Sosei Heptares group welcomes you to CHISHIKI, the destination for updates on our progress in the world of GPCRs. CHISHIKI is the Japanese word for “knowledge.” CHISHIKI is our online voice for communicating the scientific progress of our research and development activities, together with our broader contributions to the area of GPCRs.
Sosei Heptares presents latest methodological advances in AI applied to SBDD at 12th International Conference on Chemical Structures, the Netherlands
By Sosei Heptares Computational Chemistry Team | Aug 10, 2022
The International Conference on Chemical Structures (ICCS) takes place every three years at Noordwijkerhout (the Netherlands), bringing together experts in the field of cheminformatics (including AI/machine learning) from both academia and industry. Due to the pandemic, the 12th meeting (June 12-16 2022) took place after a four-year gap and thus it gave an opportunity for the community to come together after a long hiatus. Three representatives from Sosei Heptares presented their work this year: Mr Morgan Thomas, Ms Dominique Sydow and Dr Noel O’Boyle.READ MORE...
Discovery of HTL0039732: A Potent and Selective EP4 Receptor Antagonist for Cancer Immunotherapy
By Nigel Swain | Aug 7, 2022
Nigel Swain, a senior director in our Medicinal Chemistry department, recently presented at the 2022 Medicinal Chemistry Gordon Research Conference, showcasing rational design using Structure Based Drug Design (SBDD) and X-ray crystallography of the Sosei Heptares EP4 receptor antagonist preclinical candidate HTL0039732.READ MORE...
Modulation of Striatal Adenosinergic Function by HTL0041178, a Selective GPR52 Agonist
By Cliona MacSweeney | Apr 20, 2022
Cliona MacSweeney, a project director in our Translational Medicine department, recently presented this important pre-clinical work at SIRS2022 confirming the ability of the highly selective novel GPR52 agonist HTL00411718 to modulate centrally mediated locomotor activity in response to A2A receptor antagonists. This work highlights an important interplay between the adenosinergic and dopaminergic systems and suggests the potential for GPR52 agonists to control neuropsychiatric symptoms in conditions such as schizophrenia.READ MORE...
Targeting the M1 muscarinic receptor in neurodegenerative disease
By Sophie Bradley | Apr 12, 2022
Sophie Bradley, Translational Sciences Associate Director at Sosei Heptares, recently presented at the Keystone Symposia GPCR Conference, a summary of work performed both at Sosei Heptares and Glasgow University characterising the role of the muscarinic M1 receptor in cognitive and neurodegenerative disorders and the potential therapeutic benefit of muscarinic M1 selective ligands.READ MORE...
Identification and characterisation of a dual GLP-1/GLP-2 agonist peptide, HTL0030023 using structure based drug design
By Rie Suzuki | Mar 29, 2022
Rie Suzuki, Director Translational Sciences at Sosei Heptares presented a poster at the American Chemical Society (ACS) Spring 2022 meeting, describing the design strategy and pharmacodynamic evaluation of HTL0030023, a novel GLP-1/ GLP-2 agonist.READ MORE...
Identification and characterisation of a novel GLP-1 receptor antagonist peptide HTL0033097
By Alastair Brown | Mar 29, 2022
Alastair Brown, VP Translational Sciences at Sosei Heptares presented a poster at the American Chemical Society (ACS) Spring 2022 meeting, describing the design strategy and pharmacodynamic evaluation of HTL0033097, a novel selective GLP-1 antagonist.READ MORE...
Identification of Subtype Selective SST5 Receptor Agonist Peptide HTL0030310 using Structure-Based Drug Design
By Miles Congreve | Mar 29, 2022
Miles Congreve, CSO at Sosei Heptares presented a poster at the American Chemical Society (ACS) Spring 2022 meeting, describing the SBDD based identification of HTL0030310, a novel selective SST5 agonist.
How an AI drug discovery collaboration between Sosei Heptares and PharmEnable is accelerating complex science: generating new hit molecules against a difficult GPCR target
By Sosei Heptares and PharmEnable | Jan 25, 2022
Artificial Intelligence (AI) is becoming an increasingly important part of drug discovery – as demonstrated by the significant progress in the ongoing collaboration between Sosei Heptares and PharmEnable focused on a challenging peptidergic G protein-coupled receptor (GPCR) target associated with neurological disease. The collaboration brings together Sosei Heptares’ expertise in GPCRs with PharmEnable’s AI technology and has greatly accelerated the usual timelines for such a project. Matt Barnes, VP Drug Discovery at Sosei Heptares, and James Dale, Director of Drug Discovery at PharmEnable, tell us more.READ MORE...
