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b-TrCP E3 Ligase in CLL

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
79745
Program Year/Program:
2006 / SBIR
Agency Tracking Number:
CA119605
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
PROGENRA, INC.
271A GREAT VALLEY PKWY 271A GREAT VALLEY PKWY MALVERN, PA 19355-
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2006
Title: b-TrCP E3 Ligase in CLL
Agency: HHS
Contract: 1R43CA119605-01
Award Amount: $149,800.00
 

Abstract:

DESCRIPTION (provided by applicant): a-TrCP is a recently identified component of the SCF ubiquitin E3 ligase that purportedly targets multiple proteins for ubiquitination and degradation. Some of the demonstrated targets, such as I-?B and a-catenin, are members of signal transduction pathways that have been demonstrated to be relevant to the oncogenic process. In parallel, (a-TrCP has also been identified as playing an integral role in cancer as it is induced in human breast cancer cell lines and primary tumor samples. Further evidence suggests a role for (a-TrCP in tumor progression, as a-TrCP knockout mice are hypoplastic. Ablation of a-TrCP via siRNA or expression of a dominant negative mutant reverses the oncogenic potential as it effectively suppresses growth and survival of human breast cancer cell lines. The role that a-TrCP plays in NF-?B activation and tumor progression is direct. Upon specific activation signals, I-?B becomes phosphorylated and is then ubiquitinated by SCFa-TrCP and targeted for proteasomal degradation. Augmented NF-?B activity is detected in a host of tumor cell lines and primary tumors, including prostate, colon, lung, myelomas, leukemias, carcinomas, and neuroblastoma. With this constitutive NF-?B activity, many pro-survival factors, such as anti-apoptotic bcl-2 family members, and cell cycle regulators are expressed. An increase in SCFa-TrCP is hypothesized to contribute to the elevated levels of NF-?B activity and to tumor progression. In this proposed one year Phase I, a novel E3 ligase assay for a-TrCP will be configured for high throughput screening, with the aim of using this assay to discover novel antitumor drugs that act by inhibiting the cellular activity that would normally be facilitated by wild type a-TrCP. The ultimate commercial goal of the development of an assay for a-TrCP is to discover a drug with efficacy as a single agent or a component of conjoint therapy against a host of tumors in which there is constitutive NF-?B activity.

Principal Investigator:

Benjamin Nicholson
6106446974
nicholson@progenra.com

Business Contact:

Michael Mattern
6106446974
MATTERN@PROGENRA.COM
Small Business Information at Submission:

PROGENRA, INC.
271A Great Valley Parkway MALVERN, PA 19355

EIN/Tax ID: 061660578
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No