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DEVELOPING SMALL MOLECULE BIFUNCTIONAL RAS INHIBITORS

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: CA74702-01A1
Agency Tracking Number: 39361
Amount: $100,000.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: N/A
Solicitation Number: N/A
Timeline
Solicitation Year: N/A
Award Year: 1997
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
200 BOSTON AVE, STE 3000
Medford, MA 02155
United States
DUNS: N/A
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 PAKULA, ANDREW A
 () -
Business Contact
Phone: (617) 393-8030
Research Institution
N/A
Abstract

This proposal focuses on the development of a novel bifunctional drug screening assay for the discovery of specific inhibitors of human h-Ras protein utilizing the proprietary ATLAS (any target ligand affinity screen) approach, which was originally developed by th P.I., Dr. Pakula Ras is a member of a large family of related intracellular proteins, and is potentially an important therapeutic target for diseases associated with cellular proliferation. The approach depends initially on identifying auxiliary and inhibitory ligands for adjustment binding sites on Ras protein. The preparation of a bifunctional molecular comprised of the two small molecular ligands attached through a linker group will then be carried out. It is anticipated that the bifunctional molecule, obtained by tethering the two small ligands, will have a much higher affinity for the Ras protein. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 179 --PROJECT NUMBER......1 R43 CA74713-01A1 INVESTIGATOR NAME/ADDRESS FY 97 TSAI, DAVID M IRG/INTRAMURAL UNIT..ZRG2 AMBRYX BIOTECHNOLOGY, INC AWARD AMOUNT......... $100,000 2500 TOWNSGATE ROAD, UNIT C WESTLAKE VILLAGE, CA 91361 PERFORMING ORGANIZATION: AMBRYX BIOTECHNOLOGY, INC. TITLE APOPTOSIS INDUCING PROTEINS AS ANTICANCER AGENT NO ABSTRACT ON FILE $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 180 --PROJECT NUMBER......1 R43 CA74717-01 INVESTIGATOR NAME/ADDRESS FY 97 RISDON, GRANT H IRG/INTRAMURAL UNIT..ZRG2 CELLPRO, INCORPORATED AWARD AMOUNT......... $75,543 22215 26TH AVE SE BOTHELL, WA 98021 PERFORMING ORGANIZATION: CELLPRO, INC. TITLE EX-VIVO GROWTH AND PRIMING OF HUMAN DENDRITIC CELLS NO ABSTRACT ON FILE $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 181 --PROJECT NUMBER......1 R43 CA74725-01 INVESTIGATOR NAME/ADDRESS FY 97 HEVEZI, PETER A IRG/INTRAMURAL UNIT..ZRG3 KOSAN BIOSCIENCES INC AWARD AMOUNT......... $100,000 1450 ROLLINS RD BURLINGAME, CA 94010 PERFORMING ORGANIZATION: KOSAN BIOSCIENCES TITLE LIBRARIES FROM THE RAPAMYCIN POLYKETIDE SYNTHASE ABSTRACT: The long term goal of this project is to generate libraries of novel polyketides for anticancer drug screening. Libraries will be constructed by manipulation of the gene cluster encoding the biosynthetic enzymes for the polyketide immunosuppressant, rapamycin. The rapamycin ployketide synthase (PKS) is an ideal candidate for such library development due to its large size (14 modules), modular layout, unusual starter unit and novel synthetic final step. A collection of mutant gene clusters will be made by varying the size and or the activities within each gene cluster ultimately using a combinatorial approach. The resulting engineered PKS gene clusters will be expressed in a specially constructed Streptomyces host/vector system. Polyketides are potent pharmacophores and it is anticipated that these libraries will prove extremely valuable as a source of lead compounds. Phase I of this project involves cloning the rapamycin PKS gene cluster from Streptomyces hygroscopicus and functional expression of a truncated gene cluster containing the first three modules in the heterologous Streptomyces host. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 182 --PROJECT NUMBER......1 R43 CA74746-01A1 INVESTIGATOR NAME/ADDRESS FY 97 SOLBERG, KEITH A IRG/INTRAMURAL UNIT..ZRG7 INDIANA UNIV CYCLOTRON FACILIT AWARD AMOUNT......... $99,879 2401 MILO B SAMPSON LANE BLOOMINGTON, IN 47408 PERFORMING ORGANIZATION: REAL TIME IMAGING, INC. TITLE REAL TIME X RAY IMAGING ABSTRACT: "We propose the development of an X-ray imaging system based on a xenon- filled gas ionization counter as an image intensifier with high photon output.Modern microfabrication techniques will be used to construct gas ionization counters with an active element pitch of 100 microns, which would be imaged in prototype form by a CCD camera. This system will be real-time, digital, inexpensive, and will achieve a position resolution significantly less than 100 microns. imaging the light, and not the charge, will allow the readout technology to be imported as turnkey system with no development costs. Compared to conventional scintillator screens, this device will have a much higher photon output due to the charge multiplication process inherent to a gas ionization counter. In addition, the atomic spectrum of excited xenon has strong transitions in the near infrared (IR) region, where CCD devices have large quantum efficiency. A clinical device would ultimately be built around the use of inexpensive CCDs, now being developed for application to filmless cameras." $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 183 --PROJECT NUMBER......1 R43 CA74754-01 INVESTIGATOR NAME/ADDRESS FY 97 ROY, RITA T IRG/INTRAMURAL UNIT..ZRG4 MEDICAL CONSUMER MEDIA AWARD AMOUNT......... $100,000 6707 DEMOCRACY BLVD BETHESDA, MD 20817 PERFORMING ORGANIZATION: MEDICAL CONSUMER MEDIA TITLE WWW DISTANCE LEARNING FOR ONCOLOGY NURSING EDUCATION NO ABSTRACT ON FILE $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 184 --PROJECT NUMBER......1 R43 CA74762-01 INVESTIGATOR NAME/ADDRESS FY 97 BOERRIGTER, MICHAEL E IRG/INTRAMURAL UNIT..ZRG2 LEVEN, INC AWARD AMOUNT......... $79,350 421 CHESTERFIELD ROAD BOGART, GA 30622 PERFORMING ORGANIZATION: LEVEN, INC. TITLE VALIDATION OF A TRANSGENIC MOUSE MUTATION MODEL ABSTRACT: The purpose of this project is to demonstrate the feasibility to detect organ-specific mutagenic responses to a variety of chemical compounds in relation to organ-specific carcinogenic action. A transgenic mouse model was constructed carrying multiple copies of a plasmid, containing the bacterial lacZ marker gene, integrated head-to-tail in the genome of all organs and tissues. Highly efficient protocols for the rescue of these vectors from their integrated state have been developed. The detection of mutations in the lacZ reporter gene is facilitated by a positive selection system. The use of this novel lacZ plasmid--based transgenic mouse model makes it now possible to study DNA damage and mutant induction in the same animal and in the same organ after treatment with low doses of a particular carcinogenic agent. This new in vivo transgenic mouse mutagenicity assay provides an unique opportunity to study the induction of tissue-specific mutations that reflect the integration of pharmacokinetics, biotransformation, DNA repair responses, and tissue susceptibility.

* Information listed above is at the time of submission. *

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