Contact Points
The National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH) seeks to transform the translational science process so that new treatments and cures for disease can be delivered to patients faster. NCATS, one of twenty-seven Institutes and Centers (ICs) at NIH, strives to develop innovations to reduce, remove or bypass costly and time-consuming bottlenecks in the translational research pipeline in an effort to speed the delivery of new drugs, diagnostics and medical devices to patients. 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.
The Division of Preclinical Innovation (DPI) group at NCATS is currently exploring studies related to the diffuse midline gliomas such as diffuse intrinsic pontine glioma (DIPG), which are incurable lethal central nervous system tumors that occur during childhood. High throughput single-agent and combination drug screenings led to the identification of promising drug combinations, therefore highlighting potential therapeutic strategies toward the treatment of DIPG. One such combination involves heat shock protein 70 (Hsp70) and dCTP pyrophosphatase 1 (DCTPP1) inhibitor Minnelide and histone deacetylase (HDAC) inhibitor Panobinostat. The acquisition of two grams of Minnelide would allow to further investigate its activity profile in combination with HDAC inhibitors in animal models.
GNE-618 is an inhibitor of nicotinamide phosphoribosyl transferase (NAMPT), the rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD+) salvage pathway, currently in preclinical development. Our team has shown that combining PARP inhibitors and NAMPT inhibitors resulted in robust synergy in in vitro models of Ewing sarcoma through decreased PAR activity, increased DNA damage and apoptosis, and that the combination retained efficacy in multiple in vivo models. These data suggest that combining PARP inhibitors with NAMPT inhibitors may be a promising strategy for Ewing sarcoma. (Clin Cancer Res. 2017 Dec 1;23(23):7301-7311). The acquisition of ten grams of GNE-618 would allow to further investigate its activity profile in combination with poly ADP ribose polymerase (PARP) inhibitors in animal models.
Purpose/Objective:
Specifically, the DPI requires contractor services to provide for:
1). Two (2) grams of Minnelide (CAS: 1254702-87-8), for the DIPG, which shall be provided with chemical purity exceeding 95% and enantiopurity exceeding 95%, and
2). Ten (10) grams of GNE-618 (CAS: 1362151-42-5), for the Re-synthesis Project with the DPI, which shall will be provided with chemical purity exceeding 95%.
Statement of Work:
The contractor will perform pharmacokinetic assessment of desired compounds within CD-1 male mice, with an emphasis being placed on the plasma exposure of the desired compounds over a given time frame. These studies will commence within 5 business days of receipt of the compounds by the contractor. These studies will be completed within 10 business days of receipt of the compounds.
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 Statement of Work described herein.
Specifically, the Contractor shall be able to provide the following services:
- Characterization and delivery of two grams of Minnelide (CAS: 1254702-87-8).
- Chemical purity to exceed 95% and enantiopurity to exceed 95%.
- The appropriate documentation (LC-MS trace, proton NMR, carbon NMR spectra, chiral LC-MS) demonstrating these purity levels will be provided.
- Characterization and delivery of ten grams of GNE-618 (CAS: 1362151-42-5).
- Chemical purity to exceed 95%.
- The appropriate documentation (LC-MS trace, proton NMR, carbon NMR spectra) demonstrating these purity levels will be provided.
LEVEL OF EFFORT: N/A
GOVERNMENT RESPONSIBILITIES: Government will not furnish property, facilities, workspace, computers, or other equipment. Contractor will not use federal facilities. Government will have the responsibility to review and approve the final report. Government will have the responsibility to provide sufficient quantities of the lead compound in order to contractor to accomplish the necessary work
DELIVERY OR DELIVERABLES
- The Contractor will deliver two grams of Minnelide (CAS: 1254702-87-8) in a clearly labeled bottle or vial. The material will be provided with chemical purity exceeding 95% and enantiopurity to exceed 95%. The Contractor will provide a copy of the certificate of analysis including the analytical data demonstrating the purity of the final product.
- The Contractor will deliver ten grams of GNE-618 (CAS: 1362151-42-5) in a clearly labeled bottle or vial. The material will be provided with chemical purity exceeding 95%. The Contractor will provide a copy of the certificate of analysis including the analytical data demonstrating the purity of the final product.
REPORTING REQUIREMENTS: Contractor will provide monthly updates on the progress of the project, or more often as appropriate
OTHER CONSIDERATIONS
Travel: N/A
Key Personnel: N/A
Information System Security Plan: N/A
Data Rights: Data is the right of NCATS.
Section 508—Electronic and Information Technology Standards: NA
Publications and Publicity: Contractor will not publish results of the work.
Confidentiality of Information: Contractor will keep the results of the acquisition confidential.
Delivery/Contract Type: The performance period and delivery shall be completed within 30 days after contractor receipt of an order and the material to be analyzed. A Fixed-Price type of Purchase Order contract award is anticipated as a result of this RFQ not to exceed the Simplified Acquisition Threshold of $250,000.
Summary Statement:
This notice is NOT a request for competitive proposals or quotations.
It is anticipated that a solicitation will be issued on or about March 27, 2020. Interested parties may request a copy of the solicitation or identify their interest and capability by contacting the contract specialist specified in this announcement.
Interested parties may identify in writing their interest and capability in response to this requirement. Responses to this notice shall contain sufficient information to establish the interested parties’ bona-fide capabilities for fulfilling the requirement and include: unit price, list price, shipping and handling costs, the delivery period after contract award, the prompt payment discount terms, the F.O.B. Point (Destination or Origin), the Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size. All offerors must have an active registration in the System for Award Management (SAM) www.sam.gov.
All responses must be received by closing date and must reference the announcement. Responses may be submitted electronically to the attention of the contract specialist. Fax responses will not be accepted.
All responsible sources may submit a bid, proposal, or quotation which shall be considered by the agency.