Gunasekaran, Pethaiah Yim, Min Su Ahn, Mija Soung, Nak-Kyun Park, Jung-Eun Kim, Jaehi Bang, Geul Shin, Sang Chul Choi, Joonhyeok Kim, Minkyoung Kim, Hak Nam Lee, Young-Ho Chung, Young-Ho Lee, Kyeong Kim, Eunice EunKyeong Jeon, Young-Ho Kim, Min Ju Lee, Kyeong-Ryoon Kim, Bo-Yeon Lee, Kyung S. Ryu, Eun Kyoung Bang, Jeong Kyu 2024-01-19T16:01:07Z 2024-01-19T16:01:07Z 2021-09-02 2020-12 0022-2623 https://pubs.kist.re.kr/handle/201004/117690 Polo-like kinase-1 (Plk1) plays a key role in mitosis and has been identified as an attractive anticancer drug target. Plk1 consists of two drug-targeting sites, namely, N-terminal kinase domain (KD) and C-terminal polo-box domain (PBD). As KD-targeting inhibitors are associated with severe side effects, here we report on the pyrazole-based Plk1 PBD inhibitor, KBJK557, which showed a remarkable in vitro anticancer effect by inducing Plk1 delocalization, mitotic arrest, and apoptosis in HeLa cells. Further, in vivo optical imaging analysis and antitumorigenic activities in mouse xenograft models demonstrate that KBJK557 preferentially accumulates in cancer cells and selectively inhibits cancer cell proliferation. Pharmacokinetic profiles and partition coefficients suggest that KBJK557 was exposed in the blood and circulated through the organs with an intermediate level of clearance (t(1/2), 7.73 h). The present investigation offers a strategy for specifically targeting cancer using a newly identified small-molecule inhibitor that targets the Plk1 PBD. English AMER CHEMICAL SOC Development of a Polo-like Kinase-1 Polo-Box Domain Inhibitor as a Tumor Growth Suppressor in Mice Models Article 10.1021/acs.jmedchem.0c01451 1 JOURNAL OF MEDICINAL CHEMISTRY, v.63, no.23, pp.14905 - 14920 JOURNAL OF MEDICINAL CHEMISTRY 63 23 14905 14920 N scie scopus 000599531500039 2-s2.0-85096855934 Chemistry, Medicinal Pharmacology & Pharmacy Article PLK1 kinase inhibitor mouse model apoptosis