The IκB Kinase Inhibitor ACHP Targets the STAT3 Signaling Pathway in Human Non-Small Cell Lung Carcinoma Cells

Lee, Jong Hyun and Mohan, Chakrabhavi Dhananjaya and Basappa, Salundi and Shobith, R. and Chinnathambi, Arunachalam and Alahmadi, Tahani Awad and Alharbi, Sulaiman Ali and Kumar, Alan Prem and Sethi, Gautam and Ahn, Kwang Seok and Rangappa, K. S (2019) The IκB Kinase Inhibitor ACHP Targets the STAT3 Signaling Pathway in Human Non-Small Cell Lung Carcinoma Cells. Biomolecules, 9 (12).

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Official URL: https://www.mdpi.com/2218-273X/9/12/875

Abstract

STAT3 is an oncogenic transcription factor that regulates the expression of genes which are involved in malignant transformation. Aberrant activation of STAT3 has been observed in a wide range of human malignancies and its role in negative prognosis is well-documented. In this report, we performed high-throughput virtual screening in search of STAT3 signaling inhibitors using a cheminformatics platform and identified 2-Amino-6-2-(Cyclopropylmethoxy)-6-Hydroxyphenyl-4-Piperidin-4-yl Nicotinonitrile (ACHP) as the inhibitor of the STAT3 signaling pathway. The predicted hit was evaluated in non-small cell lung cancer (NSCLC) cell lines for its STAT3 inhibitory activity. In vitro experiments suggested that ACHP decreased the cell viability and inhibited the phosphorylation of STAT3 on Tyr705 of NSCLC cells. In addition, ACHP imparted inhibitory activity on the constitutive activation of upstream protein tyrosine kinases, including JAK1, JAK2, and Src. ACHP decreased the nuclear translocation of STAT3 and downregulated its DNA binding ability. Apoptosis was evidenced by cleavage of caspase-3 and PARP with the subsequent decline in antiapoptotic proteins, including Bcl-2, Bcl-xl, and survivin. Overall, we report that ACHP can act as a potent STAT3 signaling inhibitor in NSCLC cell lines.

Item Type: Article
Subjects: B Life Science > Molecular Biology
Divisions: Department of > Chemistry
Depositing User: C Swapna Library Assistant
Date Deposited: 20 Nov 2025 09:27
Last Modified: 20 Nov 2025 09:27
URI: http://eprints.uni-mysore.ac.in/id/eprint/17947

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