Zhang, Jin published the artcileDesign, synthesis and biological evaluation of 1H-pyrazolo [3,4-d]pyrimidine derivatives as PAK1 inhibitors that trigger apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells, Synthetic Route of 73874-95-0, the main research area is pyrazolopyrimidine preparation PAK1 inhibitor mol docking; Apoptosis; Breast cancer; High-throughput screening; Migration; PAK1 inhibitor.
P21-activated kinase 1 (PAK1) is associated with cell proliferation, survival and migration. Deregulation of PAK1 activity is involved in various human diseases, including cancer, inflammation, and neurol. disorders. Using a high-throughput virtual screening, we identified the 1H-pyrazolo [3,4-d]pyrimidine scaffold as a promising lead for targeting PAK1. A novel potent PAK1 inhibitor, (I), was discovered, which presented an IC50 value of 174 nM with a good selectivity. In addition, compound Icould inhibit PAK1-ERK signaling to suppress MDA-MB-231 cells proliferation with an IC50 value of 3.48μM for 48 h. Subsequently, compound Iwas documented to induce cell apoptosis. Interestingly, according to the RNASeq-based analyses, substantiated that compound Iinduced significant ER-Stress, suppressed migration via FOXO3 activation, JNK1/2, ERK1/2 and AKT signaling inhibition. Together, these results demonstrate that compound Iis a novel PAK1 inhibitor triggering apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells, which may provide a candidate lead for the development of novel potent inhibitors of PAK1.
European Journal of Medicinal Chemistry published new progress about Acid chlorides Role: RCT (Reactant), RACT (Reactant or Reagent). 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Synthetic Route of 73874-95-0.
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem