Related Experiment Video

Updated: Apr 11, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.3K

Developing novel Lin28 inhibitors by computer aided drug design

Victor M Matias-Barrios1, Mariia Radaeva1, Graciella Rosellinny1

  • 1The Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.

Cell Death Discovery
|January 12, 2025
PubMed

Insights

Researchers discovered Ln268, a novel compound targeting Lin28 (a key regulator in cancer stem cells), to combat therapy-resistant tumors. This drug candidate inhibits Lin28 activity and shows promise for cancer treatment development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Lin28 is a critical regulator of cancer stem cell networks, driving therapy-resistant tumor progression.
  • Existing Lin28 inhibitors lack clinical approval, necessitating the search for novel therapeutic agents.

Purpose of the Study:

  • To discover and characterize novel compounds that inhibit Lin28 activity for potential cancer therapy.
  • To validate a computer-aided drug design (CADD) approach for identifying Lin28 inhibitors.

Main Methods:

  • Computer-aided drug design (CADD) was employed to identify potential Lin28 inhibitors.
  • Quantitative biochemical and biological assays were used to assess compound efficacy.
  • Nuclear magnetic resonance (NMR) spectroscopy confirmed the molecular interaction of the drug candidate with Lin28.

Main Results:

  • Ln268 was identified as a potent inhibitor that blocks Lin28 binding to RNA substrates and inhibits its activity.
  • Ln268 suppressed cancer cell proliferation and spheroid growth, with effects dependent on Lin28 expression.
  • NMR confirmed Ln268 perturbs the Lin28 zinc knuckle domain, validating the CADD approach.
  • Ln268 demonstrated synergy with conventional chemotherapy drugs.

Conclusions:

  • Ln268 is a promising drug candidate for targeting Lin28 in cancer therapy.
  • The study validates the use of CADD in discovering targeted cancer therapeutics.
  • Ln268 exhibits specific inhibitory effects and potential for combination therapy.

More Related Videos

Screening Traditional Chinese Medicine Compounds for Inhibiting UCHL3 Activity Based on Molecular Docking and Deubiquitinating Enzyme Probe Technology10:25

Screening Traditional Chinese Medicine Compounds for Inhibiting UCHL3 Activity Based on Molecular Docking and Deubiquitinating Enzyme Probe Technology

Published on: November 22, 2024

223
Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors10:29

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

Published on: May 9, 2025

344

Related Concept Videos

Structure-Activity Relationships and Drug Design01:28

Structure-Activity Relationships and Drug Design

Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
2.1K
Dosage Regimens: Designs and Approaches01:28

Dosage Regimens: Designs and Approaches

Designing a dosage regimen, which refers to the manner of drug administration, is a complex process involving the selection of drug dose, route, and frequency. This process is underpinned by pharmacokinetic parameters derived from tests and population averages. These parameters are then tailored to patient-specific variables such as diagnosis, demographics, and allergy status. Once therapy commences, therapeutic response monitoring is critical and achieved through clinical and physical...
562
Pharmacogenomics: Identification of New Drug Targets01:29

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...
91