Novel Therapeutic Inhibitors Having Sugar Moiety Targeting HER2/EGFR as Anticancer Agent
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Authors
Solanki, Juhi
Shena, Aleksia
Gardison, Jean
Issue Date
2022-03-30
Type
Other
Language
en
Keywords
Anticancer agent , Small-molecule inhibitors , Sugar moiety , HER2 , EGFR
Alternative Title
Abstract
Several effective small-molecule inhibitors of HER2 or EGFR have been developed to treat metastatic cancer, and some of those drugs are dual HER2/EGFR inhibitors. To investigate the mechanism of the dual inhibition of the receptor tyrosine kinases HER2 and EGFR1, we carried out virtual screening for benzimidazole derivatives having sugar moiety. Based upon virtual screening and HER2/EGR1 assays data simulation, we confirmed and chosen the benzimidazole skeleton which NO2 functional groups as a key skeleton for the dual inhibition towards HER2/EGFR1 (8.81 µM, Figure 6) to design novel tyrosine kinases inhibitors. After selection of the core skeleton, we designed our novel inhibitors, targeting both HER2/ EGFR1 and having a benzimidazole skeleton including a sugar moiety as aiming to balance their hydrophilic and hydrophobic properties and to increase cell penetration including the pharmacokinetics properties. We are investigating the synthesis of target agent (T-1) and biological properties of these agents against cancer cell line.