Identification of the Clinical Candidate (), a Highly Potent and Brain Penetrant BRAF Inhibitor for the Treatment of Cancer.

Mutant BRAF is one of the most common oncogenic drivers in metastatic melanoma. While first generation BRAF inhibitors are capable of controlling tumors systemically, they are unable to adequately treat tumors that have metastasized to the brain due to insufficient penetration across the blood-brain barrier (BBB). Through a combination of structure-based drug design (SBDD) and the optimization of physiochemical properties to enhance BBB penetration, we herein report the discovery of the brain-penetrant BRAF inhibitor () In mice studies, proved to be highly brain-penetrant and was able to drive regressions of A375 BRAF tumors implanted both subcutaneously and intracranially.

SPACEWALK: A Remote Participation Study of ALK Resistance Leveraging Plasma Cell-Free DNA Genotyping.

Introduction: Remote consent and enrollment offer a unique opportunity to provide rare cancer populations with access to clinical research. The genomic analysis of plasma cell-free DNA (cfDNA) permits remote characterization of the cancer genome. We hypothesized we could leverage these approaches to remotely study drug resistance in patients with metastatic -positive NSCLC.

Property-Guided Synthesis of Aza-Tricyclic Indolines: Development of Gold Catalysis En Route.

Antibiotic resistance is a worldwide public health threat that needs to be addressed by improved antibiotic stewardship and continuing development of new chemical entities to treat resistant bacterial infections. Compounds that work alongside known antibiotics as combination therapies offer an efficient and sustainable approach to counteract antibiotic resistance in bacteria. Guided by property-based analysis, a series of aza-tricyclic indolines (ATIs) were synthesized to optimize their physiochemical properties as novel combination therapies with β-lactams to treat methicillin-resistant (MRSA) infections.

Telehealth for patients with Parkinson's disease: delivering efficient and sustainable long-term care.

Objectives: We set out to demonstrate the benefits of providing long-term care via telehealth for patients with Parkinson's disease living in continuous care facilities.

Methods: A cohort of 16 patients with Parkinson's disease residing at one of 2 locations of a multi-facility continuous care retirement organization were seen virtually in follow-up over a 3-year period by Telehealth Services at a large, academic, tertiary care hospital in southeastern Pennsylvania. The data collected during that period, studied retrospectively, included demographic information, number of telehealth visits, and UPDRS scores obtained at each visit.

Spectrum and potential pathogenesis of reversible posterior leukoencephalopathy syndrome.

Background: Controversy still exists over the etiology and pathophysiology of reversible posterior leukoencephalopathy syndrome (RPLS). This large single-center case series aims to describe the clinical and imaging features of RPLS in an attempt to deduce the etiology of the disorder and the mechanisms of brain injury.

Methods: A retrospective chart and imaging review was conducted on 59 cases of RPLS in 55 patients.