Giri R Gnawali, Koichi Okumura, Karolina Perez, Rosa Gallagher, Julia Wulfkuhle, Emanuel F Petricoin, Sathish Kumar Reddy Padi, Jeremiah Bearss, Zhiyong He, Wei Wang, Andrew S Kraft
Compound VBT-5445 was identified as an inhibitor to block the association of Pim and the protein Enhancer of Decapping 3 (EDC3), a Pim substrate, which normally functions to enhance the decapping of messenger RNA (mRNA). It was also shown to inhibit both the Pim and mTORC protein kinases. The activity of this compound class can be fine-tuned by structural modification. A series of VBT analogs were designed, synthesized, and evaluated. These compounds decrease the growth of multiple cancer types, including pancreas, prostate, breast, lung, and leukemia...
July 2022: Medicinal Chemistry Research