Related Experiment Video

Updated: Jun 18, 2026

A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors
10:28

A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors

Published on: August 17, 2019

Structure-Based Search for Novel Creatine Transporter Inhibitors

Dorota Stary1,2,3, Ali El-Kasaby4, Danila Boytsov4

  • 1Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Cracow, Poland.

ACS Medicinal Chemistry Letters
|June 17, 2026
PubMed

Insights

Researchers developed a computational method to discover inhibitors for the creatine transporter 1 (CT1), a protein linked to neurological disorders and cancer. Compound 11 and other tested molecules showed promising CT1 inhibitory activity, paving the way for new drug designs.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Computational Chemistry

Background:

  • Creatine transporter 1 (CT1, SLC6A8) is crucial for cellular energy regulation.
  • CT1 dysfunction is implicated in neurological disorders and cancer progression.
  • Lack of structural data has hindered the rational design of CT1 inhibitors.

Purpose of the Study:

  • To develop a computational framework for identifying CT1 inhibitors.
  • To validate computational models with experimental testing.
  • To support structure-based drug design for CT1.

Main Methods:

  • Construction of CT1 homology models in distinct transport states.
  • Integration of models into a structure-based virtual screening workflow.
  • In vitro testing of top-ranked compounds, including compound 11, tiagabine (13), and analogue 16.

Main Results:

  • Virtual screening identified 16 top-ranked compounds for in vitro testing.
  • Compound 11 demonstrated CT1 inhibitory activity with an IC50 comparable to ompenaclid.
  • Tiagabine (13) and analogue 16 were also found to inhibit CT1.
  • Retrospective analysis showed good agreement between homology models and reported cryo-EM structures.

Conclusions:

  • The study presents a successful computational-experimental framework for CT1 inhibitor discovery.
  • The findings facilitate future structure-based drug design targeting CT1.
  • Identified compounds provide starting points for developing novel therapeutics for CT1-related conditions.
Keywords:
creatine transporterdockingmolecular dynamicsstructure-based drug designvirtual screening

More Related Videos

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

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

Published on: January 22, 2019

Related Concept Videos

Secondary Active Transport01:32

Secondary Active Transport

One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme "pump" embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
The Significance of Membrane Transport01:44

The Significance of Membrane Transport

The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
ABC Transporters: Importer01:27

ABC Transporters: Importer

ATP-binding cassette or ABC transporters are a class of ATP-driven pumps that hydrolyze ATP to move solutes across the membrane. They can be grouped into importers and exporters. While exporters are present in all domains of life, importers exist only in bacteria and some plants.
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
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...
ABC Transporters: Exporter01:31

ABC Transporters: Exporter

ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...