Kim, Minhee Yoon, Jihyeon Choi, Jun Young Park, Geumi Lee, Jae-Eon Lee, Gwi Bin Choi, Byeong Wook Kim, Pyeongkeun Kim, Hail Oh, Chang-Myung Bae, Myung Ae Kim, Seong Soon Lee, Eun Young Lee, Hyeok Jae Kim, Yunmin Kim, Hyun Woo Lee, Hohjai Jeon, Yong Hyun Ahn, Jin Hee 2025-01-20T08:30:36Z 2025-01-20T08:30:36Z 2025-01-17 2025-01 0022-2623 https://pubs.kist.re.kr/handle/201004/151630 Colorectal cancer is a prevalent and prominent contributor to global cancer-related fatalities with challenges in drug resistance and metastasis. Recent research highlights the potential relationship between serotonin and cancer. 5-Hydroxytryptamine receptor 2A (HTR2A) mRNA expression in colorectal cancer cells was found to be notably elevated compared to that in normal colon cells. We therefore attempted to synthesize and evaluate HTR2A antagonists to find peripherally acting anticancer agents. Among them, 15f showed good in vitro activity (IC50: 42.79 nM). 15f revealed good liver microsomal stability, without significant CYP inhibition and limited blood-brain barrier penetration. 15f also exerted selective cytotoxic effects against various colorectal cancer cells but not normal cells. 15f induced sub-G1 cell cycle arrest and apoptosis in colorectal cancer cells via the activation of p53/p21/caspase 3 signaling. In vivo treatment with 15f led to a marked delay in tumor growth in a colorectal cancer model in a dose-dependent manner. English American Chemical Society Synthesis and Biological Evaluation of Peripheral HTR2A Antagonists for Colorectal Cancer Article 10.1021/acs.jmedchem.4c02458 1 Journal of Medicinal Chemistry, v.68, no.2, pp.1716 - 1730 Journal of Medicinal Chemistry 68 2 1716 1730 N scie scopus 001390585600001 2-s2.0-85214357151 Chemistry, Medicinal Pharmacology & Pharmacy Article 5-HT2A RECEPTOR SEROTONIN PIMAVANSERIN