Life Sciences Focus: Drug Discovery
m ‘Drugging the undruggable’: identifying new drug targets
Through the application of its SITESEEKER drug target identification platform and working on collaboration with pharma and biopharma companies, UK-based PhoreMost is expanding the druggable space to develop next- generation therapeutics.
hroughout the year, UK- based biopharmaceutical company PhoreMost Limited has been entering into drug
discovery collaborations with other pharma and biopharma companies designed to expand the druggable space. For example, in September, the company established a drug discovery collaboration agreement with algorithm-driven artificial intelligence (AI)-based pharmaceutical technology company XtalPi Inc in which the two companies will aim to rapidly identify and develop compounds to advance a drug discovery programme against targets that epigenetically regulate tumour progression. These targets have been previously classified as ‘undruggable’ and PhoreMost and XtalPi will pursue this goal with their combination of machine learning and physics-based computation methods using XtalPi’s intelligent digital drug discovery and development (ID4) platform to explore novel sites discovered by PhoreMost’s SITESEEKER platform.
How the ‘undruggable’ becomes ‘druggable’ SITESEEKER exploits protein shape diversity to find new peptide targets, significantly enhancing
PhoreMost’s drug discovery technology goes beyond conventional methods used in the discovery of new drug targets as these conventional technologies are often unable to detect biological targets or fail to identify suitable drug candidates for these targets. The company’s novel SITESEEKER platform rapidly identifies ‘cryptic’ druggable sites using protein interference (PROTEINi) libraries exploiting the
At the beginning of the year, PhoreMost entered into a multi- project drug discovery collaboration with Otsuka Pharmaceutical in which the company is deploying SITESEEKER towards disease- relevant pathways nominated by Otsuka.
Protein-protein interaction sites are traditionally considered ’undruggable’ by small-molecules due to their large flat surface and the absence of well-defined binding pockets. XtalPi’s ID4 platform integrates data-driven AI models with physics-based methods to quickly distil a small number of high-quality compounds from an AI-generated target-specific chemical space that includes millions of diverse molecules. Such diversity, combined with ID4’s drug property prediction algorithms’ speed and accuracy, allows the discovery of promising candidates, thus overcoming the bottleneck of simultaneously optimizing all pharmacological properties and ensuring a smooth progression into preclinical and clinical studies.
the power of phenotypic screening and translation into therapeutic modalities. Based on proprietary protein interference (PROTEINi) technology, PhoreMost uses SITESEEKER to probe the entire proteome in a live cell environment for novel druggable targets linked to any chosen disease. This enables the systematic discovery of functionally active peptides that are directly linked to useful therapeutic applications.
shape and diversity inherent in proteins in order to identify these new drug targets.
PROTEINi libraries are very large collections of shapes that can find new target-interaction sites throughout the whole proteome. They utilize diverse libraries of small, self-folding, three- dimensional peptide ‘shapes’ expressed in live cells, which, in a similar manner to small molecules, interact with available
Pharma partners: Otsuka Pharmaceutical and Boehringer-Ingelheim At the beginning of the year, PhoreMost entered into a multi- project drug discovery collaboration with Otsuka Pharmaceutical in which the company is deploying SITESEEKER towards disease- relevant pathways nominated by Otsuka. Novel targets identified in the collaboration are being further validated and characterized
pockets on target proteins on a proteome-wide scale. Pooled phenotypic screening formats are used to rapidly identify peptide- target interactions of therapeutic interest, these then being used as a starting point in the design of small-molecule inhibitors. PROTEINi are small protein fragments that are themselves broken down into smaller subunits while retaining a 3D structure that can bind with a range of new 3D
by Otsuka as part of its internal development pipeline, with an initial focus on gene therapy applications of identified targets. Dr Chris Torrance, CEO of PhoreMost says the collaboration with Otsuka is further recognition of the power of the SITESEEKER approach to drive the identification of novel, druggable targets and that the company is particularly pleased to be exploring not only small- molecule therapeutics but also gene therapy applications of its platform.
Also early in 2020, PhoreMost entered into a multi-project drug discovery collaboration with Boehringer Ingelheim in the field of developing innovative therapies for diseases with unsatisfactory treatments in which PhoreMost is using SITESEEKER in investigating disease-relevant pathways nominated by Boehringer Ingelheim. Novel targets identified are being validated and characterized by Boehringer Ingelheim as part of its internal discovery research pipeline within the fields of immunology and respiratory diseases, cardiometabolic diseases, oncology research and immuno- oncology, as well as diseases of the central nervous system.
New drug discovery technology: how SITESEEKER and PROTEINi work
binding sites across the whole proteome. This binding occurs in a live-cell phenotypic setting to give a useful disease readout that can be directly and simultaneously defined and thus find a new way of ‘drugging the undruggable’.
Further information PhoreMost Limited Ph: +44 (0)1223 804161 E: firstname.lastname@example.org
m W: www.phoremost.co
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Autumn 2020 April/May 2020
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