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In vitro tox assays for Medchem Support

Overview

Toxicity is the major cause of drug candidate failure in preclinical and clinical development stage, and also the major reason for the withdrawal of approved drugs from the market. While toxicity test has been traditionally completed in the preclinical phase, in vitro toxicity studies in the early drug discovery stages could significantly reduce failures at a later stage and prevent economic loss.

WuXi AppTec offers a panel of in vitro toxicity assays designed to identify compound toxicity in the early drug discovery stage. By utilizing cutting-edge technologies including conventional and automated patch clamp and high content screening (HCS), we provide the high-quality data quickly and cost-effectively. Applying these assays to your lead ID and optimization strategy helps to make a more thorough analysis of the severity and specificity of toxicity, then bto guide candidate compounds through the planning and execution of downstream in vivo toxicity and efficacy tests.

 

Cardiotoxicity

  • Cardiac ion channel safety panel (CIPA compliant) with manual and automated patch-clamp: including hERG, hCav1.2, hNav1.5 (early and late), hKCNQ1/mink, hKv4.3/KChIP2.2, hKir2.1 channels
  • Human stem cell derived cardiomyocytes cardiotoxicity testing with MEA

 

General Cytotoxicity

  • Cell viability Assay: CellTiter-Glo® (Promega) or HCS assay
  • Apoptosis assay
  • CellTox™ Green cytotoxicity assay (Promega)
  • ApoTox-Glo™ Triplex Assay (Promega)

 

Mitochondrial Toxicity

  • Mitochondrial Membrane Potential Assay
  • Mitochondrial Reactive Oxygen Species (ROS) Assay
  • MitoXpress® Xtra OCR Assay (HS method) (Luxcel)
  • MitoXpress® Cellular Energy Flux OCR/ECAR Assay from (Luxcel)
  • Glucose/Galactose Assay
  • MitoBiogenesis Assay

 

Lipotoxicity

  • Phospholipidosis and steatosis assays

 

Hepatotoxicity with HepG2 or Primary Human Liver Cell Culture

  • Selected general cytotoxicity and mitochondrial toxicity assays listed above

 

Nephrotoxicity with HK-2 Cells

  • Selected general cytotoxicity and mitochondrial toxicity assays listed above

 

Genotoxicity

  • Ames assay
  • In vitro micronucleus assay

 

Photo Toxicity

  • In vitro 3T3 NRU Phototoxicity test

 

Fig 1. A hERG current recorded on QPatch, B hiPSC-vCMs recording on MEA system.

 

Fig 2, Mitochondrial membrane potential assay using HepG2 cells.

 

Fig 3. Nephrotoxicity assay with HK-2 cells.  

 

Fig 4. In vitro 3T3 NRU phototoxicity test