ArticleExperimental hematology & oncology2022
MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer.
Article in Experimental hematology & oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 25 citations in OpenAlex.
- Comprehensive Analysis of the Predictive Value of Adenylate Cyclase 4 on Clinical Significance, Prognosis, and Immunotherapy in Human Cancers.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- PMFrontiers in public health · 2025Article
- Network Pharmacology and Molecular Docking Study on the Mechanism of the Therapeutic Effect of Strychni Semen in NSCLC.Biological procedures online · 2024Article
- LncRNA GTL2 regulates myoblast proliferation and differentiation via the PKA-CREB pathway in Duolang sheep.Zoological research · 2024Article
- Cordycepin Triphosphate as a Potential Modulator of Cellular Plasticity in Cancer via cAMP-Dependent Pathways: An In Silico Approach.International journal of molecular sciences · 2024Article
- RGS20 promotes non-small cell lung carcinoma proliferation via autophagy activation and inhibition of the PKA-Hippo signaling pathway.Cancer cell international · 2024Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Inhibition of PKA/CREB1 pathway confers sensitivity to ferroptosis in non-small cell lung cancer.Respiratory research · 2023Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC.
methodsWe designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma.
resultsMHY4571 inhibited PKA activity (> 70% inhibition) and suppressed the expression of p-PKA and p-CREB dose-dependently. MHY4571 treatment reduced lung cancer cell viability and promoted caspase 3-dependent apoptotic cell death. Orally administered MHY4571 significantly suppressed lung tumor growth in xenograft and orthotopic mouse models. PKA catalytic subunit alpha-silencing by siRNA (siPKA) strongly attenuated CREB phosphorylation; siCREB did not alter PKA protein levels or its phosphorylation, suggesting that PKA is an upstream regulator of CREB activity. MHY4571 acted synergistically with cisplatin (on co-treatment) to induce apoptotic cell death in lung cancer cells.
conclusionsOur results imply that MHY4571 may be a potential drug candidate for squamous cell lung cancer treatment.
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