Synthetic Lethality Through the Lens of Medicinal Chemistry

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2020 Nov 2

PMID 33135887

Citations 15

Authors

Samuel H Myers

Jose Antonio Ortega

Andrea Cavalli

Affiliations

Soon will be listed here.

Abstract

Personalized medicine and therapies represent the goal of modern medicine, as drug discovery strives to move away from one-cure-for-all and makes use of the various targets and biomarkers within differing disease areas. This approach, especially in oncology, is often undermined when the cells make use of alternative survival pathways. As such, acquired resistance is unfortunately common. In order to combat this phenomenon, synthetic lethality is being investigated, making use of existing genetic fragilities within the cancer cell. This Perspective highlights exciting targets within synthetic lethality, (PARP, ATR, ATM, DNA-PKcs, WEE1, CDK12, RAD51, RAD52, and PD-1) and discusses the medicinal chemistry programs being used to interrogate them, the challenges these programs face, and what the future holds for this promising field.

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