Pawara, Rahul published the artcileDesign and synthesis of the novel, selective WZ4002 analogue as EGFR-L858R/T790M tyrosine kinase inhibitors for targeted drug therapy in non-small-cell lung cancer (NSCLC), SDS of cas: 67914-60-7, the publication is Journal of Molecular Structure (2022), 132313, database is CAplus.
To conquer the drug-resistance of first-generation EGFR (epidermal growth factor receptor) kinase inhibitors and second-generation inhibitors’ non-selective toxicities in Non-Small Cell Lung Cancer (NSCLC) patients, a series of WZ4002 derivatives I [R1 = 4-fluorophenyl, 3,4-dichlorophenyl, 4-bromophenyl, etc.; R2 = 3-CH2=CHC(O)NHC6H4, 4-MeC(O)-N(CH2)2N-C6H4, 3-ClCH2C(O)NHC6H4, etc.] were discovered as novel double mutant EGFR-L858R/T790M TK inhibitors. This objective was attained by employing structure-based drug design and traditional optimization strategies based on the WZ4002 scaffold. Among the synthesized compounds I, representative compounds I [R1 = 4-chloro-3-fluorophenyl, 4-bromophenyl; R2 = 3-CH2=CHC(O)-N(CH2)2N-C6H4] displayed significant anti-proliferative activity on the Gefitinib-resistant cell line NCI-H1975, with an IC50 value of 0.179μM and 0.173μM, resp. Also, these compounds exhibited moderate anti-proliferative activity against the A549 cell, with an IC50 of 0.550μM and 0.528μM resp., suggesting their improved selectivity over the mutant EGFR-L858R/T790M. Excitingly, both these compounds showed significant inhibition of the double mutant EGFR-L858R/T790M TK with an IC50 value of 0.0063μM and 0.0060μM, resp. The IC50 values of both the promising compounds against the HepG2 cell line were more than 1μM, indicating safety for normal cells. Covalent docking and MD simulation further confirm their irreversible binding mode with the target protein. These results demonstrate that compounds I [R1 = 4-chloro-3-fluorophenyl, 4-bromophenyl; R2 = 3-CH2=CHC(O)-N(CH2)2N-C6H4] would be promising lead compound-targeting double mutant EGFR-L858R/T790M TK.
Journal of Molecular Structure published new progress about 67914-60-7. 67914-60-7 belongs to piperazines, auxiliary class Piperazine,Benzene,Phenol,Amide, name is 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, and the molecular formula is C12H16N2O2, SDS of cas: 67914-60-7.
Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics