D Attachment 1 SOW_GSK kinase.pdf

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

STATEMENT OF WORK (SERVICES)

(SOW)

GENERAL INFORMATION

Title of Project:

Determining Kinases Inhibition by GSK3 inhibitors

Statement of Need and Purpose:

NCATS requires contractor results of profiling GSK3 inhibitors against a panel of human kinases for 5000 data points at one concentration and 400 IC50 curves.

Background Information and Objective:

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.

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 chemical material as a probe to investigate the mechanisms of diseases and to potentially assist in the development of new methods of treating such diseases.

CTNNB1 syndrome is a severe rare monogenetic neurodevelopmental disorder with no current treatment.

It is characterized by cognitive and motor disabilities that severely impact the quality of life for these patients. Studies from Tufts University showed that GSK3 inhibifors correct core molecular and behavioral phenotypes in the CTNNB1 preclinical models. Recently, NCATS has accepted a proposal from Michele Jacob from Tufts University and Michel Weiwer from Broad Institute of MIT and Harvard University to develop a novel series of GSK3 inhitors for treating CTNNB1 syndrome. It is important to measure newly developed compounds’ activity against human lipid kinases so that we can develop a strategy to keep the GSK3 activity and remove/reduce other human kinase inhibitory activities.

Period of Performance:

09/23/2024 – 10/22/2024

SCOPE OF WORK

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 determine the kinases inhibited by malaria compounds as described herein.

Specific Requirements:

Specifically, the contractor shall achieve the scope of the work to obtain kinases’ percent inhibition for 5000 data points at one concentration and 400 IC50 curves of malaria compounds. The data point is the 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.

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

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

LEVEL OF EFFORT:

N/A

GOVERNMENT RESPONSIBILITIES

NCATS will provide the compounds to the vendor.

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

Travel:

N/A

Key Personnel:

N/A

Information System Security Plan:

Data Rights:

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.

Section 508—Electronic and Information Technology Standards:

N/A

Publications and Publicity:

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

Confidentiality of Information: