Discovery of Novel Dual Mechanism of Action Src Signaling and Tubulin Polymerization Inhibitors (KX2-391 and KX2-361) was written by Smolinski, Michael P.;Bu, Yahao;Clements, James;Gelman, Irwin H.;Hegab, Taher;Cutler, David L.;Fang, Jane W. S.;Fetterly, Gerald;Kwan, Rudolf;Barnett, Allen;Lau, Johnson Y. N.;Hangauer, David G.. And the article was included in Journal of Medicinal Chemistry in 2018.Category: pyridine-derivatives This article mentions the following:
The discovery of potent, peptide site directed, tyrosine kinase inhibitors has remained an elusive goal. Herein we describe the discovery of two such clin. candidates that inhibit the tyrosine kinase Src. Compound 1 is a phase 3 clin. trial candidate that is likely to provide a first in class topical treatment for actinic keratosis (AK) with good efficacy and dramatically less toxicity compared to existing standard therapy. Compound 2 is a phase 1 clin. trial candidate that is likely to provide a first in class treatment of malignant glioblastoma and induces 30% long-term complete tumor remission in animal models. The discovery strategy for these compounds iteratively utilized mol. modeling, along with the synthesis and testing of increasingly elaborated proof of concept compounds, until the final clin. candidates were arrived at. This was followed with mechanism of action (MOA) studies that revealed tubulin polymerization inhibition as the second MOA. In the experiment, the researchers used many compounds, for example, Methyl 2-(5-bromopyridin-2-yl)acetate (cas: 917023-06-4Category: pyridine-derivatives).
Methyl 2-(5-bromopyridin-2-yl)acetate (cas: 917023-06-4) belongs to pyridine derivatives. The pyridine ring occurs in many important compounds, including agrochemicals, pharmaceuticals, and vitamins. One of the examples of pyridines is the well-known alkaloid lithoprimidine, which is an A3 adenosine receptor antagonist and N,N-dimethylaminopyridine (DMAP) analog, commonly used in organic synthesis.Category: pyridine-derivatives