Farnesyl-Diphosphate Farnesyltransferase (Squalene Synthase)

The first committed enzyme of the biosynthesis pathway that leads to the production of STEROLS. it catalyzes the synthesis of SQUALENE from farnesyl pyrophosphate via the intermediate PRESQUALENE PYROPHOSPHATE. This enzyme is also a critical branch point enzyme in the biosynthesis of ISOPRENOIDS that is thought to regulate the flux of isoprene intermediates through the sterol pathway.

Also Known As:

Squalene Synthase; Squalene Synthetase; FPP-FPP Farnesyl Transferase; Farnesyldiphosphate-Farnesyldiphosphate Farnesyltransferase; Presqualene-Diphosphate Synthase; FPP FPP Farnesyl Transferase; Farnesyl Diphosphate Farnesyltransferase; Farnesyl Transferase, FPP-FPP; Farnesyldiphosphate Farnesyldiphosphate Farnesyltransferase; Farnesyltransferase, Farnesyl-Diphosphate; Farnesyltransferase, Farnesyldiphosphate-Farnesyldiphosphate; Presqualene Diphosphate Synthase; Synthase, Presqualene-Diphosphate; Synthase, Squalene; Synthetase, Squalene; Transferase, FPP-FPP Farnesyl

Networked: 76 relevant articles (1 outcomes, 6 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Enzymes and Coenzymes: 1
- Enzymes: 152586
  - Transferases: 6589
    - Alkyl and Aryl Transferases: 180
      - Farnesyl-Diphosphate Farnesyltransferase: 76
        S cerevisiae ERG9 protein
        Staphylococcus aureus CrtM protein

Experts

1.	Kourounakis, Angeliki P: 4 articles (09/2017 - 12/2007)
2.	Matralis, Alexios N: 3 articles (09/2017 - 11/2010)
3.	Urbina, Julio A: 3 articles (05/2014 - 12/2005)
4.	de Souza, Wanderley: 3 articles (05/2014 - 12/2005)
5.	Chen, Chun-Chi: 2 articles (07/2022 - 05/2014)
6.	Guo, Rey-Ting: 2 articles (07/2022 - 05/2014)
7.	Oldfield, Eric: 2 articles (07/2022 - 05/2014)
8.	Shang, Na: 2 articles (07/2022 - 05/2014)
9.	Chang, Yu-Chan: 2 articles (08/2020 - 09/2014)
10.	Hsiao, Michael: 2 articles (08/2020 - 09/2014)

