SPECIAL NOTICE
Q -- Full Saturation Regulatory Study for a lead D3 Antagonist
- Notice Date
- 2/18/2022 2:06:57 PM
- Notice Type
- Special Notice
- NAICS
- 541380
— Testing Laboratories
- Contracting Office
- NATIONAL INSTITUTES OF HEALTH NIDA Bethesda MD 20892 USA
- ZIP Code
- 20892
- Response Due
- 2/25/2022 12:00:00 PM
- Point of Contact
- Michelle Cecilia
- E-Mail Address
-
michelle.cecilia@nih.gov
(michelle.cecilia@nih.gov)
- Description
- PRE-SOLICITATION NOTICE OF INTENT NON-COMPETITIVE Notice of Intent: 75N95022Q00121 INTRODUCTION PURSUANT TO FAR Subpart 5.2�Synopses of Proposed Contract Actions, THIS IS A PRE- SOLICITATION NOTICE OF A PROPOSED CONTRACT TO ACTION. THIS IS A PRE-SOLICITATION NON-COMPETITIVE NOTICE OF INTENT TO AWARD A CONTRACT OR PURCHASE ORDER WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION (INCLUDING BRAND-NAME). The National Institute on Drug Abuse (NIDA), Office of Acquisitions, Contracts Management ��Branch Blue, NCATS Section on behalf of the National Center for Advancing Translational Sciences intends to negotiate and award a contract for Full Saturation Regulatory Study for a lead D3 antagonist. NORTH AMERICAN INDUSTRY CLASSIFICATION SYSTEM (NAICS) CODE The intended procurement is classified under NAICS Code 541380: Medical-Laboratory Testing with a Size Standard of $16.5 million. REGULATORY AUTHORITY The resultant contract will include all applicable provisions and clauses of the Federal acquisition Regulation (FAR) in effect through the Federal Acquisition Circular 2022-02, dated January 14, 2022. STATUTORY AUTHORITY This acquisition is conducted under the authority of the Federal Acquisition Regulation (FAR) Part 13�Simplified Acquisition Procedures, Subpart 13.106-1 (b) (1), Soliciting from a single source. DESCRIPTION OF REQUIREMENT PROJECT DESCRIPTION The biogenic amine dopamine is an essential neurotransmitter in the brain and periphery. The cerebral dopaminergic system is implicated in a variety of physiological and pathophysiological processes. It comprises the regulation of motion, emotion and cognition. An imbalance in the dopaminergic neurotransmission and dopamine receptors underlies manifold neurological and psychiatric disorders. All drugs of abuse either directly or indirectly increase dopamine levels in the mesolimbic regions of the brain. The dopamine receptor subtype D3 is localized in the key neurocircuits that underlie motivation and cognition, and in contrast to D2R do not appear to play a major role in movement. Hence D3R has been proposed as a promising target for development of psychostimulant addiction and relapse pharmacotherapy. Also, seminal reports have shown increased D3R subtype in the basal ganglia in post-mortem brains of cocaine and methamphetamine overdose victims using PET studies thus further validating this approach. TRND at NCATS in collaboration with the investigators at NIDA has embarked on a journey to find novel D3R antagonists while displaying significant selectivity from the highly homologous D2 receptors. Working on the bitopic ligands identified by earlier investigations, the team has identified several lead chemotypes that display around a 500 fold selectivity over D2R in the binding assays. These lead molecules occupy an orthostatic binding site (OBS) at D3R and also connect to a secondary binding pocket (SBP), via a 4 carbon linker, responsible for achieving selectivity amongst the dopamine receptor subtypes. The lead molecules from different chemotype series, identified by the team are being considered for development. Towards a successful translation of these lead molecules and to study pharmacodynamics of these compounds, the team has proposed ex-vivo and in-vivo receptor occupancy studies in Sprague Dawley rats. In this study, we will determine the occupancy of a known D3 selective antagonist in D3 receptor rich regions of the brain. We will also be looking at the D2 receptor regions to evaluate the in-vivo selectivity of the antagonist. We plan to exploit the differential localization of D2 and D3 receptors in the rat striatum, Substantia Nigra, Ventral Tegmental Area, Olfactory tubercle, and Cerebellum lobes 9 and 10 in this study. While Substantia Nigra, VTA, OT and Cerebellar lobes 9 and 10 have been shown to be rich in D3R receptor expression, the receptor binding in the striatum can serve as the D2 rich control. Three different concentrations of D3 antagonist will be used in the study and a subsequent tail vein IV injection of 3H-PHNO will be performed after a set time to measure the occupancy of the D3 antagonist in the above-mentioned brain regions. Vehicle dosing will serve as a control for 3H-PHNO occupancy. General Requirements Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified, personnel, material, equipment, and facilities not otherwise provided by the Government as needed to perform the Specific Requirements below: 1) Na�ve rodents will be sourced for this study (n=20). 2) Single compound assay (4 groups, 5 rats per group): ��� i. Vehicle + 3 concentrations candidate compound 3) Animals will receive an IP or PO injection of vehicle/compound (dose route and concentrations to be finalized later). 4) After injection of vehicle/compound, animals will receive an IV injection of [3H]PHNO (dose to be finalized later). 5) At a single timepoint post-[3H]PHNO dosing, animals will be exsanguinated, and their brains will be harvested and fresh-frozen. 6) Brains will be sectioned coronally on a cryostat (10-20 ?m thickness) from anterior to posterior to include several regions of interest (typically prefrontal cortex, striatum, hippocampus, and cerebellum). 7) Sections will be apposed to a tritium-sensitive phosphoimaging plate alongside a tissue-equivalent microscale for expression of binding as fmol/mg tissue. 8) For quantification, regions of interest will be drawn on up to 3 areas. 9) Delivery of the ex vivo dose occupancy assay will consist of binding (fmol/mg tissue) of [3H]PHNO in the compound dosed tissues expressed as a percentage of total binding (vehicle dose) for each of the regions of interest. Statement of Work See Attached Period of Performance The period of performance is eight to ten weeks from date of award. CLOSING STATEMENT This synopsis is not a request for competitive proposals. However, interested parties may identify their interest and capability to respond to this notice. The respondents must submit clear and convincing evidence that their product is equivalent or superior to the product specified in this notice. The response shall include: the unit price, list price, shipping and handling costs, delivery days after contract award, delivery terms, prompt payment discount terms, F.O.B. Point (Destination or Origin), product or catalog number(s); product description; and any other information or factors that may be considered to determine the method of acquisition. The response must also indicate the country of manufacturer of components and country of assembly (not necessary for IT purchases). A determination by the Government not to compete this proposed contract based upon responses to this notice is solely within the discretion of the Government. The information received will normally be considered solely for the purposes of determining whether to proceed on a non- competitive basis or to conduct a competitive procurement. All responses must be received by February 25, 2022 at 3:00 PM Eastern Time and must reference number 75N95022Q00121. Responses must be submitted electronically to Michelle Cecilia, Contract Specialist, at michelle.cecilia@nih.gov, and must reference the solicitation number 75N95022Q00121, on your electronic request. FAX requests are not accepted. �All responsible sources may submit a capability statement, proposal, or quotation, which shall be considered by the agency.�
- Web Link
-
SAM.gov Permalink
(https://sam.gov/opp/ba9858c8284542aeae6c61cce2f044c9/view)
- Place of Performance
- Address: Bethesda, MD 20892, USA
- Zip Code: 20892
- Country: USA
- Zip Code: 20892
- Record
- SN06246859-F 20220220/220218230105 (samdaily.us)
- Source
-
SAM.gov Link to This Notice
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