Abstract
PIM-1 kinase is a member of the Ser/Thr kinases family, a well-studied therapeutic target for cancer therapy. The overexpression of PIM-1 is associated with prostate and breast cancer progression. Therapeutic targeting of PIM-1 disrupts crucial signaling pathways which contributes to cancer growth and resistance to conventional treatments. Here, we screened 100 natural compounds with known antioxidant properties to discover potential inhibitors of PIM-1. Two natural compounds, baicalin, and resveratrol, were investigated for their binding affinity and PIM-1 inhibitory potential using integrated computational and experimental approaches. Baicalin and resveratrol bind to PIM-1 with a docking score of −10.2 and −7.5 kcal/mol, respectively. Subsequently, fluorescence binding studies showed an excellent affinity with Ka values, 5.9 × 105 M−1 and 1.7 × 107 M−1 for baicalin and resveratrol, respectively. In addition, baicalin and resveratrol strongly inhibited the kinase activity of PIM-1 with IC50 values of 36.8 μM and 75 μM, respectively. Furthermore, both baicalin and resveratrol suppress the proliferation of cancer cells in a dose-dependent manner, with baicalin’s IC50 value for LNCaP and MDA-MB-231 cells being 34.8 µM and 35.6 µM, respectively, and resveratrol’s being 15.2 µM and 41.6 µM, respectively. We conclude that baicalin and resveratrol may be considered potent PIM-1 inhibitors, opening promising possibilities for the development of anti-cancer therapy via targeting PIM-1 for prostate and breast cancer. Finally, utilizing natural compounds that offer a safer alternative to drive the development of more potent, specific, and pharmacokinetically optimized derivatives for therapeutic targeting of emerging diseases.
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