About this Research Topic
Deficiency in DNA damage repair results in an increased risk of oncogenic transformation and genome instability. In the meantime, such a deficiency could be exploited for the treatment of different tumors through inducing excessive genome instability and catastrophic DNA damage. A higher demand of DNA repair components is required for the continuous DNA replication in cancer cells. On the account of incomplete DNA repair repertoire and oncogenic loss of some DNA repair effectors (e.g. BRCA), diverse cancer cells are addicted to some DNA repair pathways, such as Poly (ADP-ribose) polymerase (PARP)-related single-strand break repair pathway. Recently, there have been many indications that a broader population of cancer patients could benefit from PARP inhibition-based therapy far beyond those with germline BRCA1/2 mutated tumors.
PARPs are a family of enzymes that catalyze the transfer of ADP-ribose from nicotinamide adenine dinucleotide (NAD+) onto acceptor proteins. PARP-1, among this family, is the most widely investigated member due to its critical role as a DNA repair enzyme in the base excision repair pathway, and its association with a variety of cellular functions such as regulation of cell death, transcriptional modulation of gene expression, and inflammation. Subsequently, therapeutic strategies based on the inhibition of PARP-1, in the current medical era, emerged as promising drug targets for targeted cancer therapy with many clinical benefits in human malignancies treatment. Significant advances have been achieved in PARP-1 inhibitors, specifically, the FDA-approval of four PARPIs; Olaparib, Rucaparib, Niraparib and Talazoparib.
This Research Topic deals with manuscripts concerning with discovery and development of promising and effective PARPIs as new cancer therapies, through updating and modifying drug leads from the point of view of medicinal chemistry and drug design.
• Computer-Aided Drug Design of Novel PARP Inhibitors
• Synthesis and Biological Evaluation of Novel Small Molecules As PARP Inhibitors
• Natural and Semisynthetic Products as Potential PARP Inhibitors
• Drug Repositioning
Keywords: PARP inhibitors, drug design, organic synthesis, anticancer gents, drug repositioning
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