Schulze, Volker K.; Klar, Ulrich; Kosemund, Dirk; Wengner, Antje M.; Siemeister, Gerhard; Stoeckigt, Detlef; Neuhaus, Roland; Lienau, Philip; Bader, Benjamin; Prechtl, Stefan; Holton, Simon J.; Briem, Hans; Marquardt, Tobias; Schirok, Hartmut; Jautelat, Rolf; Bohlmann, Rolf; Nguyen, Duy; Fernandez-Montalvan, Amaury E.; Boemer, Ulf; Eberspaecher, Uwe; Bruening, Michael; Doehr, Olaf; Raschke, Marian; Kreft, Bertolt; Mumberg, Dominik; Ziegelbauer, Karl; Brands, Michael; von Nussbaum, Franz; Koppitz, Marcus published the artcile< Treating Cancer by Spindle Assembly Checkpoint Abrogation: Discovery of Two Clinical Candidates, BAY 1161909 and BAY 1217389, Targeting MPS1 Kinase>, Recommanded Product: 6-Chloro-[1,2,4]triazolo[1,5-a]pyridin-2-amine, the main research area is cancer treatment MPS1 inhibitors HTS hits ATP binding site.
Inhibition of monopolar spindle 1 (MPS1) kinase represents a novel approach to cancer treatment: instead of arresting the cell cycle in tumor cells, cells are driven into mitosis irresp. of DNA damage and unattached/misattached chromosomes, resulting in aneuploidy and cell death. Starting points for our optimization efforts with the goal to identify MPS1 inhibitors were two HTS hits from the distinct chem. series “”triazolopyridines”” and “”imidazopyrazines””. The major initial issue of the triazolopyridine series was the moderate potency of the HTS hits. The imidazopyrazine series displayed more than 10-fold higher potencies; however, in the early project phase, this series suffered from poor metabolic stability. Here, we outline the evolution of the two hit series to clin. candidates BAY 1161909 (I) and BAY 1217389 (II), and reveal how both clin. candidates bind to the ATP site of MPS1 kinase, while addressing different pockets utilizing different binding interactions, along with their synthesis and preclin. characterization in selected in vivo efficacy models.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 1239647-60-9 belongs to class triazoles, and the molecular formula is C6H5ClN4, Recommanded Product: 6-Chloro-[1,2,4]triazolo[1,5-a]pyridin-2-amine.
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics