title: A review on PARP1 inhibitors: Pharmacophore modeling, virtual and biological screening studies to identify novel PARP1 inhibitors.
abstract: A tremendous research on Poly (ADP-ribose) polymerase (PARP) pertaining to cancer and ischemia is in very rapid progress. PARP's are a specific class of enzymes that repairs the damaged DNA. Recent findings suggest also that PARP-1 is the most abundantly expressed nuclear enzyme which involves in various therapeutic areas like inflammation, stroke, cardiac ischemia, cancer and diabetes. The current review describes the overview on clinical candidates of PARP1 and its current status in clinical trials. This paper also covers identification of potent PARP1 inhibitors using structure and ligand based pharmacophore models. Finally 36 potential hits were identified from the virtual screening of pharmacophore models and screened for PARP1 activity. 15 actives were identified as potent PARP1 inhibitors and further optimization of these analogues are in progress.
authors.forename: Sardar Shamshair
authors.initials: SS
authors.lastname: Singh
authors.forename: Jagarlapudi A R P
authors.initials: JA
authors.lastname: Sarma
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Narasu
authors.forename: Raveendra
authors.initials: R
authors.lastname: Dayam
authors.forename: Shili
authors.initials: S
authors.lastname: Xu
authors.affiliation: GVK Biosciences Pvt. Ltd., Plot No 79, IDA, Mallapur, Hyderabad 500076, Andhra Pradesh, India. shamshairsingh@gmail.com.
authors.forename: Nouri
authors.initials: N
authors.lastname: Neamati
mesh_terms: D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D062105:Molecular Docking Simulation; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases