O-linked triazolotriazines: potent and selective c-Met inhibitors

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Published on: October 17, 2025

Fang Chen1, Ying Wang, Jing Ai

  • 1Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, PR China.

Chemmedchem
|April 28, 2012
PubMed

Insights

Researchers discovered novel O-linked triazolotriazines that inhibit the HGF/c-Met pathway. Compound 6a shows potent and selective inhibition of c-Met, a promising target for anticancer drug discovery.

Area of Science:

  • Medicinal Chemistry
  • Oncology
  • Molecular Biology

Background:

  • The HGF/c-Met signaling pathway plays crucial roles in biological processes.
  • Dysregulation of this pathway is linked to poor prognosis in various cancers.
  • c-Met is a key therapeutic target for developing anticancer drugs.

Purpose of the Study:

  • To discover novel inhibitors of the c-Met pathway.
  • To identify potent and selective small molecules for anticancer drug discovery.

Main Methods:

  • Synthesis of a series of O-linked triazolotriazines.
  • Enzymatic assays to determine c-Met inhibitory activity.
  • Cellular assays to evaluate compound efficacy and selectivity.

Main Results:

  • Discovery of O-linked triazolotriazines with sub-nanomolar inhibition of c-Met.
  • Compound 6a demonstrated high potency and selectivity in both enzymatic and cellular assays.
  • The identified compounds represent promising leads for c-Met targeted cancer therapy.

Conclusions:

  • Novel O-linked triazolotriazines effectively inhibit c-Met activity.
  • Compound 6a is a highly potent and selective c-Met inhibitor.
  • These findings support the development of c-Met inhibitors for cancer treatment.

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