Yi-Min Liu1, Chun-Han Chen2, Teng-Kuang Yeh3, Jing-Ping Liou1,4. 1. TMU Biomedical Commercialization Center, Taipei Medical University, Taipei, Taiwan. 2. Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 3. Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan. 4. School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Abstract
Aim: Bladder cancer is a highly recurrent urologic malignancy with limited treatment approaches. Previously, we reported compound 11 is a FGFR3 inhibitor with significant antibladder cancer activity. Materials & methods: In this study, a series of 7H-pyrrolo-[2,3-d]pyrimidine derivatives were synthesized through ring formation and modification of compound 11 for anticancer activity evaluation. Results: Compound 13i is the most effective agent against human RT-112 bladder cancer cells. Notably, 13i strongly inhibits CK1δ without affecting FGFR3 activity. We generated 13i HCl to increase solubility and showed profound cell cycle accumulation at the sub-G1 phase and apoptosis in CK1δ-overexpressed bladder and ovarian cancer cells. Conclusion: These results indicate that compound 13i could be a lead compound for further development of novel anticancer agents.
Aim: Bladder cancer is a highly recurrent urologic malignancy with limited treatment approaches. Previously, we reported compound 11 is a FGFR3 inhibitor with significant antibladder cancer activity. Materials & methods: In this study, a series of 7H-pyrrolo-[2,3-d]pyrimidine derivatives were synthesized through ring formation and modification of compound 11 for anticancer activity evaluation. Results: Compound 13i is the most effective agent against human RT-112 bladder cancer cells. Notably, 13i strongly inhibits CK1δ without affecting FGFR3 activity. We generated 13i HCl to increase solubility and showed profound cell cycle accumulation at the sub-G1 phase and apoptosis in CK1δ-overexpressed bladder and ovarian cancer cells. Conclusion: These results indicate that compound 13i could be a lead compound for further development of novel anticancer agents.