Cell-active Small Molecule Inhibitors of the DNA-damage Repair Enzyme Poly(ADP-ribose) Glycohydrolase (PARG) : Discovery and Optimization of Orally Bioavailable Quinazolinedione Sulfonamides

DNA damage repair enzymes are promising targets in the development of new therapeutic agents for a wide range of cancers and potentially other diseases. The enzyme poly­(ADP-ribose) glycohydrolase (PARG) plays a pivotal role in the regulation of DNA repair mechanisms; however, the lack of potent drug-like inhibitors for use in cellular and in vivo models has limited the investigation of its potential as a novel therapeutic target. Using the crystal structure of human PARG in complex with the weakly active and cytotoxic anthraquinone <b>8a</b>, novel quinazolinedione sulfonamides PARG inhibitors have been identified by means of structure-based virtual screening and library design. 1-Oxetan-3-ylmethyl derivatives <b>33d</b> and <b>35d</b> were selected for preliminary investigations in vivo. X-ray crystal structures help rationalize the observed structure–activity relationships of these novel inhibitors

Synthesis of nitrogen-containing heterocycles using novel aza-Wittig methodology

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Short-term Repeat Magnetic Resonance Imaging Scans in Suspected Early Axial Spondyloarthritis Are Clinically Relevant Only in HLA-B27–positive Male Subjects

Objective; Our study investigated the natural history of magnetic resonance imaging (MRI)–determined bone marrow edema over a 12-week period in individuals with suspected axial spondyloarthritis. Methods; There were 109 MRI scans performed on 30 patients who fulfilled the Assessment of Spondyloarthritis international Society inflammatory back pain criteria at baseline and at 4, 8, and 12 weeks. Results; There were 29 patients who completed the study. Only 4 (14%) patients changed from MRI-negative to MRI-positive (all HLA-B27–positive, OR 2.74). Three of 7 (43%) male HLA-B27–positive patients, 1 of 8 (12.5%) HLA-B27–positive female patients, and no HLA-B27–negative patients changed from MRI- negative to -positive. Conclusion; Repeat MRI scans within a 12-week period should be considered in HLA-B27–positive males

ORCID Peer Review Week 2017 Webinar: ORCID Peer Review Integration (Aries Systems Corporation)

Presentation on Aries Systems Corporations' ORCID peer review integration for the ORCID Peer Review Week 2017 webinar on September 14, 2017

ORCID Peer Review Week 2017 Webinar: ORCID Peer Review Integration (Aries Systems Corporation)

Presentation on Aries Systems Corporations' ORCID peer review integration for the ORCID Peer Review Week 2017 webinar on September 14, 2017