HEAL: New Chemical Structures for Pain, Addiction and Overdose Targets

National Center For Advancing Translational Sciences

Investigators

Linked publications & trials

Abstract

The past year has seen the buildout of the infrastructure necessary to achieve the overall goals of the program across several key areas: Personnel, Hardware, Information Technology (IT), Informatics, Logistics and Facilities. 1. Personnel: The program has started initially by taking a collection of existing NCATS personnel across a variety of disciplines ranging from chemistry, engineering, information technology, informatics and biology and having them work in a team environment to break the challenge down into manageable parts. Over the course of the year we have moved several existing staff members into exclusively ASPIRE functions to build out the core team. We have also hired a permanent lead of the initiative and by the end of the year will have several key chemistry and automation positions filled. These are incredibly difficult positions to recruit capable candidates for given the multidisciplinary requirements of the program, so we are pleased with the progress of filling out several core members. 2. Hardware: Several key pieces of hardware have been acquired in the past year to enhance our overall chemistry capabilities with an eye towards automation and eventually autonomy. A key factor for any piece of hardware purchased is that it must have an accessible API and the instrument must be capable of being integrated within a larger overall platform. Key equipment acquired has given us the capability of performing programmatic and automated synthetic chemical reactions, platforms to perform reaction screening evaluation, flow and batch synthesis with a focus on the ability to scale reaction output up, autonomous mobile robotic platforms and others. The overall focus has been to increase our automated chemistry capabilities via commercially available products and custom instrumentation projects. 3. Information Technology: A key area of focus for the past year was the establishment of an overall IT strategy that considers the distributed nature of the program and the requirement of secure interconnected systems acting in a synchronized fashion. A key requirement is the integration of informatics platform to communicate and control instrumentation allowing for programmatic execution of experiments with the results being fed back to the overall system controller to help initiate the next round of experiments. A beta system has been deployed to connect existing robotic platforms with an informatics driven controller and we have begun testing of this model. 4. Informatics: Aside from the afore-mentioned informatics driven experimentation a key area of focus has been on retrosynthetic analysis, both via commercial software and internally developed applications. Time was spent with chemists and informatics to evaluate commercially available software in this space and although it was determined it was not quite ready to assist with traditional medicinal chemistry projects, it would be well suited to integrate within an automated platform to help drive novel synthetic reactions. Work has also been done to extract information from our existing electronic laboratory notebook (ELN) which contains tens of thousands of reactions performed at NCATS over the years to create a reaction database that can is accessible via an API to perform reaction analytics to help facilitate robotic driven synthesis. There is currently a beta application use with a project being initiated to deploy this as a production system in the IT provided cloud environment. 5. Logistics and Facilities: We have finally gotten preliminary access to additional space which will be required to build out the ASPIRE platform. In the meantime, we have identified existing space that has been setup for use as the initial ASPIRE lab for prototyping and testing of new equipment and systems. The overall progress for the year has been to advance the program in several different directions, primarily in chemistry, IT and informatics and to also begin to demonstrate how they will be integrated in an automated fashion eventually at a large scale.