Related Experiment Video

Updated: Aug 26, 2025

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
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Published on: May 14, 2016

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MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response

Jae Heun Chung1,2, Ho Jung Choi3,4, Yong Jung Kang3,4

  • 1Department of Internal Medicine, Pusan National University, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, Yangsan, 50612, South Korea. jhchung7942@gmail.com.

Experimental Hematology & Oncology
|October 8, 2022
PubMed
Abstract

Insights

MHY4571, a novel protein kinase A (PKA) inhibitor, effectively suppressed non-small cell lung cancer (NSCLC) cell proliferation and tumor growth in preclinical models. This PKA inhibitor shows promise for treating squamous NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The protein kinase A (PKA)/cAMP response element-binding protein (CREB) pathway is implicated in non-small cell lung cancer (NSCLC) cell proliferation.
  • Investigating novel therapeutic targets for NSCLC is crucial.

Purpose of the Study:

  • To evaluate the efficacy of MHY4571, a novel PKA inhibitor, in regulating the PKA-CREB pathway.
  • To determine the anti-tumor activity of MHY4571 in squamous NSCLC models.

Main Methods:

  • MHY4571 was designed as a PKA inhibitor with favorable in silico ADME properties.
  • In vitro studies utilized lung cancer cell lines, while in vivo efficacy was assessed in xenograft and orthotopic mouse models of squamous cell lung carcinoma.

Main Results:

  • MHY4571 dose-dependently inhibited PKA activity (>70%) and suppressed p-PKA and p-CREB expression.
  • MHY4571 reduced lung cancer cell viability, induced apoptosis, and significantly suppressed tumor growth in vivo.
  • PKA was identified as an upstream regulator of CREB phosphorylation, and MHY4571 synergized with cisplatin to induce apoptosis.

Conclusions:

  • MHY4571 demonstrates significant anti-tumor activity in preclinical models of squamous NSCLC.
  • MHY4571 may represent a potential therapeutic candidate for squamous cell lung cancer treatment.
Keywords:
CarcinogenesisCyclic AMP-Dependent Protein KinasesLung cancerMHY4571cAMP response element-binding protein

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