Related Experiment Video

Updated: Jan 7, 2026

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
05:33

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

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Design, synthesis and biological evaluation of macrocyclic NTRK heterobifunctional degraders

Corey Anderson1, Jennifer Han-Chun Tsai1, Oscar Ingham1

  • 1C4 Therapeutics, 490 Arsenal Way, Suite 120, Watertown, MA 02472, USA.

Bioorganic & Medicinal Chemistry Letters
|January 3, 2026
PubMed

Insights

New NTRK BiDAC™ degraders were designed to target resistant tumors. These novel compounds offer a promising therapeutic strategy against cancers driven by NTRK gene fusions, addressing limitations of current treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Aberrant NTRK gene fusions drive various adult and pediatric tumors.
  • Approved NTRK inhibitors show clinical success but face resistance.
  • Emergence of resistance mutations necessitates novel therapeutic approaches.

Purpose of the Study:

  • To design, synthesize, and evaluate novel NTRK BiDAC™ degraders.
  • To develop new therapies targeting NTRK-driven tumors with resistance mutations.

Main Methods:

  • Design of novel NTRK BiDAC™ degraders.
  • Synthesis of macrocyclic ligands targeting the mutant active NTRK.
  • Evaluation of the designed degraders.

Main Results:

  • Successful design and synthesis of novel NTRK BiDAC™ degraders.
  • Development of macrocyclic ligands capable of targeting mutant active NTRK.
  • Demonstrated potential of these degraders as a new therapeutic strategy.

Conclusions:

  • NTRK BiDAC™ degraders represent a promising new class of drugs.
  • These degraders can overcome resistance mechanisms associated with NTRK inhibitors.
  • Further development could lead to effective treatments for NTRK-fusion-driven cancers.
Keywords:
Exit vector analysisHeterobifunctional degradersMacrocyclesNTRKProtein degradationTernary complex

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