Justin M. Wright

Halo-Enediynes: Probing the Electronic and Stereoelectronic Contributions to the Bergman Cycloaromatization

Efficient routes to three classes of 10-membered oxa-enediynes are presented. The electronic and stereoelectronic contributions to half-lives are supported by density functional theory calculations. One member of this class cyclizes to give an isochroman which binds to and degrades the aryl hydrocarbon receptor (AhR).

Stereoselective access to substituted enediyne building blocks

Abstract Intermolecular coupling-elimination of disubstituted propargyl bromides gives rise to differentiallysubstituted 3-hexen-1,5-diynes with E:Z selectivity as high as 100:1. Application of the methodology in the synthesis of key nanomaterial building blocks is demonstrated.

Chemical synthesis of hormone receptor probes: high affinity photoactivated enediyne-estrogens

Abstract A family of enediyne-estrogens has been prepared, and evaluated for affinity to hER. The optimal ligand has nM affinity, and undergoes photoBergman cycloaromatization.

Target directed enediyne prodrugs: hER and AhR degradation by a synthetic oxo-enediyne

Abstract An efficient route to oxo-enediynes is presented. A simple oxo-enediyne has been synthesized, which cyclizes to give an isochroman. The agent shows cytotoxicity for ER rich breast cancer cells and a model for its mode of action is proposed.

Stereochemical control in the metallohalocarbenoid route to linear enediynes

Abstract Methods for the stereoselective preparation and unmasking of disubstituted Z enediynes are reported. The origins of the unprecedented stereoselectivity of the process are uncovered.

Harnessing the Digital Exhaust: Incorporating Wellness into the Pharma Model

The increasing availability of devices capable of tracking biomarkers presents major opportunities in contemporary healthcare. Herein we advocate a new role for the pharmaceutical industry to capitalize on these opportunities and, in doing so, incorporate wellness and patient engagement programs into their standard business models. Medical-grade decision-making using diagnostic, prognostic, and monitoring biomarkers will require coordinated approaches between the pharmaceutical and technology industries and the careful design of longitudinal clinical studies to validate their efficacy. These studies will also require data capture, archiving, curating, and sharing on a previously unprecedented scale, and raise additional concerns with regard to data security and ownership. Concurrently, systems-based approaches to the capture and interpretation of a new class of digital biomarkers are emerging, and they hold promise for heightened levels of patient engagement and remote sensing. Collectively, if these new opportunities are approached within the context of the patient-provider ecosystem, major repositioning of the pharmaceutical industry may be possible in the near future.

Can composite digital monitoring biomarkers come of age? A framework for utilization

Introduction The application of digital monitoring biomarkers in health, wellness and disease management is reviewed. Harnessing the near limitless capacity of these approaches in the managed healthcare continuum will benefit from a systems-based architecture which presents data quality, quantity, and ease of capture within a decision-making dashboard. Methods A framework was developed which stratifies key components and advances the concept of contextualized biomarkers. The framework codifies how direct, indirect, composite, and contextualized composite data can drive innovation for the application of digital biomarkers in healthcare. Results The de novo framework implies consideration of physiological, behavioral, and environmental factors in the context of biomarker capture and analysis. Application in disease and wellness is highlighted, and incorporation in clinical feedback loops and closed-loop systems is illustrated. Conclusions The study of contextualized biomarkers has the potential to offer rich and insightful data for clinical decision making. Moreover, advancement of the field will benefit from innovation at the intersection of medicine, engineering, and science. Technological developments in this dynamic field will thus fuel its logical evolution guided by inputs from patients, physicians, healthcare providers, end-payors, actuarists, medical device manufacturers, and drug companies.