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FBO DAILY - FEDBIZOPPS ISSUE OF JULY 24, 2015 FBO #4991
SOURCES SOUGHT

B -- Functional Evaluation of Compounds for Opioid Receptor Efficacy

Notice Date

7/22/2015
 

Notice Type

Sources Sought
 

NAICS

541690 — Other Scientific and Technical Consulting Services
 

Contracting Office

Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse, Station Support/Simplified Acquisitions, 31 Center Drive, Room 1B59, Bethesda, Maryland, 20892
 

ZIP Code

20892
 

Solicitation Number

HHS-NIH-NIDA-SSSA-SBSS-15-646
 

Archive Date

8/13/2015
 

Point of Contact

Farrin Stanton, , ,
 

E-Mail Address

farrin.stanton@nih.gov, farrin.stanton@nih.gov
(farrin.stanton@nih.gov, farrin.stanton@nih.gov)
 

Small Business Set-Aside

N/A
 

Description

This is a Small Business Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding: (1) the availability and capability of qualified small business sources, (2) whether they are small businesses; HUBZone small businesses, service-disabled, veteran-owned small businesses; 8(a) small businesses; veteran-owned small businesses; woman-owned small businesses; or small disadvantaged businesses; and (3) their size classification relative to the North American Industry Classification System (NAICS) code for the proposed acquisition. Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible. This notice is issued to help determine the availability of qualified companies technically capable of meeting the Government requirement and to determine the method of acquisition. It is not to be construed as a commitment by the Government to issue a solicitation or ultimately award a contract. Responses will not be considered as proposals or quotes. No award will be made as a result of this notice. The Government will NOT be responsible for any costs incurred by the respondents to this notice. The notice is strictly for research and information purposes only. The information requested will assist the Government in determining the appropriate acquisition method, including whether a small business social-economic set-aside, competitive or non-competitive method is possible, and to determine the availability of qualified companies technically capable of meeting the Government's requirement. ALL organizations with the capability and availability to perform the requirement under the applicable NAICS code are invited to submit a response to this notice. NORTH AMERICAN CLASSIFICATION SYSTEM (NAICS) CODE 541690 Other Scientific and Technical Consulting Services The mission of the Intramural Research Program (IRP) of the National Institute on Drug Abuse is to conduct state-of-the-art research on basic mechanisms that underlie drug abuse and addiction, and to develop new methods for the treatment of drug abuse and addiction. Research is supported at the molecular, genetic, cellular, animal, and clinical levels and is conceptually integrated, highly innovative, and focused on major problems in the field. The long-term goal of the research is to better understand the biological and behavioral factors contributing to initiation, maintenance, and elimination of drug abuse and addiction (and associated diseases), and to translate this knowledge into improved strategies for preventing, treating, and reducing the negative consequences for the individual and for society caused by drug abuse and addiction. The Drug Design and Synthesis Section (DDSS) major research direction is the elucidation of the structure and function of neurotransmitter systems in the mammalian central nervous system (CNS) in normal, drug-altered, and pathological states and the molecular mechanism of action of CNS active drugs. Organic/medicinal chemistry is the foundation of the multidisciplinary approach utilized in these studies that requires the rational design and chemical synthesis of novel agonists, antagonists, imaging agents, affinity ligands, and other drugs for particular applications. Our principal focus is the application of these techniques to study the mechanism of action of abused drugs and the development of medications for the treatment and prevention of drug abuse. Purpose and Objectives: The DDSS needs the services of a Contractor to assay novel compounds that have been synthesized in house for specific opioid receptors. Project Requirements: Specifically, the vendor will provide the following services: 1) Examine submitted compounds for their agonist or antagonist activity at three opioid receptors, mu, delta and kappa. a. Pure compounds (approx. 5 mg) will be supplied by the NIDA IRP’s DDSS as coded compounds such that analysis is blinded. b. Compounds will have been previously pre-screened for binding affinity and only compounds with an affinity of ≥ 100nM will be supplied. 2) The submitted compounds will be evaluated for opioid efficacy using the [ 35 S]GTPγS (guanosine-5’-O-(3-thio)triphosphate) assay as follows: a. Membrane homogenates from cloned cell lines expressing mu, delta or kappa receptors will be used. Membrane proteins (10 g) are incubated for 1 h at 25ºC in buffer (50mM Tris pH 7.4, 100mM NaCl, 5mM MgCl 2, 1mM EDTA] with 0.1nM [ 35 S]GTPγS, 30 μM GDP (guanosine 5’-diphosphate) and test compound. An internal standard at 10µM (DAMGO for Mu, SNC80 for delta, U69593 for kappa) is used to define maximal activation. The assays are terminated by rapid filtration through GF/C filters, washed and [ 35 S]GTPγS bound determined by scintillation counting. 3) All experiments are run in duplicate and repeated a minimum of three-times. 