Abstract
Aim: P38α plays a crucial role in the development of castration-resistant prostate cancer. Discovering novel inhibitors of P38α offers potential for the development of new anticancer drugs. Methods & results: Compounds from the Chemdiv and Enamine virtual libraries were filtered to construct the P38α inhibitor-like library. A total of 58 new P38α inhibitors were discovered via virtual screening; these included three compounds (compound 1, 5, 9) with kinase IC50 of below 10 μM. In vitro, these three compounds have the potential to suppress the viabilities of prostate cancer cell lines, however, only compound 9 can inhibit the proliferation and migration of prostate cancer cells. Conclusion: The potent compounds discovered in this study demonstrate anticancer functions by targeting the P38α mitogen-activated protein kinases signaling pathway and are worthy of further investigation.
Supplementary data
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Acknowledgments
The authors appreciate Ling Wang from South China University of Technology for providing them with some of the software needed for virtual screening described in this manuscript.
Financial & competing interests disclosure
This work was supported by grant from Guangdong Science and Technology Department (no: 2017B030314026). This work was supported by the National Natural Science Foundation of China (no: 81702527), Natural Science Foundation of Guangdong (no: 2015A030310091, no: 2016A030313185) and the Medical Scientific Research Foundation of Guangdong (no: A2015027) to K Li. This work was supported by The National Natural Science Foundation of China (no: 81472382; 81672550), the Guangdong Province Natural Science Foundation (no: 2014A030313079), the Fundamental Research Funds for the Central Universities (no: 14ykpy19), Guangdong Province Science and Technology for Social Development Project (no: 2013B021800107; 2017A020215018), Guangzhou City in 2015 scientific research projects (no: 201510010298), International Science and technology cooperation project of Guangdong province science and technology plan (no: 2016A050502020) to H Huang. This work was supported by China Scholarship Council to K Li and H Huang; the National Natural Science Foundation of China (no: 81772733); Guangdong scientific research projects (no: 2016A020215011); Guangzhou City scientific research projects (no: 201605130835264) to Z Guo. This work was supported by The National Science Foundation for Young Scientists of China (no: 81802527) to Y Lai. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.