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 ..
Target
| Sequence: fatty acid synthase [Homo sapiens] Protein Family: PKS Gene:FASN Related Protein 3D Structures |
Depositor Specified Assays
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| AID | Name | Type | Comment |
|---|---|---|---|
| 602261 | uHTS identification of small molecule inhibitors of the thioesterase domain of fatty acid synthase via a fluorescence intensity assay | screening | Primary Screen |
| 624326 | Dose response confirmation of small molecule inhibitors of the thioesterase domain of fatty acid synthase via a kinetic, fluorescence intensity assay | confirmatory | |
| 624327 | Dose response confirmation of uHTS inhibitor hits of the thioesterase domain of fatty acid synthase via a fluorescence intensity assay | confirmatory | |
| 624325 | Single concentration confirmation of uHTS inhibitor hits of the thioesterase domain of fatty acid synthase via a fluorescence intensity assay | screening | |
| 651670 | On Hold | ||
| 652164 | On Hold | ||
| 652165 | On Hold | ||
| 652286 | On Hold | ||
| 652287 | On Hold |
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.
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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