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DRUG:

cerulenin

Associations
Trials
Company:
Fermentek
Drug class:
Fatty acid inhibitor
Associations
Trials
1m
Self-Resistance Gene-Guided Discovery of the Molecular Basis for Biosynthesis of the Fatty Acid Synthase Inhibitor Cerulenin. (PubMed, Angew Chem Int Ed Engl)
Using in vitro assays, we further validated the roles of amidotransferase CerD in amidation, and oxidase CerF and reductase CerE in the final two-electron oxidation and enone reduction steps towards 1. These findings expand our understanding of complex tailoring modifications in highly reducing PKS pathways and pave the way for the engineered biosynthesis of cerulenin analogues.
Journal
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FASN (Fatty acid synthase)
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cerulenin
2ms
Fatty Acid Synthase Inhibitor Cerulenin Hinders Liver Cancer Stem Cell Properties through FASN/APP Axis as Novel Therapeutic Strategies. (PubMed, J Lipid Res)
In addition, sorafenib, a multikinase inhibitor used as targeted therapy for advanced HCC, was employed in combination with cerulenin, demonstrating a great synergistic effect, particularly in CSCs. We found that APP plays a crucial role in CSCs' characteristics that can be inhibited by cerulenin. By focusing on FA metabolism, this study identified the FASN/APP axis as a viable target to develop a more potent therapy strategy for advanced HCC.
Journal • Cancer stem
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FASN (Fatty acid synthase)
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sorafenib • cerulenin
4ms
FAS Inhibited Proteomics and Phosphoproteomics Profiling of Colorectal Cancer Spheroids Shows Activation of Ferroptotic Death Mechanism. (PubMed, J Proteome Res)
These results show that HT-29 spheroids exposed to cerulenin or TVB-2640 are undergoing a ferroptotic death mechanism. The data were deposited to the ProteomeXchange Consortium via the PRIDE repository with the identifier PXD050987.
Journal
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FASN (Fatty acid synthase)
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denifanstat (TVB-2640) • cerulenin
11ms
Fatty Acid Synthase Inhibitors Enhance Microtubule-Stabilizing and Microtubule-Destabilizing Drugs in Taxane-Resistant Prostate Cancer Cells. (PubMed, ACS Pharmacol Transl Sci)
In the current study, we investigated five FASN inhibitors-cerulenin, orlistat, triclosan, thiophenopyrimidine fasnall, and pyrazole derivative TVB-3166 for their potential to synergize with docetaxel (a microtubule stabilizer) and vinblastine (a microtubule destabilizer) in TxR cell lines. Orlistat, TVB-3166, and fasnall synergistically inhibited cell viability when combined with docetaxel and vinblastine in PC3-TxR and DU145-TxR cells. Confocal microscopy and immunoblot with an antidetyrosinated tubulin antibody demonstrated that enhanced microtubule stability was induced by the combined treatment of FASN inhibitors and docetaxel compared with docetaxel alone, while combinations of FASN inhibitors with vinblastine diminished microtubule stability compared to vinblastine alone.
Journal
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FASN (Fatty acid synthase)
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FASN overexpression
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docetaxel • vinblastine • cerulenin
11ms
Lipidomics Profiling Reveals Differential Alterations after FAS Inhibition in 3D Colon Cancer Cell Culture Models. (PubMed, J Proteome Res)
TVB-2640 causes higher abundances of polyunsaturated fatty acids (PUFAs) whereas cerulenin causes a decreased abundance of PUFAs. The increase in PUFAs in TVB-2640 exposed spheroids indicates it is causing cells to die via a ferroptotic mechanism rather than a conventional apoptotic or necrotic mechanism.
Preclinical • Journal
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FASN (Fatty acid synthase)
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denifanstat (TVB-2640) • cerulenin
2years
Cerulenin suppresses ErbB2-overexpressing breast cancer by targeting ErbB2/PKM2 pathway. (PubMed, Med Oncol)
Finally, the inhibitory of cerulenin on colony formation, migration, invasion and glycolysis, as well as protein levels of EMT markers were rescued by replenishing with PKM2. These findings illustrated that cerulenin inhibits proliferation, migration, invasion and glycolysis by targeting ErbB2/PKM2 pathway in ErbB2-overexpressing breast cancer cells.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • MMP2 (Matrix metallopeptidase 2) • FASN (Fatty acid synthase) • MMP9 (Matrix metallopeptidase 9) • SNAI2 (Snail Family Transcriptional Repressor 2) • PKM (Pyruvate Kinase M1/2)
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HER-2 overexpression
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cerulenin
over2years
FASN promotes lymph node metastasis in cervical cancer via cholesterol reprogramming and lymphangiogenesis. (PubMed, Cell Death Dis)
More importantly, knockdown of FASN with FASN shRNA or the inhibitors C75 and Cerulenin dramatically diminished LNM in vivo, suggesting that FASN plays an essential role in LNM of CC and the clinical application potential of FASN inhibitors. Taken together, our findings uncover a novel molecular mechanism in LNM of CC and identify FASN as a novel prognostic factor and potential therapeutic target for LNM in CC.
