A New High Throughput Assay for Human MDR1 Substrates

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$99,653.00
Award Year:
2001
Program:
SBIR
Phase:
Phase I
Contract:
n/a
Award Id:
53770
Agency Tracking Number:
1R43CA083551-01A2
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
1791 KAISER AVE, IRVINE, CA, 92714
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
EUGENE MECHETNER
() -
Business Contact:
(949) 474-9262
Research Institution:
n/a
Abstract
DESCRIPTION (PROVIDED BY APPLICANT): We propose to develop and validate a high throughput assay for cost/time-efficient screening and characterizing of compounds transported by human MDR1 P-glycoprotein (Pgp). The test (referred to as "the UIC2 Shift Assay") is based on a new principle: increased immunoreactivity of an anti-Pgp monoclonal antibody, UIC2, in the presence of MDR1 substrates. Our preliminary data shows the potential of the test: several new Pgp substrates have been identified using the flow cytometry version of the assay. The UIC2 Shift Assay is strictly MDR1-specific and allows for the dissection of multifactorial drug response in human malignancies. In order to develop a commercially viable, high throughput test, we designed and tested in preliminary experiments a 96-well version of the UIC2 Shift Assay. In Phase I, the design of the 96-well platform for the UIC2 Shift Assay will be optimized and validated using existing technologies (flow cytometry-based inhibition of the DiOC2 efflux test). A pilot screening will be performed on 250 well-characterized compounds (generic drugs and biochemical standards) from a commercial library. Screening results will be statistically evaluated, and the performance characteristics of the test will be determined. In Phase II, the optimized test will be validated on a large (several thousand) compound library, and a commercial kit for screening of new and characterizing of existing Pgp substrates will be developed and validated in collaboration with Beckman-Coulter, Inc. (BCI), and its subsidiary Immunotech. The technology will be compatible with BCI automated instrumentation. The project will provide a more accurate, specific and cost/time efficient assay for Pgp substrate specificity than currently available technologies. It will be used by pharmaceutical companies and academic institutions to identify new MDR1 modulators and eliminate undesired drugs - Pgp substrates from drug development programs. The potential economic effects can reach an estimated $2-3 billion annually. PROPOSED COMMERCIAL APPLICATION: We propose to develop a high throughput assay for cost/time-efficient screening and characterizing of compounds transported by human MDR1 P-glycoprotein. The automated version of this assay will be used by pharmaceutical companies and academic institutions to identify new MDR1 modulators and eliminate undesired drugs - Pgp substrates from drug development programs. The potential economic effects can reach an estimated $ 2-3 billion annually.

* information listed above is at the time of submission.

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