Elwaie, Tamer A.; Abbas, Safinaz E.; Aly, Enayat I.; George, Riham F.; Ali, Hamdy; Kraiouchkine, Nikolai; Abdelwahed, Khaldoun S.; Fandy, Tamer E.; El Sayed, Khalid A.; Abd Elmageed, Zakaria Y.; Ali, Hamed I. published their research in Journal of Medicinal Chemistry on December 24 ,2020. The article was titled 《HER2 Kinase-Targeted Breast Cancer Therapy: Design, Synthesis, and In Vitro and In Vivo Evaluation of Novel Lapatinib Congeners as Selective and Potent HER2 Inhibitors with Favorable Metabolic Stability》.Product Details of 350-30-1 The article contains the following contents:
HER2 kinase as a well-established target for breast cancer (BC) therapy is associated with aggressive clin. outcomes; thus, herein we present structural optimization for HER2-selective targeting. HER2 profiling of the developed derivatives demonstrated potent and selective inhibitions (IC50: 5.4-12 nM) compared to lapatinib (IC50: 95.5 nM). Favorably, 17d exhibited min. off-target kinase activation. NCI-5-dose screening revealed broad-spectrum activities (GI50: 1.43-2.09μM) and 17d had a remarkable selectivity toward BC. Our compounds revealed significant selective and potent antiproliferative activities (~20-fold) against HER2+ (AU565, BT474) compared to HER2(-) cells. At 0.1 IC50, 15i, 17d, and 25b inhibited pERK1/2 and pAkt by immunoblotting. Furthermore, 17d demonstrated potent in vivo tumor regression against the BT474 xenograft model. Notably, a metastasis case was observed in the vehicle but not in the test mice groups. CD-1 mice metabolic stability assay revealed high stability and low intrinsic clearance of 17d (T1/2 > 145 min and CLint(mic) < 9.6 mL/min/kg). The experimental process involved the reaction of 3-Chloro-4-fluoronitrobenzene(cas: 350-30-1Product Details of 350-30-1)
3-Chloro-4-fluoronitrobenzene(cas: 350-30-1) belongs to organochlorine compounds. The wide structural variety and divergent chemical properties of organochlorides lead to a broad range of names, applications, and properties.Product Details of 350-30-1 Organochlorine compounds have wide use in many applications, though some are of profound environmental concern, with TCDD being one of the most notorious.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics