AI Article Synopsis
- The article discusses the identification of strong inhibitors for Polo-like kinase 1 (PLK1), focusing on a compound known as 12c (MLN0905) derived from benzolactam.
- Optimization efforts led to the creation of 12c, which is effective when taken orally.
- Experiments in mice showed that 12c can significantly inhibit tumor growth or even cause tumor regression in human colon cancer models.
Article Abstract
This article describes the discovery of a series of potent inhibitors of Polo-like kinase 1 (PLK1). Optimization of this benzolactam-derived chemical series produced an orally bioavailable inhibitor of PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration of 12c to tumor bearing nude mice. A subsequent efficacy study in nude mice achieved tumor growth inhibition or regression in a human colon tumor (HT29) xenograft model.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm2011172 | DOI Listing |
Publication Analysis
Top Keywords
orally bioavailable
8
polo-like kinase
8
nude mice
8
discovery potent
4
potent orally
4
bioavailable benzolactam-derived
4
benzolactam-derived inhibitor
4
inhibitor polo-like
4
kinase mln0905
4
mln0905 article
4
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!