Notice Number: NOT-NS-09-004

Key Dates
Release Date: December 29, 2008

Issued by
National Institute of Neurological Disorders and Stroke (NINDS), (http://www.ninds.nih.gov)

Purpose

The purpose of this notice is to announce that the NINDS is seeking experienced medicinal chemists to provide small molecule design support to investigators applying to the Research Funding Announcement NS-09-003, entitled; “Optimization of Small Molecule Probes for the Nervous System” (R21).  It is expected that medicinal chemistry planning will be included as part of a successful project proposal. Chemistry expertise will be needed to help design and evaluate small molecule analogues in support of structure-activity relationship studies and compound optimization.  NINDS, and other NIH Institutes participating in the Program (NIAAA, NIDA), acknowledge the importance of having medicinal chemistry input to the small molecule design and optimization required of this Program, and will therefore support funding allowance within proposals responding to RFA-NS-09-003 for attaining such expertise. Applicants to this Program that do not presently have access to such a resource will be able to choose from a listing that will be provided upon request by the Program Director, of qualified medicinal chemists that are willing to provide support as an active participant in the proposed studies.  As it is expected that compound acquisition in this Program will be substantially guided by external procurement using available cheminformatic tools the consultant services described in this notice will not require the provision of chemical synthesis support. 

Background

The service described in this notice is aimed at facilitating a partnership of medicinal chemists with investigators wishing to apply to the Research Funding Announcement (RFA-NS-09-003) entitled “Optimization of Small Molecule Probes for the Nervous System”, and issued by the National Institute of Neurological Disorders and Stroke (NINDS).  This Program aims to facilitate the discovery of new small molecule probes (pharmacological tools) for investigating biological function in the nervous system by providing funding for advanced medicinal chemistry and the biological testing of compounds.  Successful applications to the Program will have identified probe candidates via screening of small molecule collections, using in vitro assays of biological activity developed to interrogate these collections, and be able to relate structural features of these small molecules to their biological activity.  Project proposals will nominate small molecule probe candidates from distinct structural series for the further, iterative design and testing of analogues in structure-activity relationship studies, using in vitro assays of biological function adapted to the medium throughput screening requirements of this work.  These studies will have the goal of developing a small molecule probe possessing the attributes (eg: affinity, selectivity, activity) required for its use in future pharmacological studies proposed by the investigator. Applicants to the RFA-NS-09-003 Program are strongly encouraged to utilize publicly available cheminformatic capabilities for the acquisition of compounds, and semi-custom synthesis of analogues, which is required of these studies.  Applications to the Program will include biology and medicinal chemistry components, and it is expected that costs will be divided equally between the two components.  While Program applicants can propose the provision of both components required in an application it is anticipated that many investigators emerging from a high throughput small molecule screening effort will lack access to the medicinal chemistry expertise needed for effective follow-up in a molecular probe optimization effort.  For this reason, NINDS and other participating NIH Institutes will make available to applicants a list of medicinal chemists that will be available to participate in project proposals by contributing the required chemistry component.

Chemists participating in the service are expected to participate in the grant planning as regards its chemistry component, and fulfill chemistry activities as required by the Program in the event that the proposal is funded. These activities will include the following:

• Identification of small molecule compound “scaffolds” suitable for extended medicinal chemistry optimization effort, selected using validated data originating from biological screens of small molecule compound libraries.
• Design of small molecule compound structure-activity relationship (SAR) studies aimed at the exploring the contributions of structural elements intrinsic to a small molecule scaffold structure that are necessary for it to have the biological attributes required in a pharmacological tool. 
• The analysis of biological test results measuring the required biological attributes, and lead to the proposal of analogues that enhance (or eliminate) desired (or undesired) attributes of the small molecules that are the subject of the SAR studies
• Cheminformatic searching for scaffold-like or small molecule analogue structures that fit the scope of the proposed SAR planning.
• Identification of source, availability and purchase information for the acquisition of small molecule analogues used in studies proposed by the principal investigator. 
• Support to the preparation of publications describing the results of the proposed SAR investigation and analogue design and testing effort, and/or results of pharmacological studies describing the activity of the small molecules resulting from this design effort.
• Support for patenting of scaffolds and small molecule analogues identified in the course of the proposed studies. 

Medicinal Chemists applying to provide this service will be pre-qualified by Institute Program staff before acceptance to the listing, using criteria which include the following:

• Advanced degree (M.S., Ph.D.) in chemistry
•  Experience in small molecule medicinal chemistry.  To include:
• Prior work designing small molecule structure-activity relationship (SAR) studies aimed at the development of small molecules that are useful in proof-of-principle pharmacology studies linking biological mechanisms to a disease involvement, and as therapeutic candidates.
• Experience in the synthesis of small molecule compounds, demonstrating expert knowledge in the application of chemical synthetic routes and strategies.
• Familiarity with small molecule design and synthesis using biased array approaches.
• Experience in the development of SAR knowledge beginning from compounds identified via biological activity screening of small molecule collections.         
• Track record of publication of small molecule SAR studies in scholarly journals.
• Record of patenting as inventor small molecules proposed as, or resulting from, the design and execution of SAR planning aimed at the development of small molecule pharmacological tools.
• Familiarity in the use of cheminformatic tools as applied to the search, selection and acquisition of small molecules and small molecule analogues that would be employed in a SAR design effort.

Please Note the Following:

• Payment for chemistry services is contingent upon funding of the grant proposal, and will be administered by the Principal Investigator’s institution.
• Chemists participating in the medicinal chemistry support service can participate in more than one proposal to the grant Funding Program. 
• NINDS, and the other participating NIH Institutes, will not assume responsibility for service provider oversight or performance.
• All parties participating in studies funded in response to RFA-NS-09-003, including any medicinal chemists participating in the compound design, will be given adequate consideration in determining inventorship and participation in publications.
• A detailed description of the goals of the Optimization of Small Molecule Probes for the Nervous System (R21) Program can be found in the funding announcement for the Program: http://grants.nih.gov/grants/guide/rfa-files/RFA-NS-09-003.html.   

How to Apply

Applicants to the medicinal chemistry consultant listing service should send their curriculum vitae, list of references, and proposed consulting budget to Dr. Mark Scheideler at the email address listed below.  The closing date for applications is January 30, 2009.  Applications will be reviewed as they are received.  Applications received after the closing date will be reviewed subsequent to this date on a need basis.

For further information regarding eligibility for the medicinal chemistry consultant listing service, specific requirements of the work, and process for applying to the listing, please contact:

Mark Scheideler, Ph.D.
Senior Scientific Officer, NINDS
Telephone: 301-496.1779
Email address: scheidelerm@ninds.nih.gov