Retrometabolic Approach for Designing Personalized Anti- Cancer Drug Molecules for Controlling Breast Cancer Resulted by BRCA1 Mutations

Conclusion: The people with the genetic signatures, rs28897696 are more prone to breast cancer resulted by the BRCA1 mutation. For the PARP inhibition analysis, Human ARTD1 (PARP1) catalytic domain in complex with inhibitor Rucaparib (4RV6) has been considered. The inhibitors of PARP1 and BRCA1 have been designed in the retrometabolic manner from metabolites of chlorambucil and active/ inactive metabolites present in human body. The evolved molecules, 8-(5-acetyl-2-hydroxyphenoxy)-4-amino-3-hydroxy-5-methyloctanoic acid, 4-amino-3-hydroxy-9-(4-hydroxy-3-methoxyphenyl)-5,5-dimethyl-9-oxononanoic acid and 8-(5-acetyl-2-hydroxyphenoxy)-4-amino-3-hydroxy-5,5-dimethyloctanoic acid are found to be promising anti-breast cancer drugs with comparatively low side effects and more personalization subject to further in vivo and clinical evaluations.
Source: Current Pharmacogenomics and Personalized Medicine - Category: Genetics & Stem Cells Source Type: research