SOLICITATION NOTICE
68 -- Chemical Compounds
- Notice Date
- 10/10/2002
- Notice Type
- Solicitation Notice
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Research Contracts Br., 6120 Executive Blvd. EPS Suite 600, Rockville, MD, 20852
- ZIP Code
- 20852
- Solicitation Number
- NCI-30002-NG
- Archive Date
- 11/8/2002
- Point of Contact
- Malinda Holdcraft, Purchasing Agent, Phone (301) 402-4509, Fax (301) 402-4513, - Caren Rasmussen, Lead Contract Specialist, Phone (301) 402-4509, Fax (301) 402-4513,
- E-Mail Address
-
holdcram@exchange.nih.gov, cr214i@nih.gov
- Description
- The National Cancer Institute (NCI), Center for Cancer Research (CCR), Cancer Therapeutics Branch (CTB) plans to procure supplies and services for Synthesis of 2'-Alkoxy, 3'- deoxyphosphatidylinsolitol ether lipid analogues, from Axxora Laboratories, LLC, 6181 Cornerstone Court East, Suite 103, San Diego, California 92121-4727. The supplies and services herein are being procured in accordance with the simplified acquisition procedures authorized in FAR Part 13. The North American Industry Classification System Code is 325411 and the business size standard is 750 employees. The Signal Transduction Section of the CTB, CCR, NCI studies signaling pathways involved in tumorigenesis and the therapeutic resistance of solid tumors. The goals of the section are to identify clinically relevant kinases whose modification may alter tumor formation and/or growth, and to develop approaches to inhibit these identified kinases. Akt (or protein kinase B (PKB)) is a well-characterized serine/threonine kinase that promotes cellular survival. Akt can be activated in response to growth stimuli as well as stressful stimuli. Activation requires phosphorylation of 2 amino acids, one in the activation domain and one in the C-terminal hydrophobic motif. Phosphorylation of the site in the activation domain is dependent on the products of an upstream kinase, phosphatidylinositol 3-kinase (PI3-K), phosphatidylinositol 3,4 bisphosphate (PIP2) and phosphatidylinositol 3,4,5 trisphosphate (PIP3). PIP2 and PIP3 bind to pleckstrin homology (PH) domain of Akt, which results in translocation of Akt to the plasma membrane, where the two phosphorylation events subsequently occur. Analysis of mice and human tissues show that Akt activation plays a role in tumor biology. In an effort to develop small molecules against Akt without depending on crystallographic information on the structure of Akt, NCI is collaborating with Dr. Alan Kozikowski of Georgetown University and, scientic advisor to Axxora Laboratories, LLC, who has molecularly modeled the interaction of PIP2 and PIP3 with the PH domain of Akt, and has synthesized phosphatidylinositol (PI) ether lipid analogues that were designed to inhibit the binding of PIP2 and PIP3 to the PH domain of Akt, thereby inhibiting Akt activity. NCI has screened 25 PI analogues that differed in substitutions at the inositol ring, and have identified 5 effective analogues with similar 2-alkoxy, 3'- deoxy substitutions on the inositol ring. Each of these compounds inhibits Akt phosphorylation and activity in lung cancer and breast cancer cell lines that have high levels of endogenous Akt activity. These compounds work effectively, with IC50 from 600nM-3?M. Data suggest that these compounds might have utility as future cancer therapies. The biologic studies and animal studies require synthesis of approximately 100 mg of each effective compound (SH5, 6, 23, 24, and 25) as well as 100 mg of an ether lipid analogue that lacks an inositol ring and therefore serves as a negative control. Additionally, 10 mg amounts of each of the inositol head groups are required. The NCI and Georgetown University are co-inventors of these compounds, and they can only be made efficiently by the team at Axxora Laboratories with the consultation of Dr. Kozikowski, developer of these compounds. The compounds could eventually be used to treat cancer or other diseases characterized by Akt activation. Period of Performance: Upon award of purchase order through six (6) months; FAR Clause 52.217-8 Option to Extend Services (November 1999) applies to this requirement. Axxora Laboratories, LLC., is the only source known to the NCI that can provide the expertise to synthesize the compounds needed to continue the existing experiment in progress. Dr. Kozikowski is the director of the Drug Discovery Program of Georgetown University and founder of Axxora Laboratories, LLC, and has published extensively on the synthesis of compounds designed to inhibit various molecular targets. Importantly, Dr. Kozikowski was the first to discover and synthesize 3' deoxyphosphatidylinositol ether lipid analogues that serve as precursors for the 2'-alkoxy-, 3'- deoxyphosphatidylinositol ether lipid analogues. Dr. Kozikowski's compound synthesis is innovative, elegant, consistent, and reliable. The compounds themselves are unique and have not been described in the literature. This notice of intent is not a request for competitive quotations. However, if any interested party believes it can meet the above requirements, it may submit a statement of capabilities. The capability statement and any other furnished information must be in writing and must contain material in sufficient detail to allow NCI to determine if the party can fully meet the requirements herein. Capability statements must be received in the contracting office by 1:00 PM EDT (local Washington DC time) on October 25, 2002. If you have any questions, please contact Malinda Holdcraft, Purchasing Agent via electronic mail at holdcram@exchange.nih.gov or by fax 301-402-4513. A determination by the Government not to compete this proposed requirement based on responses to this notice is solely within the discretion of the Government. Information received shall be considered solely for the purpose of determining whether to conduct a competitive requirement. No collect calls will be accepted.
- Place of Performance
- Address: NIH/NCI, 9000 Rockville Pike, Bethesda, MD
- Zip Code: 20892
- Country: USA
- Zip Code: 20892
- Record
- SN00185996-W 20021012/021010213142 (fbodaily.com)
- Source
-
FedBizOpps.gov Link to This Notice
(may not be valid after Archive Date)
| FSG Index | This Issue's Index | Today's FBO Daily Index Page |