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Intracellular Signalling

Intracellular signalling is an integral means by which cells can finely regulate and maintain their function in response to stimuli in their environment, and hence are a prime target for drug design. To complement our breadth of Computational and Medicinal Chemistry expertise, in the targeting of receptors for the development of novel therapeutics, our bioscience team have developed a variety of binding, signalling, and functional assays to evaluate receptor affinity and Mechanism of Action (MOA) of the ligand of interest.

A large proportion of signalling cascades begin where ligands interact at the cell surface with membrane-associated receptors, which include ion channels, G Protein-Coupled Receptors (GPCRs) and Receptors Tyrosine Kinase (RTKs). The transduction and amplification of these signals through a plethora of complex pathways leads to control of signal mediators such as enzymes, cofactors, and transcription factors that in turn modulate essential downstream cellular functions. Sygnature’s bioscientists have experience in performing a number of assays using a variety of highly sensitive technology platforms to quantify intracellular messengers such as, intracellular Ca2+ mobilisation, inositol monophosphate (IP1), and cyclic AMP (cAMP), as well as phosphoproteins. Our intracellular signalling assays, in addition to tailor-made assays measuring Phosphoprotein and Cytokine Levels, are able to provide a full profile assessment of a drug candidate’s influence on cellular signalling pathways.  This is prosecuted using techniques including and not limited to High content image , Western Blotting and Luminex etc.

Example data showing the pharmacology of three test H1 Receptor antagonist (Mepyramine) concentrations within H1 receptor-expressing HeLa cells in comparison to a histamine agonist control. Data are expressed as % increase in calcium ions (Ca2+).

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