Technical Notes

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...

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...

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...

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....

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...

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...

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...

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...

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...

Metabolite Profiling and Identification

It is important to understand the routes of metabolism for compounds in drug discovery in order to design more metabolically stable drug candidates and to be aware of any potentially toxic metabolites that could...

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...

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...