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Technical Notes

Search and find out about most of our fully developed and validated DMPK, Physical Sciences and Discovery Toxicology assays by accessing our technical notes.

Wherever possible, and for the most standardised assays, we provide a full description of the assay, specifications, requirements and deliverables.

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Acute feeding studies

Acute feeding studies  provide an excellent screening platform to quickly understand the hypophagic potential of a novel drug. These assays are typically performed in  lean mice or rats but can also be performed in...

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Adriamycin-induced model of focal segmental glomerulosclerosis (FSGS) and fibrosis

Focal segmental glomerulosclerosis (FSGS) is one of the most common causes of primary glomerular diseases in adults. FSGS is induced in rodents by administration of adriamycin (anthracycline also called doxorubicin).  Structural and functional injury...

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Anti-GBM Model of nephrotoxic nephritis and inflammation

Glomerulonephritis (GN) is a group of diseases involving damage to the glomeruli caused by inflammation. We have developed the antibody induced anti-GBM (glomerular basement membrane) rodent model of glomerulonephritis that mimics human GN by rapid...

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Aqueous solubility – turbidimetric / kinetic – thermodynamic

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 an appropriate...

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Assessment of energy expenditure

The mechanisms underlying the reduction in body weight produced by novel anti-obesity drugs should always be investigated by measuring the effects of the compound on both sides of the energy equation balance.   We...

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Assessment of gastric emptying rate to explore mechanisms of satiety and reduced food intake

The inhibition of gastric emptying has been linked to satiety and reduced food intake. We offer direct (phenol red recovery) and indirect (serum APAP) models of gastric emptying, depending on your project requirements. This...

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Behavioural aspects of feeding to explore specificity of effects on food intake

When a drug reduces gross food intake following acute administration, several different studies can be performed to confirm that it is acting specifically on the mechanisms controlling food intake, rather than producing non-specific behavioural...

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Binge Eating Disorder

Sygnature has successfully developed and validated a new rat model of binge-eating disorder. Rats are given free access to normal rat diet and irregular access to chocolate for limited periods (2 h). After 3-4...

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Blood Plasma Partitioning

Certain drugs are highly bound to red blood cells (RBC) whilst others are highly bound to plasma proteins. As pharmacokinetics are mostly measured from plasma samples, binding to RBC can lead to dramatically miscalculated...

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Body composition analysis to determine specificity of weight loss

Body composition analysis can be used to investigate whether weight loss is accounted for by a clinically beneficial selective loss of fat, or by producing non-specific decreases in water (dehydration) and/or protein content (muscle...

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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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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 processes. High...

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CYP Induction (mRNA) / HepaRG

Cytochrome P450 (CYP) induction by a drug can accelerate the metabolism of a co-administered victim drug significantly, causing serious drug-drug interactions. To date induction of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4 have been...

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Cytotoxicity testing

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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Dietary-induced obese (DIO) mice and rats

Dietary-induced obese (DIO) mice and rats are well-established animal models of obesity that offer proven predictive validity of clinically effective weight loss drugs. Our DIO mouse model is ready to use, therefore enabling a...

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Drug Discrimination

Most CNS drugs produce a pharmacologically specific interoceptive cue in rats that they can use to differentiate between the training drug and vehicle. Drug discrimination testing using abused drugs as the training cues is...

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Early assessment of abuse potential.

Sygnature offers a range of models that can be used to explore the pharmacological profiles of novel drugs compared to known drugs of abuse, allowing the early assessment of abuse potential. Locomotor activity All...

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Genetic models of insulin resistance and type 2 diabetes

We have extensive experience  of working with animal models that are genetically predisposed to developing insulin resistance and progressive type 2 diabetes. Depending on the therapeutic indication, for example, insulin resistance or overt diabetes,...

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Glucocorticoid-induced model of insulin resistance

We have developed a rapid model of insulin resistance induced by sub-chronic administration of the glucocorticoid, cortisone, resulting in significantly increased plasma glucose and insulin levels within 7 days in rats. This model can be used...

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Glucose and insulin tolerance testing

Glucose tolerance testing via a variety of routes, i.e. OGTT, ipGTT, ivGTT) in mice and rats is a measure of how efficiently an exogenously delivered glucose load is cleared from the blood. Moreover, the...

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H-FFC CCl4 model of severe fibrosis and NASH

Non-alcoholic fatty liver disease (NAFLD) is a complex spectrum of liver diseases ranging from simple hepatic steatosis through to non-alcoholic steatohepatitis (NASH) which can ultimately lead to end-stage liver disease. Patients with NASH who...

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H-FFC mouse model of NASH and fibrosis

Non-alcoholic steatohepatitis (NASH) and liver fibrosis are associated with an increased risk of developing hepatocellular carcinoma and ultimately end-stage liver disease. In the clinic NASH is often accompanied with metabolic syndrome, specifically obesity, type...

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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 eliminated via hepatic mediated metabolism. Hence, measurement of the rate of clearance and the identity...

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In vivo PK / Pharmacokinetic studies

Pharmacokinetics describes the relationship between drug concentration and time in an organism following administration. Explicitly, pharmacokinetics is the study of drug absorption, distribution, metabolism and elimination (ADME). Typically, the first in vivo experiment during an oral...

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Intracerebral microdialysis

Sygnature is a leading provider of intracerebral microdialysis services in rats and mice. Our dedicated team of experts have been conducting microdialysis studies for more than 20 years and can design bespoke studies to...

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LogD (Micro Shake-Flask)

Highly lipophilic compounds (logD7.4 > 3.5) are likely to have: Poor aqueous solubility that can compromise intestinal absorption High first-pass metabolism, leading to high in vivo clearance and contributing to low oral bioavailability High binding...

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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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Metabolite Profiling

Although metabolism of drugs, or xenobiotics in general, occurs in a variety of tissues – such as the intestinal wall, lung, kidneys, skin and blood – the liver is regarded as the major site...

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Microsomal Clearance/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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P450 / CYP Inhibition

Inhibition of cytochrome P450 (CYP450) enzymes is one of the major reasons for drug-drug interactions (DDI), as they play a significant role in the metabolism of both endogenous and exogenous compounds. Therefore, detailed CYP...

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