LIN28‐Targeting Chromenopyrazoles and Tetrahydroquinolines Induced Cellular Morphological Changes and Showed High Biosimilarity with BRD PROTACs
2025

Study of Chromenopyrazoles and Tetrahydroquinolines Targeting LIN28

publication Evidence: moderate

Author Information

Author(s): Jiang Mao, Giannino Nicole, Goebel Georg L., Sievers Sonja, Wu Peng

Primary Institution: Max Planck Institute of Molecular Physiology

Hypothesis

Can chromenopyrazoles and tetrahydroquinolines induce cellular morphological changes and show biosimilarity with BRD PROTACs?

Conclusion

The study found that selected LIN28-inactive compounds induced significant cellular morphological changes and showed high biosimilarity with certain biological clusters.

Supporting Evidence

  • Selected LIN28-inactive CMPs and THQs induced cellular morphological changes to different extents.
  • The most CPA-active CMPs exhibited high biosimilarity with the LCH and BET clusters.
  • CPA is useful in revealing hidden biological targets and mechanisms of action for biologically inactive small molecules.

Takeaway

The researchers looked at how certain chemicals affect cell shapes and found some that work similarly to known drugs, even if they don't target the same proteins.

Methodology

The study used a cell painting assay to measure cellular morphological changes induced by chromenopyrazoles and tetrahydroquinolines.

Limitations

The study did not validate whether compound 3 can induce BRD9/7 degradation.

Digital Object Identifier (DOI)

10.1002/cmdc.202400547

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