{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kellett T"],"funding":["NCI NIH HHS"],"pagination":["394-401"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10872402"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["28(8)"],"pubmed_abstract":["PARP1/2 inhibitors (PARPi) are effective clinically used drugs for the treatment of cancers with BRCA deficiencies. PARPi have had limited success and applicability beyond BRCA deficient cancers, and their effect is diminished by resistance mechanisms. The recent discovery of Histone PARylation Factor (HPF1) and the role it plays in the PARylation reaction by forming a shared active site with PARP1 raises the possibility that novel inhibitors that target the PARP1-HPF1 complex can be identified. Herein we describe a simple and cost-effective high-throughput screening (HTS) method aimed at discovering inhibitors of the PARP1-HPF1 complex. Upon HTS validation, we first applied this method to screen a small PARP-focused library of compounds and then scale up our approach using robotic automat"],"journal":["SLAS discovery : advancing life sciences R & D"],"pubmed_title":["HTS discovery of PARP1-HPF1 complex inhibitors in cancer."],"pmcid":["PMC10872402"],"funding_grant_id":["P30 CA046934","R01 CA218255","P30 CA008748","R01 CA251361"],"pubmed_authors":["Zhou Q","Rudolph J","LaBarbera DV","Esquer H","Kellett T","Stojanovic P","Noor R","Luger K","Sala R"],"additional_accession":[]},"is_claimable":false,"name":"HTS discovery of PARP1-HPF1 complex inhibitors in cancer.","description":"PARP1/2 inhibitors (PARPi) are effective clinically used drugs for the treatment of cancers with BRCA deficiencies. PARPi have had limited success and applicability beyond BRCA deficient cancers, and their effect is diminished by resistance mechanisms. The recent discovery of Histone PARylation Factor (HPF1) and the role it plays in the PARylation reaction by forming a shared active site with PARP1 raises the possibility that novel inhibitors that target the PARP1-HPF1 complex can be identified. Herein we describe a simple and cost-effective high-throughput screening (HTS) method aimed at discovering inhibitors of the PARP1-HPF1 complex. Upon HTS validation, we first applied this method to screen a small PARP-focused library of compounds and then scale up our approach using robotic automat","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Dec","modification":"2025-04-05T09:07:27.599Z","creation":"2025-04-05T09:07:27.599Z"},"accession":"S-EPMC10872402","cross_references":{"pubmed":["37844763"],"doi":["10.1016/j.slasd.2023.10.003"]}}