4) Analysis: Compounds will be evaluated at all three opioid receptors as follows: a. Agonist activity: An initial screen will be performed at 10 M drug concentration. Compounds showing agonist activity will be then studied across a range of 8 doses to determine if they are full or partial agonists and their potency, compared to standard accepted full agonists at each receptor – Mu (DAMGO), Delta, (SNC80) and kappa (U69593). b. Compounds showing no agonism (<10% of standard) will be examined as antagonists. Concentration-response curves for the standard agonists will be performed over 8 concentrations in the presence or absence of test compound added at10-times its receptor binding affinity. Antagonist activity will be compared to standard known antagonists – Mu (CTOP), Delta (Naltrindole) and kappa (nor-Binaltorphimine) as well as naloxone as a standard non-selective antagonist. c. Concentration response curves will be analyzed using GraphPad Prism® ( La Jolla, CA) to provide potency values (EC50) for each compound and maximal stimulation compared to the full standard agonists at each receptor as stated above. Compounds showing less than 90% of the effect of the appropriate full agonist will be designated as partial agonists. d. For antagonists the ability to shift the concentration-effect curves for agonists will be analyzed to provide antagonist affinity constants (Ke values), that will be compared to the standard known antagonists listed above plus naloxone as a standard non-selective antagonist. 5) Productivity: It is estimated that 75 assays can be run per month. This equates to full concentration responses curves, repeated three times, for 25 compounds at a single receptor or 8 compounds at all three receptors. Only half as many antagonist compounds can be evaluated. This is because of the need for two concentration-response curves for each antagonist (agonist curves with and without antagonist). 6) Data Submission: the Contactor will perform analyses of data to provide Potency (EC50) and Maximal Effect (% of standard agonist) and/or Antagonist Dissociation Constants (Ke) and this data submitted to the NIDA IRP. The data will be in table form with statistical analysis, appropriate for publication in high impact Medicinal Chemistry/Organic Chemistry journals. If requested graphical representations of the data will be provided 7) Questions: the Contractor will be available to answer any queries that arise from material submitted to DDSS, or questions from reviewers or publishers of scientific journals Period of Performance: The base period of performance shall be 1 year from notice of award. CAPABILITY STATEMENT INFORMATION SOUGHT Respondents must provide, as part of their responses, clear and convincing documentation of their capability of providing the item(s) specified in this notice. Contractors that believe they possess the ability to provide the required must submit specific documentation of their ability to meet each of the project requirements to the Contract Specialist. Contractors must provide their Company Name, DUNS number, Physical Address, and Point of Contact Information. Interested organizations are required to identify their type of business, applicable North American Industry Classification System Code, and size standards in accordance with the Small Business Administration. The government requests that no proprietary or confidential business data be submitted in a response to this notice. However, responses that indicate the information therein is proprietary will be properly safeguarded for Government use only. Capability statements must include the name and telephone number of a point of contact having authority and knowledge to discuss responses with Government representatives. Capability statements in response to this market survey that do not provide sufficient information for evaluation will be considered non-responsive. When submitting this information, please reference the solicitation notice number. All capability statements sent in response to this Sources Sought Notice must be submitted electronically (via email) to Farrin Stanton, Contract Specialist, at Farrin.Stanton@nih.gov in MS Word format by or before the closing date of this announcement. All responses must be received by the specified due date and time in order to be considered. The response must be received on or before July 29, 2015 11:00am, eastern time. CONCLUDING STATEMENTS Note: This notice does not obligate the Government to award a contract or otherwise pay for the information provided in the response. No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization's qualifications to perform the work. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After review of the responses received, pre-solicitation and solicitation notices may be published in Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation. The solicitation release date is pending. The Government intends to negotiate a fixed-price purchase order. Confidentiality. No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).
 

Web Link

FBO.gov Permalink
(https://www.fbo.gov/spg/HHS/NIH/NIDA-2/HHS-NIH-NIDA-SSSA-SBSS-15-646/listing.html)
 

Place of Performance

Address: 31 Center Drive, Bethesda, Maryland, 20879, United States

Zip Code: 20879
 

Record

SN03806877-W 20150724/150723000302-5b666a36151ea870ddca88c234229aa5 (fbodaily.com)
 

Source

FedBizOpps Link to This Notice
(may not be valid after Archive Date)

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