Mitochondrial Liabilities Assay and Metabolism with ICDD

Sci Update

Several recent papers have highlighted the importance of identifying mitochondrial liabilities to completely assess the toxicity potential of a drug (1-3).  Mechanisms by which drugs induce organ toxicity include the production of reactive metabolites (4).  Examples such as high-dose acetaminophen, which produces metabolites toxic to the mitochondria are found in the literature (5-8). 

Metabolites or cocktails of metabolites obtained through the Hepatochem technologies may act on one or several mitochondrial targets to induce mitochondrial impairment.  ROS production or reduced anti-oxidant defenses, perturbation of the bioenergetic balance, induction of permeability transition, depletion of mtDNA or reduced mitochondrial mass are some of the various targets that may induce mitochondrial dysfunction, loss of susceptible cell integrity & ultimately organ malfunctions and/or failure (7,9-12).  Using the MitoSafe line of functional bioassays developed by ICDD will demonstrate whether metabolites of your drugs induce mitochondrial liabilities in live-cell models.  Mitochondria toxicity is most readily expressed clinically by hepatic injury & cardio-toxicity, which can both be flagged through the study of your compounds and their metabolites with the MitoSafe bioassays.

Don’t hesitate to ask questions to our mitochondria experts:Contact@icdd-sas.com

1- Marroquin LD, Hynes J, Dykens JA, Jamieson JD, Will Y. Toxicol Sci. 2007 ;97(2):539-47.

2- Dykens JA, Will Y. Drug Discov Today. 2007 ;12(17-18):777-85.

3- Begriche K, Massart J, Robin MA, Borgne-Sanchez A, Fromenty B.  J Hepatol. 2011 ;54(4):773-94.

4- Liebler DC, Guengerich FP.  Nat Rev Drug Discov. 2005 ;4(5):410-20.

5- Kostrubsky SE, Strom SC, Ellis E, Nelson SD, Mutlib AE. Chem Res Toxicol. 2007 ;20(10):1503-12.

6- Jaeschke H, McGill MR, Williams CD, Ramachandran A.  Life Sci. 2011 25;88(17-18):737-45.

7- Song Y, Shi Y, Yu H, Hu Y, Wang Y, Yang K. Toxicol Lett. 2011 ;202(1):55-60.

8- Chaudhuri L, Sarsour EH, Goswami PC. Environ Int. 2010 ;36(8):924-30.

9- Siu WP, Pun PB, Latchoumycandane C, Boelsterli UA.  Toxicol Appl Pharmacol. 2008 ;227(3):451-61.

10- Bai J, Nakamura H, Ueda S, Kwon YW, Tanaka T, Ban S, Yodoi J. J Biol Chem. 2004 ;279(37):38710-4.

11- Ramachandran A, Lebofsky M, Weinman SA, Jaeschke H.Toxicol Appl Pharmacol. 2011 ;251(3):226-33.

12- Zou W, Roth RA, Younis HS, Burgoon LD, Ganey PE. Toxicology. 2010 ;272(1-3):32-8. 

Photochemistry

Hepatochem offers a variety of photochemistry reactors and accessories that are used throughout the world to explore chemical conditions. All of our reactors are compatible with most vial formats and stirring plates. We also offer several photochemistry screening kits for calibration and accuracy.

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The Biomimetic Advantage

While microsomes have proven valuable as a predictive tool, their productive capabilities are limited. Biomimetic Chemistry, on the other hand, possesses the advantages of both chemistry and biology and is thus a much more efficient tool for metabolite synthesis.

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Metabolite Synthesis

Through our revolutionary technology, HepatoChem enables cost effective testable quantities of metabolites in-house even at the earliest stages of drug discovery. This new capability, which enables affordable early metabolite toxicity testing, offers drug companies the opportunity to save millions each year through dramatically improved drug pipelines.