PB-10, a thiazolo[4,5-d] pyrimidine derivative, targets p21-activated kinase 4 in human colorectal cancer cells.

Ruijuan Li, Hanxun Wang, Jian Wang, Maosheng Cheng

Bioorganic & medicinal chemistry letters 2020 Jan 15

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Targeting p21-activated kinase 4 (PAK4) is a potential therapeutic strategy against human colorectal cancer (CRC). In this study, we synthesized a series of novel thiazolo[4,5-d]pyrimidine derivatives (PB-1-12) and identified PB-10 (PAK4 IC50 = 15.12 μM) as a potential and potent PAK4 inhibitor. Our results showed that PB-10 significantly suppressed the proliferation and colony formation of human CRC cells. PB-10 also arrested HCT-116 CRC cells at sub G0/G1 phase while promoting the expression of proapoptotic proteins. In addition, PB-10 inhibited migration, invasion, and adhesion as well as the PAK4 downstream signaling pathway in HCT-116 cells. Molecular docking analysis showed possible binding modes between PB-10 and PAK4. Our study provides a novel compound that may block the PAK4 signaling in CRC cells. Copyright © 2019 Elsevier Ltd. All rights reserved.

Citation

Ruijuan Li, Hanxun Wang, Jian Wang, Maosheng Cheng. PB-10, a thiazolo[4,5-d] pyrimidine derivative, targets p21-activated kinase 4 in human colorectal cancer cells. Bioorganic & medicinal chemistry letters. 2020 Jan 15;30(2):126807