DOI: 10.5176/978-981-08-8119-1_BioTech2011_11
Authors: Prenitha Mercy and Dr. C. Sudandiradoss
Abstract:
Poly ADP-ribose polymerase (PARP) facilitates DNA single-strand break–base excision repair to maintain genomic stability. Inhibition or loss of PARP activity leads to a recombinogenic phenotype characterized by increased sister chromatid exchange. Deficiency in homologous recombination (HR) owing to loss of BRCA1 or BRCA2 is associated with hereditary cancers of the breast, ovary, pancreas and prostate. In this work, we have taken the 5 PARP inhibitors namely iniparib, olaparib, Veliparib (ABT-888), AG014699 and 3-aminobenzamide which are currently under clinical trials and not yet approved
for therapeutic purpose. Also, we computationally docked these molecules against 17 types of PARP enzyme molecules to identify the best promising future candidate for treating the BRCA associated
cancers. Out of 5 PARP inhibitors, AG014699 showed the best binding affinity and structural stability towards the PARP enzyme molecules. Apart from PARP 1 (PDB ID: 1uk0), PARP2 (PDB ID: 1gs0),
PARP3 (PDB ID: 2pa9), PARP10 (PDB ID: 2dhx), PARP12 (PDB ID: 2pqf) which has the three dimensional (3D) structures, we obtained the remaining structures through homology modelling.
Hence, we report AG014699 could be the promising and potential PARP inhibitors for treating the BRCA associated cancers.
Keywords: PARP inhibitor, breast cancer,chemotherapy, computation, PTEN- defective, tumours
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