Glutathione (GSH) Trapping Assay
Drug metabolism can generate chemically reactive metabolites which have the potential to react with cellular components, such as DNA and proteins, altering their function and risk inducing idiosyncratic toxicity. This is a major issue...
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Cyanide Trapping Assay
Drug metabolism can generate chemically reactive metabolites which have the potential to react with cellular components, such as DNA and proteins, altering their function and risk inducing idiosyncratic toxicity. This is a major issue...
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Mitochondrial Toxicity Glu/Gal Assay (MitoTox Glo)
Mitochondrial dysfunction due to drug-induced effects, has been highlighted as a potential contributor to a number of organ toxicities including those associated with cardiac, muscular and liver systems (1). Mitochondrial toxicity has been indicated...
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Steatosis
Steatosis describes increased accumulation of lipids, mainly triglycerides, in the liver and can be induced by a number of factors including pre-existing conditions, pregnancy and exposure to certain xenobiotics1. These events are usually present...
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Parallel Artificial Membrane Permeability Assay (PAMPA)
Permeability is an important physicochemical property of a drug, governing the availability of the drug in the systematic circulation. PAMPA measures passive diffusion and is therefore the first port of call when looking into...
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Phospholipidosis
Drug-induced phospholipidosis (PLD) is an adverse drug reaction characterised by the intracellular accumulation of phospholipids and the appearance of cytosolic lamellar bodies. It is recognised by the pharmaceutical industry and regulatory bodies as a...
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UGT1A1/UGT1A3 Inhibition Assay
Uridine 5’-diphospho‐glucuronosyltransferases (UGTs) are a superfamily of enzymes which catalyse the glucuronidation reaction, a major phase II metabolism pathway. Approximately 15% of approved drugs have glucuronide metabolites1, highlighting the importance of UGT enzymes. UGT...
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Mitochondrial Toxicity in Glu/Gal HepG2 Model
Mitochondrial dysfunction due to drug-induced effects, has been highlighted as a potential contributor to a number of organ toxicities including those associated with cardiac, muscular and liver systems (1). Mitochondrial toxicity has been indicated...
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OATP1B1 and OATP1B3 inhibition
OATP1B1/OATP1B3 (Organic Anion Transporter Protein B1 and B3) are uptake transporters involved in the transport and disposition of endogenous and exogenous compounds. Expressed exclusively on the sinusoidal side of hepatocytes, these transporters are responsible...
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NTCP (Na+-Taurocholate Cotransporting Polypeptide)
The Na+-Taurocholate Cotransporting Polypeptide (NTCP) transporter is involved in the disposition and recirculation of bile acids; bile salts secreted into the bile are often re-absorbed into the portal circulation and back into the liver via...
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Aldehyde Oxidase (AO) Reaction Phenotyping
Aldehyde Oxidase is a homo-dimeric molybdo-flavo protein located in the cytosolic fraction of various tissues (e.g. brain, kidney, lung, GIT) and species, but is predominantly expressed in liver. The enzyme shows activity differences across...
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Metabolic Stability of Low Clearance Compounds
Sygnature’s routine hepatocyte stability assay monitors the disappearance of a substrate in suspension, over 1-2 hours incubation. Evaluating low clearance compounds can be a challenge using existing methods. To accurately determine intrinsic clearance and...
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Cytochrome P450 Inhibition (Time dependent IC50 shift)
The cytochrome P450 (CYP450) enzymes play a significant role in the metabolism of both endogenous and exogenous compounds. Within this family, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 are predominantly involved in the...
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Thermodynamic Solubility
Low solubility can be a major obstacle during drug discovery and development, as low solubility can impact the generation of quality in vitro DMPK or biology data, can cause issues in the generation of...
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MDCK-WT/MDR1 Permeability
Wild-type MDCK (Madin-Darby canine kidney) cells, when transfected with either the Multidrug Resistance gene-1 (MDR1; P-gp) or Breast Cancer Resistance gene (BCRP), are used as a model of brain penetration and to understand the...
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BSEP inhibition
The bile salt export pump, BSEP (ABCB11), is located at the canalicular (apical) membrane of hepatocytes and is involved in the secretion of bilirubin/bile salts from the liver. Since bile formation and secretion are...
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Tubidimetric Solubility
Low solubility can be a major obstacle during drug discovery and development, as low solubility can impact the generation of quality in vitro DMPK or biology data, can cause issues in the generation of...
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Plasma Stability
The measurement of the stability of a new chemical entity in a matrix such as plasma helps in identifying and understanding the lability of known structural moieties (e.g. amides, sulphonamide, esters, lactones, lactams to...
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Plasma Protein Binding
Drugs may bind to a wide variety of plasma proteins, including albumin, and the degree of binding can impact on the pharmacokinetics and pharmacodynamics parameters of a drug, given that only the free drug...
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MRP2 Inhibition
Multidrug resistant associated protein 2 (MRP2; ABCC2) is member of a family of ATP-binding cassette drug efflux transporters located in the cannalicular (apical) membrane of hepatocytes. Loss of function mutations of this transporter have...
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Microsomal Metabolic Stability
The liver is the major site of drug metabolism in the body, with well over 50% of marketed drugs being eliminated via hepatic mediated metabolism. Hence, measurement of the rate of clearance and the...
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Microsomal Protein Binding
Understanding the non-specific binding of drugs to microsomal protein and fuinc is beneficial in generating an accurate prediction of in vivo clearance and drug-drug interactions. The leading approach for assessing microsomal protein binding is...
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LogD (Micro Shake-Flask)
Lipophilicity (distribution coefficient) is an important physicochemical property of a drug as it provides an understanding of how well a drug will cross lipid membranes (and thereby penetrate tissues), how well a drug will...
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Hepatocyte Metabolic Stability
The liver is the major site of drug metabolism in the body, with well over 50 % of marketed drugs are eliminated via hepatic mediated metabolism. Hence, measurement of the rate of clearance and...
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Cytochrome P450 Inhibition (Reversible)
The cytochrome P450 (CYP450) enzymes play a significant role in the metabolism of both endogenous and exogenous compounds. Within this family, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 are predominantly involved in the...
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Chemical Stability
The measurement of the stability of a drug in conditions that mimic the gastrointestinal tract, physiological conditions and/or in vitro biological conditions helps in identifying and understanding the lability of molecules due to non-enzymatic...
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Caco-2 Permeability
The human colon epithelial cancer cell line, Caco-2, is used as a model of human intestinal absorption of drugs. This model is suitable to test compound suitability for oral dosing, predict intestinal permeability and...
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Cell Viability Assessment
Cell viability or cytotoxicity assessments are based on cellular functions that are particularly sensitive to toxic drugs and as such provide convenient in vitro high-throughput screens (HTS) for comparing relative toxicities of a drug....
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