| Target
Information |
| Name | Fatty acid synthase |
| Type of target | Successful target |
| Synonyms | FAS |
| Fatty acyl-CoA synthetase enzyme |
| Fatty-acyl-CoA synthase |
| Yeast fatty acid synthase |
| Disease | Endometrial carcinoma
[ICD9: 182.0 ICD10: C54.1] | [1] |
Leukemia, unspecified
[ICD9: 208.9 ICD10: C91-C95] | [2] |
Malaria
[ICD9: 084 ICD10: B50-B54] | [3] |
Mesothelioma
[ICD9: 163 ICD10: C45] | [4] |
Metastatic osteosarcoma in the lung
[ICD9: 170 ICD10: C40-C41] | [5] |
Obesity
[ICD9: 278 ICD10: E66] | [6][7][8] |
Prostate cancer
[ICD9: 185 ICD10: C61] | [9][10][11] |
Tumors
[ICD9: 140-199, 210-229 ICD10: C00-C75, C7A, C7B, D10-D36, D3A] | [12][8] |
| Drug(s) | Cerulenin |  | Approved | Dramatic weight loss | [13][2][14] |
| FAS1 | | Preclinical | Fungal diseases | [15] |
| FSA2 | | Preclinical | Fungal diseases | [15] |
| BioChemical Class | Acyltransferases |
| EC Number | EC 2.3.1.85 |
| EC 2.3.1.86 |
| Pathway | Fatty acid biosynthesis |
| Insulin signaling pathway |
| Metabolic pathways |
| UniProt ID | P49327 |
| PDB Structure | 1XKT; 2CG5; 2JFD; 2JFK; 2PX6; 3HHD; 3TJM. |
| Function | Fatty acid synthetase catalyzes the formation of long- chain fatty acids from acetyl-coa, malonyl-coa and nadph. This multifunctional protein has 7 catalytic activities and an acyl carrier protein. |
| Sequence | MEEVVIAGMSGKLPESENLQEFWDNLIGGVDMVTDDDRRWKAGLYGLPRRSGKLKDLSRF
DASFFGVHPKQAHTMDPQLRLLLEVTYEAIVDGGINPDSLRGTHTGVWVGVSGSETSEAL
SRDPETLVGYSMVGCQRAMMANRLSFFFDFRGPSIALDTACSSSLMALQNAYQAIHSGQC
PAAIVGGINVLLKPNTSVQFLRLGMLSPEGTCKAFDTAGNGYCRSEGVVAVLLTKKSLAR
RVYATILNAGTNTDGFKEQGVTFPSGDIQEQLIRSLYQSAGVAPESFEYIEAHGTGTKVG
DPQELNGITRALCATRQEPLLIGSTKSNMGHPEPASGLAALAKVLLSLEHGLWAPNLHFH
SPNPEIPALLDGRLQVVDQPLPVRGGNVGINSFGFGGSNVHIILRPNTQPPPAPAPHATL
PRLLRASGRTPEAVQKLLEQGLRHSQDLAFLSMLNDIAAVPATAMPFRGYAVLGGERGGP
EVQQVPAGERPLWFICSGMGTQWRGMGLSLMRLDRFRDSILRSDEAVKPFGLKVSQLLLS
TDESTFDDIVHSFVSLTAIQIGLIDLLSCMGLRPDGIVGHSLGEVACGYADGCLSQEEAV
LAAYWRGQCIKEAHLPPGAMAAVGLSWEECKQRCPPGVVPACHNSKDTVTISGPQAPVFE
FVEQLRKEGVFAKEVRTGGMAFHSYFMEAIAPPLLQELKKVIREPKPRSARWLSTSIPEA
QWHSSLARTSSAEYNVNNLVSPVLFQEALWHVPEHAVVLEIAPHALLQAVLKRGLKPSCT
IIPLMKKDHRDNLEFFLAGIGRLHLSGIDANPNALFPPVEFPAPRGTPLISPLIKWDHSL
AWDVPAAEDFPNGSGSPSAAIYNIDTSSESPDHYLVDHTLDGRVLFPATGYLSIVWKTLA
RALGLGVEQLPVVFEDVVLHQATILPKTGTVSLEVRLLEASRAFEVSENGNLVVSGKVYQ
WDDPDPRLFDHPESPTPNPTEPLFLAQAEVYKELRLRGYDYGPHFQGILEASLEGDSGRL
LWKDNWVSFMDTMLQMSILGSAKHGLYLPTRVTAIHIDPATHRQKLYTLQDKAQVADVVV
SRWLRVTVAGGVHISGLHTESAPRRQQEQQVPILEKFCFTPHTEEGCLSERAALQEELQL
CKGLVQALQTTVTQQGLKMVVPGLDGAQIPRDPSQQELPRLLSAACRLQLNGNLQLELAQ
VLAQERPKLPEDPLLSGLLDSPALKACLDTAVENMPSLKMKVVEVLAGHGHLYSRIPGLL
SPHPLLQLSYTATDRHPQALEAAQAELQQHDVAQGQWDPADPAPSALGSADLLVCNCAVA
ALGDPASALSNMVAALREGGFLLLHTLLRGHPLGDIVAFLTSTEPQYGQGILSQDAWESL
FSRVSLRLVGLKKSFYGSTLFLCRRPTPQDSPIFLPVDDTSFRWVESLKGILADEDSSRP
VWLKAINCATSGVVGLVNCLRREPGGNRLRCVLLSNLSSTSHVPEVDPGSAELQKVLQGD
LVMNVYRDGAWGAFRHFLLEEDKPEEPTAHAFVSTLTRGDLSSIRWVCSSLRHAQPTCPG
AQLCTVYYASLNFRDIMLATGKLSPDAIPGKWTSQDSLLGMEFSGRDASGKRVMGLVPAK
GLATSVLLSPDFLWDVPSNWTLEEAASVPVVYSTAYYALVVRGRVRPGETLLIHSGSGGV
GQAAIAIALSLGCRVFTTVGSAEKRAYLQARFPQLDSTSFANSRDTSFEQHVLWHTGGKG
VDLVLNSLAEEKLQASVRCLATHGRFLEIGKFDLSQNHPLGMAIFLKNVTFHGVLLDAFF
NESSADWREVWALVQAGIRDGVVRPLKCTVFHGAQVEDAFRYMAQGKHIGKVVVQVLAEE
PEAVLKGAKPKLMSAISKTFCPAHKSYIIAGGLGGFGLELAQWLIQRGVQKLVLTSRSGI
RTGYQAKQVRRWRRQGVQVQVSTSNISSLEGARGLIAEAAQLGPVGGVFNLAVVLRDGLL
ENQTPEFFQDVCKPKYSGTLNLDRVTREACPELDYFVVFSSVSCGRGNAGQSNYGFANSA
MERICEKRRHEGLPGLAVQWGAIGDVGILVETMSTNDTIVSGTLPQRMASCLEVLDLFLN
QPHMVLSSFVLAEKAAAYRDRDSQRDLVEAVAHILGIRDLAAVNLDSSLADLGLDSLMSV
EVRQTLERELNLVLSVREVRQLTLRKLQELSSKADEASELACPTPKEDGLAQQQTQLNLR
SLLVNPEGPTLMRLNSVQSSERPLFLVHPIEGSTTVFHSLASRLSIPTYGLQCTRAAPLD
SIHSLAAYYIDCIRQVQPEGPYRVAGYSYGACVAFEMCSQLQAQQSPAPTHNSLFLFDGS
PTYVLAYTQSYRAKLTPGCEAEAETEAICFFVQQFTDMEHNRVLEALLPLKGLEERVAAA
VDLIIKSHQGLDRQELSFAARSFYYKLRAAEQYTPKAKYHGNVMLLRAKTGGAYGEDLGA
DYNLSQVCDGKVSVHVIEGDHRTLLEGSGLESIISIIHSSLAEPRVSVREG
|
| Target Validation | Click to Find Target Validation Information. |
| Inhibitor | (-)-CATECHINGALLATE | | [16] |
| 2-Hexadecynoic acid | | [17] |
| 4-hydroxy-6-nitro-3-phenylquinolin-2 (1H)-one | | [18] |
| 4-hydroxy-8-nitro-3-phenylquinolin-2 (1H)-one | | [18] |
| BIOCHANIN | | [16] |
| C75 | | [19] |
| C75 | | [20] |
| Cerulenin | | [13][2][14] |
| Cerulenin | | [21] |
| EPICATECHIN GALLATE | | [16] |
| EPIGALOCATECHIN GALLATE | | [16] |
| FAS1 | | [15] |
| FISETIN | | [16] |
| FSA2 | | [15] |
| GALLOCATECHIN GALLATE | | [16] |
| MORIN | | [16] |
| PA-824 | | [22] |
| Cross References |
3D Structure
Related Literature
On-Line
Medical Dictionary |
| Ref 1 | Inhibition of tumor-associated fatty acid synthase activity antagonizes estradiol- and tamoxifen-induced agonist transactivation of estrogen receptor (ER) in human endometrial adenocarcinoma cells. Oncogene. 2004 Jun 17;23(28):4945-58. To Reference |
| Ref 2 | Proliferation inhibition and apoptosis induction of K562 cells by fatty acid synthase inhibitor--cerulenin. Zhonghua Xue Ye Xue Za Zhi. 2000 May;21(5):244-6. To Reference |
| Ref 3 | The cloning and expression of Pfacs1, a Plasmodium falciparum fatty acyl coenzyme A synthetase-1 targeted to the host erythrocyte cytoplasm. J Mol Biol. 1999 Aug 6;291(1):59-70. To Reference |
| Ref 4 | Increased fatty acid synthase is a therapeutic target in mesothelioma. Clin Cancer Res. 2001 Jan;7(1):153-7. To Reference |
| Ref 5 | Fas expression inversely correlates with metastatic potential in osteosarcoma cells. Oncol Rep. 2002 Jul-Aug;9(4):823-7. To Reference |
| Ref 6 | Regulation of fatty acid synthase (FAS). Prog Lipid Res. 1997 Mar;36(1):43-53. To Reference |
| Ref 7 | Weight reduction by Chinese medicinal herbs may be related to inhibition of fatty acid synthase. Life Sci. 2004 Mar 26;74(19):2389-99. To Reference |
| Ref 8 | A fatty acid synthase blockade induces tumor cell-cycle arrest by down-regulating Skp2. J Biol Chem. 2004 Jul 16;279(29):30540-5. Epub 2004 May 11. To Reference |
| Ref 9 | Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer. Int J Cancer. 2002 Mar 1;98(1):19-22. To Reference |
| Ref 10 | Increased fatty acid synthase expression and activity during progression of prostate cancer in the TRAMP model. Prostate. 2003 Nov 1;57(3):245-54. To Reference |
| Ref 11 | Fatty acid synthase: a metabolic oncogene in prostate cancer? J Cell Biochem. 2004 Jan 1;91(1):47-53. To Reference |
| Ref 12 | Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology. Nutrition. 2000 Mar;16(3):202-8. To Reference |
| Ref 13 | Inhibition of Fatty Acid Biosynthesis Prevents Adipocyte Lipotoxicity on Human Osteoblasts In Vitro. J Cell Mol Med. 2009 Mar 27. [Epub ahead of print] To Reference |
| Ref 14 | The antibiotic cerulenin, a novel tool for biochemistry as an inhibitor of fatty acid synthesis. Bacteriol Rev. 1976 Sep;40(3):681-97. To Reference |
| Ref 15 | Novel antifungal agents, targets or therapeutic strategies for the treatment of invasive fungal diseases: a review of the literature (2005-2009). Rev Iberoam Micol. 2009 Mar 31;26(1):15-22. Epub 2009 May 7. To Reference |
| Ref 16 | J Med Chem. 2006 Jun 1;49(11):3345-53.Inhibition of Plasmodium falciparum fatty acid biosynthesis: evaluation of FabG, FabZ, and FabI as drug targets for flavonoids. To Reference |
| Ref 17 | Bioorg Med Chem. 2010 Nov 1;18(21):7475-85. Epub 2010 Sep 18.2-Hexadecynoic acid inhibits plasmodial FAS-II enzymes and arrests erythrocytic and liver stage Plasmodium infections. To Reference |
| Ref 18 | Bioorg Med Chem Lett. 2006 Sep 1;16(17):4620-3. Epub 2006 Jun 19.3-Aryl-4-hydroxyquinolin-2(1H)-one derivatives as type I fatty acid synthase inhibitors. To Reference |
| Ref 19 | C75 increases peripheral energy utilization and fatty acid oxidation in diet-induced obesity. Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9498-502. Epub 2002 Jun 11. To Reference |
| Ref 20 | Obesity: pathophysiology and clinical management. Curr Med Chem. 2009;16(4):506-21. To Reference |
| Ref 21 | 20511185 To Reference |
| Ref 22 | Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8. To Reference |
