Phthalimide Derivative Shows Anti-angiogenic Activity in a 3D Microfluidic Model and No Teratogenicity in Zebrafish Embryos

In conclusion, our in vitro results suggest that all the synthetic Thalidomide analogs present a much lower effective dose with an anti-angiogenic function compared to Thalidomide and that C4 is the most effective. In vivo, C4 showed an enhanced anti-angiogenesis potency with reduced side effects compared to Thalidomide. Further investigation to elucidate the molecular pathways activated by C4 would be important for downstream drug development. This could involve investigating if Cereblon, the molecular target of Thalidomide and its chiral analogs Lenalidomide and Pomalidomide (Ito et al., 2010; Lopez-Girona et al., 2012), is also the molecular target of C4. Ethics Statement This study was carried out in accordance with the recommendations of the Singapore National Advisory on Laboratory Animal Research. The protocol was approved by the Singapore National Advisory on Laboratory Animal Research. Author Contributions GA, AP, RK, AM, and LS conceptualized the experimental assays. GA, AM, and LS performed the methodology. AM acquired the data. AM, GA, and AP analyzed the data. AM, ACat, and ACar performed the chemical synthesis. AM, GA, AP, and LS wrote the manuscript. CF, FC, and RK provided the resources. GA, AP, RK, FC, and AV supervised the study. Funding The research was supported by the National Research Foundation (NRF), Prime Minister’s Office, Singapore, under its CREATE program, Singapore-MIT Alliance for Research and Technology (SMART) BioSystems and Micro...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research