Campos, Ludmila E. published the artcileSearching new structural scaffolds for BRAF inhibitors. An integrative study using theoretical and experimental techniques, COA of Formula: C6H8N2O2S, the publication is Bioorganic Chemistry (2019), 103125, database is CAplus and MEDLINE.
The identification of the V600E activating mutation in the protein kinase BRAF in around 50% of melanoma patients has driven the development of highly potent small inhibitors (BRAFi) of the mutated protein. To date, Dabrafenib and Vemurafenib, two specific BRAFi, have been clin. approved for the treatment of metastatic melanoma. Unfortunately, after the initial response, tumors become resistant and patients develop a progressive and lethal disease, making imperative the development of new therapeutic options. The main objective of this work was to find new BRAF inhibitors with different structural scaffolds than those of the known inhibitors. Our study was carried out in different stages; in the first step we performed a virtual screening that allowed us to identify potential new inhibitors. In the second step, we synthesized and tested the inhibitory activity of the novel compounds founded. Finally, we conducted a mol. modeling study that allowed us to understand interactions at the mol. level that stabilize the formation of the different mol. complexes. Our theor. and exptl. study allowed the identification of four new structural scaffolds, which could be used as starting structures for the design and development of new inhibitors of BRAF. Our exptl. data indicate that the most active compounds reduced significantly ERK1/2 phosphorylation, a measure of BRAF inhibition, and cell viability. Thus, from our theor. and exptl. results, we propose new substituted hydroxynaphthalenecarboxamides, N-(hetero)aryl-piperazinylhydroxyalkylphenylcarbamates, substituted piperazinylethanols and substituted piperazinylpropandiols as initial structures for the development of new inhibitors for BRAF. Moreover, by performing QTAIM anal., we are able to describe in detail the mol. interactions that stabilize the different Ligand-Receptor complexes. Such anal. indicates which portion of the different mols. must be changed in order to obtain an increase in the binding affinity of these new ligands.
Bioorganic Chemistry published new progress about 64987-16-2. 64987-16-2 belongs to thiazole, auxiliary class Thiazole,Amine,Ester, name is Methyl 2-(2-aminothiazol-4-yl)acetate, and the molecular formula is C6H8N2O2S, COA of Formula: C6H8N2O2S.
Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica