Small Cell Lung Cancer Via Lactate-MRP1 Signaling Pathway.

Thoracic cancer·2026

Same author

Cognitive status and associated risk factors in high-risk older adults of China: a population-based cross-sectional study.

BMC geriatrics·2026

Same author

Targeting immunometabolic pathways with AZD1656 alleviates inflammation and metabolic dysfunction in type 2 diabetic cardiomyopathy.

Nature cardiovascular research·2026

Same author

Uncovering the oncogenic role of RTTN in melanoma pathogenesis and its therapeutic implications.

Molecular biology reports·2026

Search research articles

Related Experiment Video

Updated: Jun 19, 2026

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

Fragment-Based Screening Identifies New Quinazolinone-Based Inositol Hexakisphosphate Kinase (IP6K) Inhibitors.

Tyler Heitmann¹, Gangling Liao¹, Pablo de León¹

¹Lieber Institute for Brain Development, 855 North Wolfe Street, Baltimore, Maryland 21205, United States.

ACS Medicinal Chemistry Letters

|December 20, 2023

Summary

This summary is machine-generated.

Researchers discovered novel quinazolinone inhibitors for inositol hexakisphosphate kinase (IP6K), an enzyme implicated in metabolic and neurological disorders. These potent inhibitors show selectivity, offering potential therapeutic avenues.

More Related Videos

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

Screening for Thermotoga maritima Membrane-Bound Pyrophosphatase Inhibitors

Screening for Thermotoga maritima Membrane-Bound Pyrophosphatase Inhibitors

Published on: November 23, 2019

Related Experiment Videos

Last Updated: Jun 19, 2026

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

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

Screening for Thermotoga maritima Membrane-Bound Pyrophosphatase Inhibitors

Screening for Thermotoga maritima Membrane-Bound Pyrophosphatase Inhibitors

Published on: November 23, 2019

Area of Science:

Biochemistry
Medicinal Chemistry
Pharmacology

Background:

Inositol hexakisphosphate kinases (IP6Ks) play crucial roles in cellular signaling pathways.
IP6Ks are implicated in various physiological processes including glucose homeostasis, metabolic disorders, and neurological functions.
Dysregulation of IP6K activity is linked to diseases such as fatty liver disease, chronic kidney disease, and psychiatric disorders.

Purpose of the Study:

To identify novel small molecule inhibitors of inositol hexakisphosphate kinase (IP6K) using a high-throughput screening approach.
To explore the structure-activity relationships of identified quinazolinone-based inhibitors.
To assess the potency and isoform selectivity of the discovered inhibitors against IP6K1, IP6K2, and IP6K3.

Main Methods:

High-throughput fragment-based screening was utilized to identify initial hit compounds.
Molecular docking studies were performed to understand the binding interactions of inhibitors with the IP6K active site.
Structure-activity relationship (SAR) studies were conducted to optimize the quinazolinone core for improved potency and selectivity.

Main Results:

A series of quinazolinone derivatives were identified as potent inhibitors of IP6K.
Compounds demonstrated submicromolar inhibitory activity against IP6K.
The developed inhibitors exhibited interesting selectivity profiles, particularly for the IP6K1 isoform over IP6K2 and IP6K3.

Conclusions:

The study successfully identified novel quinazolinone-based IP6K inhibitors with significant potency and selectivity.
These findings provide a promising foundation for the development of therapeutic agents targeting IP6K for various diseases.
Further research into these inhibitors could elucidate their therapeutic potential in metabolic and neurological conditions.