Related Diseases

1.	Myotoxicity 07/01/1997 - "Inhibition of cholesterol synthesis by squalene synthase inhibitors does not induce myotoxicity in vitro." 11/01/2004 - "Zaragozic acid A, a squalene synthase inhibitor, caused no apoptosis on its own and had no effect on Compound-A-induced myotoxicity, suggesting the apoptosis was not a result of cholesterol synthesis inhibition. " 08/15/2007 - "Protective effects of a squalene synthase inhibitor, lapaquistat acetate (TAK-475), on statin-induced myotoxicity in guinea pigs."
2.	Neoplasms (Cancer) 07/01/2016 - "In this work, we studied the effect of Matricaria recutita extract on ERG9 gene (squalene synthase) expression in S.cerevisiae which was used as organism model in cancer therapy. " 03/01/2022 - "Squalene synthase accelerated colon cancer cell proliferation and promoted tumor growth. " 03/01/2022 - "Squalene synthase was significantly upregulated in stage I-III COAD and positively correlated with poor differentiation and advanced tumor stage. " 09/15/2014 - "Squalene synthase (SQS) was up-regulated in CL1-5 cells and in the tumor regions of the lung cancer specimens. " 06/29/2007 - "Squalene synthase, a determinant of Raft-associated cholesterol and modulator of cancer cell proliferation."
3.	Hepatocellular Carcinoma (Hepatoma) 06/05/1992 - "Subcellular localization of squalene synthase in human hepatoma cell line Hep G2." 01/01/2018 - "The best scoring molecule, compound 67 showed 53% inhibition of the human Squalene synthase enzyme, isolated from the cell lysates of Human Hepatoma Cell Line, at a dose of 10 mcg with an IC50 value of 9.43 µm." 08/15/2003 - "Among the novel compounds, (Z)-2-[2-(quinuclidin-3-ylidene)ethoxy]-9H-carbazole hydrochloride 8 (YM-53579) and (E)-2-[2-fluoro-2-(quinuclidin-3-ylidene)ethoxy]-9H-carbazole hydrochloride 28 (YM-53601) were potent inhibitors of squalene synthase derived from human hepatoma cells, with IC(50) values of 160 and 79 nM, respectively. " 05/29/2003 - "Among these compounds, (Z)-3-[2-(9H-fluoren-2-yloxy)ethylidene]-quinuclidine hydrochloride 31 was found to be a potent inhibitor of squalene synthase derived from hamster liver and human hepatoma cells with IC(50) values of 76 and 48 nM, respectively. " 02/22/2002 - "Squalestatin1 (SQ1), a potent inhibitor of squalene synthase produced a dose-dependent induction of cytochromes P450 CYP2H1 and CYP3A37 mRNAs in chicken hepatoma cells. "
4.	Inflammation (Inflammations) 01/01/2021 - "Mevalonate Kinase Deficiency and Squalene Synthase Inhibitor (TAK-475): The Balance to Extinguish the Inflammation." 08/01/1997 - "Taken together, our results suggest that the discordant regulation of HMG-CoA reductase and squalene synthase during the host response to infection and inflammation may have substantial effects on the regulation of substrate flux into the non-sterol pathways of mevalonate metabolism." 11/01/2004 - "This article summarises novel developments in the lipid-altering therapies under development, including combination therapies, squalene synthase inhibitors, microsomal transfer protein inhibitors, acyl-cholesterol acyl transferase inhibitors, cholesterol ester transfer protein antagonists, peroxisome proliferator-activated receptor agonists, high-density lipoprotein-derived peptides and inflammation inhibitors, which have at least reached trials in animal models. "
5.	Mycoses (Diseases, Fungus) 07/05/2022 - "There is interest in the development of drugs to treat fungal infections due to the increasing threat of drug resistance, and here, we report the first crystallographic structure of the catalytic domain of a fungal squalene synthase (SQS), Aspergillus flavus SQS (AfSQS), a potential drug target, together with a bioinformatics study of fungal, human, and protozoal SQSs. " 01/21/2011 - "The antifungal drugs most widely used to treated fungal infections are compounds that inhibit cytochrome P450-dependent C14α-demethylase (CYP51), but other enzymes of this pathway, such as squalene synthase (SQS) which catalyses the first committed step in sterol biosynthesis, could be viable targets. "

Related Drugs and Biologics

1.	1- ((1- (3- acetoxy- 2,2- dimethylpropyl)- 7- chloro- 5- (2,3- dimethoxyphenyl)- 2- oxo- 1,2,3,5- tetrahydro- 4,1- benzoxazepin- 3- yl)acetyl)piperidine- 4- acetic acid
2.	Acetates (Acetic Acid Esters)
3.	Hydroxymethylglutaryl-CoA Reductase Inhibitors (HMG-CoA Reductase Inhibitors)
4.	Cholesterol
5.	Enzymes
6.	Proteins (Proteins, Gene)
7.	Lipids
8.	Hydroxymethylglutaryl CoA Reductases (HMG CoA Reductase)
9.	Peroxisome Proliferator-Activated Receptors (PPAR)
10.	Untranslated RNA (Noncoding RNA)

Related Therapies and Procedures

1.	Therapeutics
2.	Lenses
3.	Drug Therapy (Chemotherapy)