Discovery of IACS-9439, a Potent, Exquisitely Selective, and Orally Bioavailable Inhibitor of CSF1R was written by Czako, Barbara;Marszalek, Joseph. R.;Burke, Jason P.;Mandal, Pijus;Leonard, Paul G.;Cross, Jason B.;Mseeh, Faika;Jiang, Yongying;Chang, Edward Q.;Suzuki, Erika;Kovacs, Jeffrey J.;Feng, Ningping;Gera, Sonal;Harris, Angela L.;Liu, Zhen;Mullinax, Robert A.;Pang, Jihai;Parker, Connor A.;Spencer, Nakia D.;Yu, Simon S.;Wu, Qi;Tremblay, Martin R.;Mikule, Keith;Wilcoxen, Keith;Heffernan, Timothy P.;Draetta, Giulio F.;Jones, Philip. And the article was included in Journal of Medicinal Chemistry in 2020.Application of 626-64-2 This article mentions the following:
Tumor-associated macrophages (TAMs) have a significant presence in the tumor stroma across multiple human malignancies and are believed to be beneficial to tumor growth. Targeting CSF1R has been proposed as a potential therapy to reduce TAMs, especially the protumor, immune-suppressive M2 TAMs. Addnl., the high expression of CSF1R on tumor cells has been associated with poor survival in certain cancers, suggesting tumor dependency and therefore a potential therapeutic target. The CSF1-CSF1R signaling pathway modulates the production, differentiation, and function of TAMs; however, the discovery of selective CSF1R inhibitors devoid of type III kinase activity has proven to be challenging. We discovered a potent, highly selective, and orally bioavailable CSF1R inhibitor, IACS-9439 (I). Treatment with I led to a dose-dependent reduction in macrophages, promoted macrophage polarization toward the M1 phenotype, and led to tumor growth inhibition in MC38 and PANC02 syngeneic tumor models. In the experiment, the researchers used many compounds, for example, Pyridin-4-ol (cas: 626-64-2Application of 626-64-2).
Pyridin-4-ol (cas: 626-64-2) belongs to pyridine derivatives. Pyridine’s the lone pair does not contribute to the aromatic system but importantly influences the chemical properties of pyridine, as it easily supports bond formation via an electrophilic attack. Several pyridine derivatives play important roles in biological systems. While its biosynthesis is not fully understood, nicotinic acid (vitamin B3) occurs in some bacteria, fungi, and mammals.Application of 626-64-2