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BioAssay: AID 602265

Summary assay for small molecule inhibitors of the thioesterase domain of fatty acid synthase

This study will focus on developing drug-like inhibitors/probes against fatty acid synthase, an enzyme that is essential for growth of solid tumors. Notably, FAS has only marginal importance in adults because dietary fat provides for normal physiology. The link between FAS and cancer was uncovered in 1994 when Frank Kuhajda found that the OA-519 antigen, a marker for poor prognosis in breast more ..
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AID: 602265
Data Source: Burnham Center for Chemical Genomics (SBCCG-A783-FAS-TE-Summary-Assay)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2012-02-17
Target
Depositor Specified Assays
Show more
AIDNameTypeComment
602261uHTS identification of small molecule inhibitors of the thioesterase domain of fatty acid synthase via a fluorescence intensity assayscreeningPrimary Screen
624325Single concentration confirmation of uHTS inhibitor hits of the thioesterase domain of fatty acid synthase via a fluorescence intensity assayscreening
624326Dose response confirmation of small molecule inhibitors of the thioesterase domain of fatty acid synthase via a kinetic, fluorescence intensity assayconfirmatory
624327Dose response confirmation of uHTS inhibitor hits of the thioesterase domain of fatty acid synthase via a fluorescence intensity assayconfirmatory
651670SAR analysis of small molecule inhibitors of the thioesterase domain of fatty acid synthase via a fluorescence intensity assayconfirmatory
652164SAR confirmation of small molecule inhibitors of the thioesterase domain of fatty acid synthase via a fluorescence intensity assayconfirmatory
652165SAR confirmation of small molecule inhibitors of the thioesterase domain of fatty acid synthase via a kinetic, fluorescence intensity assayconfirmatory
652286SAR confirmation of small molecule inhibitors of the thioesterase domain of fatty acid synthase via a kinetic, fluorescence intensity assay, round 2confirmatory
652287SAR confirmation of small molecule inhibitors of the thioesterase domain of fatty acid synthase via a fluorescence intensity assay, round 2confirmatory
Description:
Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG)
Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego, CA)
Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Number: 1R03MH095532-01
Assay Provider: Dr. Jeffrey Smith, Sanford-Burnham Medical Research Institute, San Diego CA

This study will focus on developing drug-like inhibitors/probes against fatty acid synthase, an enzyme that is essential for growth of solid tumors. Notably, FAS has only marginal importance in adults because dietary fat provides for normal physiology. The link between FAS and cancer was uncovered in 1994 when Frank Kuhajda found that the OA-519 antigen, a marker for poor prognosis in breast and prostate cancer, is actually fatty acid synthase. A number of subsequent immunohistochemical analyses showed that increased expression of FAS is a hallmark of all major cancers. The correlation between expression of FAS and poor prognosis strongly suggests that this enzyme is mechanistically linked to disease progression, providing a strong rationale for pursuing the development of FAS inhibitors.

The FAS protein contains six enzymatic domains and an acyl-carrier protein (ACP). The final enzymatic pocket is a thioesterase, which liberates the final product (palmitate) from its link to the ACP. It is the thioesterase domain of FAS which we plan to target here. To our knowledge, no thioesterase (TE) has ever been targeted for drug development. The goal of this high-throughput assay is to identify hit compounds for the FAS-TE domain.
Protocol
Please see pertinent AIDs: 602261
Comment
Probe molecules are defined as the positives of this assay and assigned a score of 100. Testing has not progressed to the point where a probe molecule has been identified.
Additional Information
Grant Number: 1R03MH095532-01

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