B. AP SOW_Statement_of_Work_f.pdf

Version 11-30-2016-1 FAR Part 11—Describing Agency Needs

STATEMENT OF WORK (SERVICES)

(SOW)

GENERAL INFORMATION

Determining Kinases Inhibition by Anti-malarial Compounds

NCATS requires contractor results of profiling malaria compounds against a panel of human kinases for 4500 data points at one concentration and 300 IC50 curves.

Plasmodium falciparum malaria remains a major threat to the public health, especially in tropical and subtropical areas of the world’s poorest countries. The life cycle of Plasmodium falciparum malaria comprises an exogenous sexual phase with multiplication in certain mosquitoes corresponding to the vector of the disease and an endogenous asexual phase with multiplication in the human host. During a blood meal, a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host.

After several asexual cycles in the blood following the hepatic cycle, some merozoites can differentiate into sexual forms known as macro (female) or micro (male) gametocytes. This production of gametocytes from asexual parasites is named gametocytogenesis. Ingestion of these gametocytes by the invertebrate host allows for the following gametocytogenesis process and the continuation of the parasite cycle.

Although the malaria illness is caused by the asexual blood stages, the presence of gametocytes is directly responsible for the infection of the anopheline vector, thus perpetuating the plasmodial cycle.

Thus, identifying drugs which can kill gametocytes is an essential strategy in antimalarial drug development.

Recently we have identified a series of (quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-ones with gametocytes killing activity. Since similar compounds were reported as mTOR kinase and human lipid kinases inhibitors, it is important to measure our compounds’ activity against human lipid kinases so that we can develop a strategy to keep the malaria parasites killing activity and remove/reduce the human lipid kinase inhibitory activities.

Project Initiation Date: receipt of purchase order and the compounds Project Completion Date: 3 weeks after receipt of the compounds

SCOPE OF WORK

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 determine the kinases inhibited by malaria compounds as described herein.

Specifically, the contractor shall achieve the scope of the work to obtain kinases’ percent inhibition for 4500 data points at one concentration and 300 IC50 curves of malaria compounds. The data point is the

Title of Project:

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Version 11-30-2016-1 FAR Part 11—Describing Agency Needs kinase’s percent inhibition. It is generated through the biochemical assay for human kinase inhibition which is usually carried out at 1 uM or 500 nM concentration with n=2 (duplicate). The IC50 curve contains 10 data points with dose response (range from 2.28 nM to 46 uM) which is more labor intense.

NCATS has been regularly using both services to measure malaria compounds’ activity against human lipid kinases in previous years.

GOVERNMENT RESPONSIBILITIES

NCATS will provide the compounds to the vendor. Compounds include a series of (quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-ones with gametocytes killing activity.

DELIVERY OR DELIVERABLES

Vendor will provide the reports in 3 weeks. The reports shall be provided in Microsoft Excel table format which contains kinases’ percent inhibition for each single data point at one concentration, and 10 data points and its IC50 value for each IC50 curve.

REPORTING REQUIREMENTS

The final report of the project includes kinases’ percent inhibition at one concentration and IC50 values.

OTHER CONSIDERATIONS

No travel cost is necessary to complete this Statement of Work nor will be reimbursed by the Government.

NCATS shall have unlimited rights to and ownership of all deliverables provided under this contract, including reports, recommendations, briefings, work plans and all other deliverables. This includes the deliverables provided under the basic contract and any optional task deliverables exercised by the contracting officer. In addition, it includes any additional deliverables required by contract change. The definition of “unlimited rights” is contained in Federal Acquisition Regulation (FAR) 27.401, “Definitions.”

FAR clause 52.227-14, “Rights in Data-General”, is hereby incorporated by reference and made a part of this contract/order.

Vendor will not publish any results of the work performed from this contract.

Travel:

Data Rights:

Publications and Publicity: