Prodrug thiamine analogs as inhibitors of the enzyme transketolase

Huérou, Yvan Le; Gunawardana, Indrani; Thomas, Allen A.; Boyd, Steven A.; Meese, J. De; DeWolf, Walter E.; Gonzales, Steven S.; Han, May; Hayter, Laura; Kaplan, Tomas; Lemieux, Christine L.; Lee, Patrice; Pheneger, Jed; Pöch, G; Romoff, Todd T.; Sullivan, Francis X.; Weiler, Solly; Wright, S. Kirk; Lin, Jie

doi:10.1016/j.bmcl.2007.11.100

Cited by 23 publications

(23 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, we detected a significant effect of oxythiamine only in one of the thyroid cancer cell lines indicating that oxythiamine may not be effective in most differentiated thyroid carcinoma. Recently, more new thiamine analogs as more specific inhibitors have been developed [31]. Future experiments will show if they have higher efficacy in TKTL-1 expressing tumor cell lines than oxythiamine.…”

Section: Discussionmentioning

confidence: 98%

Is transketolase like 1 a target for the treatment of differentiated thyroid carcinoma? A study on thyroid cancer cell lines

Frőhlich¹,

Fink²,

Wahl³

2008

Invest New Drugs

View full text Add to dashboard Cite

Radioactive iodine-refractory [(18)F] fluorodeoxy-glucose-positron emission tomography-positive thyroid carcinomas represent especially aggressive tumors. Targeting glucose metabolism by the transketolase isoenzyme transketolase like 1 (TKTL-1) which is over-expressed in various neoplasms, may be effective. The correlation of TKTL-1 expression and the response to oxythiamine as the currently best-characterized inhibitor of transketolases was studied in differentiated thyroid cancer cell lines. We determined TKTL-1 expression, proliferation, glucose uptake and GLUT-1 expression in non-treated thyroid cells and recorded the effect of oxythiamine on iodide uptake and on thymidine uptake. TKTL 1 was highest expressed in cell lines derived from more invasive tumors but the expression level was not strongly correlated to proliferation rate, to GLUT-1 expression or to the response to oxythiamine. Oxythiamine showed only a weak effect in the TKTL-1 expressing cell lines. Over-expression of TKTL-1 is not an indicator for responsiveness to oxythiamine. More specific inhibitors should be tested.

show abstract

Section: Discussionmentioning

confidence: 98%

Is transketolase like 1 a target for the treatment of differentiated thyroid carcinoma? A study on thyroid cancer cell lines

Frőhlich¹,

Fink²,

Wahl³

2008

Invest New Drugs

View full text Add to dashboard Cite

show abstract

“…As mentioned in the introduction, there is a growing interest in the search for specific TK inhibitors, particularly in anticancer field (Bentz et al, 2013;Du et al, 2004;Kochetov et al, 1971;Le Huerou et al, 2008;Nilsson et al, 1993;Obiol-Pardo et al, 2012;Raïs et al, 1999;Solovjeva and Kochetov 1999;Sprenger et al, 1995;Thomas et al, 2008aThomas et al, , 2008b. In this context, the emergence of rapid and inexpensive bioassays dedicated to TK activity detection in the presence of cofactor or substrate analogs is of importance.…”

Section: Detection Of Tk Inhibitorsmentioning

confidence: 97%

“…The most representative inhibitors that mimic the interactions with ThDP are oxythiamine (Raïs et al, 1999) and thiamine thiazolone diphosphate (Nilsson et al, 1993). More recently, in the aim of obtaining more selective TK inhibitors several thiamine antagonists (Le Huerou et al, 2008;Thomas et al, 2008aThomas et al, , 2008b and also a novel family of compounds based on critical allosteric points of enzyme were designed (Obiol-Pardo et al, 2012). The bienzymatic biosensor based on TK-GAOx proposed in this paper may enable a sensitive and generic detection of TK inhibitors by the decrease of oxidation current of enzymatic generated hydrogen peroxide.…”

Section: Introductionmentioning

confidence: 98%

An efficient amperometric transketolase assay: Towards inhibitor screening

Touisni

Charmantray

Hélaine

et al. 2014

Biosensors and Bioelectronics

View full text Add to dashboard Cite

“…Oxythiamine can also significantly inhibit the proliferation of metastatic ovarian cancer cells [106], and the combination of oxythiamine with DHEA shows better effects on impairing cancer cell growth [107]. An analog of thiamine, 5a ['N3'-pyridyl thiamine'; 3-(6-methyl-2-amino-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-4-methylthiazol-3-ium chloride hydrochloride] can also inhibit TKT [108] and ring-opened analogs of 5a improve its pharmacokinetic profile and show better effect in vivo [109]. Consequently, a bienzymatic biosensor was designed to screen various human TKT inhibitors [110].…”

Section: Targeting Anabolic Processmentioning

confidence: 99%

The greedy nature of mutant RAS: a boon for drug discovery targeting cancer metabolism?

Lv¹,

Wang²,

Chang³

et al. 2016

ABBS

View full text Add to dashboard Cite

RAS oncogene mutations are frequently detected in human cancers. Among RAS-mediated tumorigenesis, KRAS-driven cancers are the most frequently diagnosed and resistant to current therapies. Despite more than three decades of intensive efforts, there are still no specific therapies for mutant RAS proteins. While trying to block those well-established downstream pathways, such as the RAF-MAPK pathway and the PI3K-AKT pathway, attentions have been paid to potential effects of RAS on metabolic pathways and the feasibility for targeting these pathways. Recent studies have proved that RAS not only promotes aerobic glycolysis and glutamine metabolism reprograming to provide energy, but it also facilitates branched metabolism pathways, autophagy, and macropinocytosis. These alterations generate building blocks for tumor growth and strengthen antioxidant defense in tumor cells. All of these metabolic changes meet different demands of RAS-driven cancers, making them distinct from normal cells. Indeed, some achievements have been made to inhibit tumor growth through targeting specific metabolism rewiring in preclinical models. Although there is still a long way to elucidate the landscape of altered metabolism, we believe that specific metabolic enzymes or pathways could be therapeutically targeted for selective inhibition of RAS-driven cancers.

show abstract

Prodrug thiamine analogs as inhibitors of the enzyme transketolase

Cited by 23 publications

References 23 publications

Is transketolase like 1 a target for the treatment of differentiated thyroid carcinoma? A study on thyroid cancer cell lines

Is transketolase like 1 a target for the treatment of differentiated thyroid carcinoma? A study on thyroid cancer cell lines

An efficient amperometric transketolase assay: Towards inhibitor screening

The greedy nature of mutant RAS: a boon for drug discovery targeting cancer metabolism?

Contact Info

Product

Resources

About