Category: 851435-28-4

Luo, Zhibo published the artcileDiscovery and optimization of selective RET inhibitors via scaffold hopping, Application of 2-Chloro-6-methyl-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine, the publication is Bioorganic & Medicinal Chemistry Letters (2021), 128149, database is CAplus and MEDLINE.

Aberrant alterations of rearranged during transfection (RET) have been identified as actionable drivers of multiple cancers, including thyroid carcinoma and lung cancer. Currently, several approved multikinase inhibitors such as vandetanib and cabozantinib demonstrate clin. activity in patients with RET-rearranged or RET-mutant cancers. However, the observed response rates are only modest and the ‘off-target’ toxicities resulted from the inhibition of other kinases is also a concern. Herein, we designed and synthesized a series of RET inhibitors based on the structure of selective RET inhibitor BLU-667 and investigated their biol. activities. We identified compound I as a novel potent and selective RET inhibitor with improved drug-like properties. Compound I exhibits a selective inhibitory profile with an inhibitory concentration 50 (IC₅₀) of 1.29 nM for RET and 1.97 (RET V804M) or 0.99 (RET M918T) for mutant RETs. The proliferation of Ba/F3 cells transformed with NSCLC related KIF5B-RET fusion was effectively suppressed by compound I (IC₅₀ = 19 nM). Addnl., compound 9 displayed less ‘off-target’ effects than BLU-667. In mouse xenograft models, compound I repressed tumor growth driven by KIF5B-RET-Ba/F3 cells in a dose-dependent manner. Based on its exceptional kinase selectivity, good potency and high exposure in tumor tissues, compound 9 represents a promising lead for the discovery of RET directed therapeutic agents and the study of RET-driven tumor biol.

Bioorganic & Medicinal Chemistry Letters published new progress about 851435-28-4. 851435-28-4 belongs to pyrazoles-derivatives, auxiliary class Imidazole,Pyrimidine,Chloride,Amine, name is 2-Chloro-6-methyl-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine, and the molecular formula is C9H10ClN5, Application of 2-Chloro-6-methyl-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Robke, Lucas published the artcilePhenotypic Identification of a Novel Autophagy Inhibitor Chemotype Targeting Lipid Kinase VPS34, HPLC of Formula: 851435-28-4, the publication is Angewandte Chemie, International Edition (2017), 56(28), 8153-8157, database is CAplus and MEDLINE.

Autophagy is a critical regulator of cellular homeostasis and metabolism Interference with this process is considered a new approach for the treatment of disease, in particular cancer and neurol. disorders. Therefore, novel small-mol. autophagy modulators are in high demand. We describe the discovery of autophinib, a potent autophagy inhibitor with a novel chemotype. Autophinib was identified by means of a phenotypic assay monitoring the formation of autophagy-induced puncta, indicating accumulation of the lipidated cytosolic protein LC3 on the autophagosomal membrane. Target identification and validation revealed that autophinib inhibits autophagy induced by starvation or rapamycin by targeting the lipid kinase VPS34.

Angewandte Chemie, International Edition published new progress about 851435-28-4. 851435-28-4 belongs to pyrazoles-derivatives, auxiliary class Imidazole,Pyrimidine,Chloride,Amine, name is 2-Chloro-6-methyl-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine, and the molecular formula is C9H10ClN5, HPLC of Formula: 851435-28-4.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics