Category: 100959-51-1

Kohlmann, Anna published the artcileFragment Growing and Linking Lead to Novel Nanomolar Lactate Dehydrogenase Inhibitors, Formula: C7H6ClNO4, the main research area is preparation lactate dehydrogenase A inhibitor cancer.

Lactate dehydrogenase A (LDH-A) catalyzes the interconversion of lactate and pyruvate in the glycolysis pathway. Cancer cells rely heavily on glycolysis instead of oxidative phosphorylation to generate ATP, a phenomenon known as the Warburg effect. The inhibition of LDH-A by small mols. is therefore of interest for potential cancer treatments. We describe the identification and optimization of LDH-A inhibitors by fragment-based drug discovery. We applied ligand based NMR screening to identify low affinity fragments binding to LDH-A. The dissociation constants (Kd) and enzyme inhibition (IC50) of fragment hits were measured by surface plasmon resonance (SPR) and enzyme assays, resp. The binding modes of selected fragments were investigated by X-ray crystallog. Fragment growing and linking, followed by chem. optimization, resulted in nanomolar LDH-A inhibitors that demonstrated stoichiometric binding to LDH-A. Selected mols. inhibited lactate production in cells, suggesting target-specific inhibition in cancer cell lines.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 100959-51-1 belongs to class chlorides-buliding-blocks, name is 2-Chloro-5-methoxy-4-nitrophenol, and the molecular formula is C7H6ClNO4, Formula: C7H6ClNO4.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Czako, Barbara published the artcileDiscovery of IACS-9439, a Potent, Exquisitely Selective, and Orally Bioavailable Inhibitor of CSF1R, Related Products of chlorides-buliding-blocks, the main research area is discovery IACS 9439 preparation inhibitor CSF1R SAR anticancer.

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.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 100959-51-1 belongs to class chlorides-buliding-blocks, name is 2-Chloro-5-methoxy-4-nitrophenol, and the molecular formula is C7H6ClNO4, Related Products of chlorides-buliding-blocks.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics