Statement_of_Work.doc

Statement of Work

Project Title:

ADME, Toxicity, and Transporter Assays for Lead Compound Background

The National Institutes of Health (NIH) is the nation’s leading medical research agency and the primary Federal agency whose mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability, conducting, supporting and making medical discoveries that improve people’s health and save lives.

The National Center for Advancing Translational Sciences (NCATS) is a translational science center that prides itself on its tremendously productive pipeline and is innovative in a number of ways. First, our quantitative high throughput screening (qHTS) paradigm, which tests all compounds at multiple concentrations in the primary screen, is unique. Second, the NCATS is distinctive in its focus on collaboration with outside investigators to produce high-quality chemical probes to define and assess new biology. This focus is reflected in our unprecedented Outreach program, which reaches hundreds of potential new investigators every year, and accounts for much of the new science being done at the NCATS. Third, the NCATS is uniquely focused on new technologies and paradigms to improve the process of translational science, typified by qHTS, our informatics platform, our utilization of structural biology to accelerate probe development, development of new synthetic and analytical chemistry paradigms. Ultimately, NCATS brings together a diverse range of scientists, including medicinal chemists, biologists, toxicologists, and engineers, in order to ultimately translate basic science into real products and services that help improve people’s lives. Included in this process is the development of unique biological discoveries into potential pharmaceuticals which can greatly assist patients ADME (Absorption, Distribution, Metabolism, & Excretion) assesses the effects of a drug or drug-like compound against a variety of assays, designed to analyze how a drug is distributed and processed within the human body. Early ADME assays are critical to determine the effect and potential side effects of drug-like compounds in the human body. A drug that is poorly absorbed and distributed or a drug that is too rapidly excreted will be of limited utility, no matter how effective it is in vitro. Likewise, a drug that is metabolized too quickly may result in a compound that is ineffective towards its desired target. Metabolite profiling gives insight into the potential degradation pathways. Toxicity is related to ADME, in that a drug that is too toxic may not be administered to humans, even if it is effective.

In addition, there are several proteins that act as drug transporters within the human body, including OATP1A2, OAT1, OCT1, OCT3, and MATE1. These proteins act to transport small molecules across a variety of membranes in several different organ systems, including the intestines, liver, kidneys and the blood-brain barrier. Recently these transporters have come to receive heightened scrutiny in developing new pharmaceuticals, as inhibition of these transporters can result in unanticipated drug-drug interactions.

Currently, NCATS is developing Lead Compound as a potential treatment for major depressive disorder. In order to safely advance Lead Compound towards human trials and Investigational New Drug, it is critical that required ADME and Transporter assays be performed, Statement of Objective

The objective of this acquisition is to acquire screening of Lead Compound against a panel of ADME and toxicity studies and against panel of transporter proteins, including BSEP, BCRP, OATP1B1, OATP1b3, OAT1, OAT3, OCT1, OCT2, MATE1, and MATE2-K.

Deliverables / Reporting Requirements:

NCATS will provide up to 100 mg of Lead Compound for assessment upon completion of the purchase order

Contractor will provide a full IND enabling report for the required assays Period of Performance

1. Period of performance is within 12 weeks compound receipt Section 508 Electronic and Information Technology Standards

N/A

CONTRACTING OFFICER'S REPRESENTATIVE (COR)

The following Contracting Officer's Representative (COR) will represent the Government for the purpose of this contract:

TBD at time of award

Mandatory Criteria (Requirements)

1) Contractor will be able to provide all services within 12 weeks of compound receipt.

2) Contractor will be able to provide all services listed below.

a. BSEP inhibition assay. An IC50 for Lead Compound will be determined against the BSEP transporter

b. BCRP Assay. An IC50 for Lead Compound will be determined.

c. SLC Transporter Inhibition assays. An IC50 for Lead Compound will be determined against each of the below transporter proteins

i. OATP1B1

ii. OATP1B3

iii. OAT1

iv. OAT3

v. OCT1

vi. OCT2

vii. MATE1

viii. MATE2-K

3) Appropriate controls for each of these assays will be utilized

4) Contractor will have previous experience with all of these assays

5) Company must provide a professional and comprehensive report with all the relevant results from the service rendered.

6) Contractor will be based in the United States

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