Journal
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FASN (Fatty acid synthase) • IGFBP3 (Insulin-like growth factor binding protein 3)
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cerulenin
4years
RNA-seq reveals novel mechanistic targets of withaferin A in prostate cancer cellss. (PubMed, Carcinogenesis)
WA was a superior inhibitor of cell proliferation and fatty acid synthesis in comparison with known modulators of fatty acid metabolism including cerulenin and etomoxir. Intraperitoneal WA administration to Hi-Myc transgenic mice (0.1 mg/mouse, three times/week for 5 weeks) also resulted in a significant decrease in circulating levels of total free fatty acids and phospholipids, and expression of ACLY, ACC1, FASN, and CPT1A proteins in the prostate in vivo.
Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • FASN (Fatty acid synthase)
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MYC expression
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cerulenin
4years
Protein Palmitoylation Regulates Cell Survival by Modulating XBP1 Activity in Glioblastoma Multiforme. (PubMed, Mol Ther Oncolytics)
Inhibition of protein palmitoylation with substrate-analog inhibitors, that is, 2-bromopalmitate, cerulenin, and tunicamycin, induced G cell cycle arrest and cell death in GBM cells through enhanced endoplasmic reticulum (ER) stress...Further analysis revealed was the accumulation of SUMOylated XBP1 (X-box binding protein 1) and its transcriptional repression, along with a reduction in XBP1 palmitoylation. Taken together, the present results indicate that protein palmitoylation plays an important role in the survival of GBM cells, further providing a potential therapeutic strategy for GBM.
Journal
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XBP1 (X-box-binding protein 1)
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cerulenin
over4years
Withania somnifera root extract inhibits fatty acid synthesis in prostate cancer cells. (PubMed, J Tradit Complement Med)
WRE exhibited greater potency for fatty acid synthesis inhibition at equimolar concentration than cerulenin and etomoxir...However, overexpression of only c-Myc conferred protection against clonogenic cell survival and lipogenesis inhibition by WRE. In conclusion, these results indicate that WRE is a novel inhibitor of fatty acid synthesis in human prostate cancer cells.
Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • FASN (Fatty acid synthase)
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MYC overexpression
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cerulenin
over4years
Leelamine is a Novel Lipogenesis Inhibitor in Prostate Cancer Cells In Vitro and In Vivo. (PubMed, Mol Cancer Ther)
LLM was superior to another fatty acid synthesis inhibitor (cerulenin) for suppression of total free fatty acid levels...LLM-mediated suppression of intracellular levels of total free fatty acids and neutral lipids was partly attenuated by overexpression of SREBP1. In conclusion, these results indicate that LLM is a novel inhibitor of SREBP1-regulated fatty acid/lipid synthesis in prostate cancer cells that is not affected by androgen receptor status.
Preclinical • Journal
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AR (Androgen receptor) • FASN (Fatty acid synthase)
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cerulenin
5years
Identification of FASN-Dependent Onco-Metabolic Regulation of the Pentose Phosphate Pathway (PPP) and Nucleotide Metabolism in Non-Hodgkin Lymphoma (NHL) (ASH 2019)
FASN small molecule inhibitors cerulenin, orlistat, TVB3657 and TVB3166 were evaluated using a diverse panel of B cell NHL lines and primary NHL cells for the impact on FASN inhibition signaling & induction of cell death (MTT, caspases & AnnexinV/PI)...All responses were sensitive to inhibition by PI3K inhibition (e.g., BKM120) with co-targeting via FASN & PI3K inhibition resulting in markedly increased oxidative stress, loss of mitochondrial membrane potential & synergistic cell death in NHL cell lines and primary NHL cells... Taken together, FASN oncogenic activity appears to extend beyond de novo fatty acid biosynthesis, serving as a central onco-metabolic regulator of malignant cell proliferation vis-à-vis integrating glucose, nucleotides, and antioxidant metabolic functions in NHL. In addition, co-targeting FASN and PI3K induced synergistic cell death. Altogether, blocking FASN and the dependent onco-metabolic functions represent highly novel targets for therapeutic strategies in NHL.
IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • FASN (Fatty acid synthase)
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buparlisib (AN2025) • cerulenin