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Journal Papers

At Sygnature Discovery we pride ourselves on being innovative and forward-thinking. We invest in the most cutting-edge technologies to deliver the best science that makes a difference to our clients.

Our commitment has successfully enabled the discovery and development of dozens of drug candidates that made it through to the clinic.

Our scientists have the expertise and the enthusiasm that often translates into novel and exciting scientific discoveries. Get up to date with our scientific breakthroughs by accessing our latest scientific publications.

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Fluorescent Thermal Shift Assays for Identifying Small Molecule Ligands

Andrew D. Scott Biophysical Techniques in Drug Discovery, Chapter 8, 2017, Pages 208-238. Fluorescent thermal shift assay (FTSA; also known as ThermoFluor, differential scanning fluorimetry (DSF), thermal shift assay (TSA) and temperature-dependent fluorescence (TdF))...

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Evaluation of the Biological Activity of Compounds: Techniques and Mechanism of Action Studies

Dougall, IC,  Unitt, J. The Practice of Medicinal Chemistry (Fourth Edition), Chapter 2, 2015, Pages 15–43. The first step in the biological assessment of compounds synthesized by medicinal chemists usually involves testing in a range of in vitro biochemical/pharmacological...

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Tools, techniques, organisation and culture of the CADD group at Sygnature Discovery

St-Gallay SA, Sambrook-Smith CP. J Comput Aided Mol Des. 2017 Mar;31(3):305-308. Computer-aided drug design encompasses a wide variety of tools and techniques, and can be implemented with a range of organisational structures and focus in different...

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FKBP5 mRNA Expression is a Biomarker for GR Antagonism

Bali, U., Phillips, T., Hunt, H., and Unitt, J. J Clin Endocrinol Metab. 2016 Nov;101(11):4305-4312 Context: Endogenous Cushing’s syndrome is caused by chronically elevated levels of cortisol. Mifepristone, a Glucocorticoid Receptor (GR) antagonist, is approved for the...

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Surface Plasmon Resonance for Identifying and Characterising Small Molecule Ligands

From the book “Biophysical Techniques in Drug Discovery”, Chapter 7, Pages 170 – 207 Editor: Angeles Canales S. J. Pollack Abstract Surface plasmon resonance (SPR) is a powerful technology that allows an information-rich assessment of the...

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Thermal Shift as an Entropy Driven Effect

Redhead M, Satchell R, McCarthy C, Pollack S, Unitt J. Biochemistry. 2017 Nov 28;56(47):6187-6199 Abstract Thermal shift assays (TSAs) are among the most commonly used biophysical approaches in drug discovery in both academic and...

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The Identification of the Clinical Candidate (R)-(1-(4-fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1Hpyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone (CORT125134):– A Selective Glucocorticoid Receptor (GR) Antagonist

Hunt HJ, Belanoff JK, Walters I, Gourdet B, Thomas J, Barton N, Unitt J, Phillips T, Swift D, Eaton E. J Med Chem. 2017 Apr 27;60(8):3405-3421 Abstract The nonselective glucocorticoid receptor (GR) antagonist mifepristone...

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1H-Pyrazolo[3,4-g]hexahydro-isoquinolines as potent GR antagonists with reduced hERG inhibition and an improved pharmacokinetic profile

Hunt HJ, Belanoff JK, Golding E, Gourdet B, Phillips T, Swift D, Thomas J, Unitt JF, Walters I. Bioorg Med Chem Lett. 2015 Dec 15;25(24):5720-5 Abstract We report the further optimization of our series 1H-pyrazolohexahydro-isoquinoline...

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A combinatorial biophysical approach; FTSA and SPR for identifying small molecule ligands and PAINs

Redhead M, Satchell R, Morkūnaitė V, Swift D, Petrauskas V, Golding E, Onions S, Matulis D, Unitt J. Anal Biochem. 2015 Jun 15;479:63-73 Abstract Biophysical methods have emerged as attractive screening techniques in drug discovery both as primary hit finding methodologies, as in...

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