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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2022.11
- 수록면
- 91 - 98 (8page)
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초록· 키워드
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PIM kinases, a family of serine/threonine kinases, are major downstream effectors of the Janus kinase/signal transducer and activator of transcription signaling cascade, which drive cell growth, proliferation, and metastasis in solid tumors and hematological cancers. Therefore, PIM kinases are potential targets for anticancer therapies. 2,4-Bis(2-aminopyrimidin-4-yl) phenol is a potential anticancer agent that targets the cyclin-dependent kinase family. As this compound showed submicromolar potency in a PIM-1 kinase assay, we designed 2-(2-aminopyrimidin-4-yl)phenol analogs as PIM kinase inhibitors. Systematic modifications at the 2- and 4- positions of the phenol ring led to the discovery of PIM kinase inhibitor 16, which showed sub-micromolar potency against PIM-2 and double-digit nanomolar potency against PIM-1 and PIM-3 isoforms. Based on molecular docking studies, compound 16 was predicted to bind to the adenosine triphosphate pocket of PIM-1 kinase with two hydrogen bonding interactions and hydrophobic interactions.
목차
ABSTRACT
1. Introduction
2. Experimental Methods
3. Results and Discussion
References
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