From structure to clinic: Design of a M1 muscarinic acetylcholine receptor agonist with the potential for symptomatic treatment of Alzheimer’s disease
By Sosei Heptares | Nov 24, 2021
An extensive review in the prestigious journal Cell describes ground-breaking research – led by Sosei Heptares in collaboration with the University of Glasgow and others – that describes, for the first time, the process of designing a new molecule (HTL9936) to selectively target the muscarinic M1 receptor in the brain and demonstrating, through laboratory preclinical and human clinical studies, the potential of this approach to create superior new drugs to improve cognitive function in Alzheimer’s Disease patients, while minimizing side-effects associated with previous attempts to target the M1 receptor.
Sosei Heptares boosts Artificial Intelligence and Computer-Aided Drug Design capabilities focused on GPCR-targeted drug discovery with new partnered initiatives
By Sosei Heptares | Oct 20, 2021
Sosei Heptares has recently presented progress in the development of novel approaches in combining AI molecule generation and GPCR Structure-Based Drug Design (SBDD) and will be participating in new collaborative initiatives in training in AI and Computer-Aided Drug Discovery (CADD).READ MORE...
The Identification of GPR52 Agonist HTL0041178, a potential therapy for schizoaffective and related psychiatric disorders
By Steve Watson | Sep 22, 2021
Steve Watson, Medicinal Chemistry Director at Sosei Heptares, recently attended the 21st RSC/SCI Medicinal Chemistry Symposium and presented “The Identification of GPR52 Agonist HTL0041178: A potential therapy for schizoaffective & related disorders” – the first public disclosure of HTL0041178.READ MORE...
Decoding the activity of acetylcholine in memory formation and opportunities for drug discovery
By Sosei Heptares | Sep 16, 2021
A research collaboration between the University of Bristol’s Centre for Synaptic Plasticity and Sosei Heptares has identified specific drug targets within neural circuits in the brain that encode memories, paving the way for significant advances in the treatment of a broad spectrum of brain disorders.READ MORE...
Flattening the ‘valley of death’: New tools in the hunt for better preclinical R&D
By Paul Morgan | Feb 23, 2021
Paul Morgan, Vice President Preclinical Development at Sosei Heptares, was recently invited to be part of a panel of senior pharma executives to discuss key trends and challenges faced by the industry in preclinical R&D. The webinar, hosted by Endpoints News, will be broadcasted on February 23, 2021 at 2-3pm EST.READ MORE...
Small molecule AZD4635 inhibitor of A2AR signaling rescues immune cell function including CD103+ dendritic cells enhancing anti-tumor immunity
By Sosei Heptares | Jul 30, 2020
Our publication, jointly authored with AstraZeneca, titled “Small molecule AZD4635 inhibitor of A2AR signaling rescues immune cell function including CD103+ dendritic cells enhancing anti-tumor immunity” was accepted into the Journal for ImmunoTherapy of Cancer.READ MORE...
Accurate Prediction of GPCR Ligand Binding Affinity with Free Energy Perturbation
By Francesca Deflorian et al. | Jun 26, 2020
Francesca Deflorian, Senior Scientist II, Computational Chemistry, together with fellow scientists from Sosei Heptares, Janssen Pharmaceutica N. V., and Leiden University, recently published a paper in Journal of Chemical Information and Modeling. Alchemical relative binding free energy (RBFE) calculations were performed on two GPCR systems, the adenosine A2A and the orexin 2 receptors, investigating parameters and protocols to improve the accuracy of the predictions and emphasizing GPCR-specific features.READ MORE...
Structure-Based Drug Discovery of HTL22562: a CGRP Receptor Antagonist For Acute Treatment of Migraine
By Sarah Bucknell et al. | Jun 23, 2020
Sarah Bucknell, Senior Scientist II Chemistry, together with fellow scientists from Sosei Heptares and Teva Pharmaceuticals, recently published a paper in the Journal of Medicinal Chemistry, titled "Structure-Based Drug Discovery of N-((R)-3-(7-Methyl-1H-indazol-5-yl)-1-oxo-1-(((S)-1-oxo-3-(piperidin-4-yl)-1-(4-(pyridin-4-yl)piperazin-1-yl)propan-2-yl)amino)propan-2-yl)-2'-oxo-1',2'-dihydrospiro[piperidine-4,4'-pyrido[2,3-d][1,3]oxazine]-1-carboxamide (HTL22562): a Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist For Acute Treatment of Migraine".READ MORE...
Preclinical Pharmacodynamic and Pharmacokinetic Characterisation of HTL A a Selective GPR52 Agonist
By Clíona MacSweeney et al. | May 7, 2020
Clíona MacSweeney, Associate Director, Translational Sciences at Sosei Heptares, recently shared her poster describing the pharmacodynamic and pharmacokinetic characterisation of our novel GPR52 agonist on the Society of Biological Psychiatry 75th Anniversary Meeting website portal.READ MORE...
Discngine announces that Sosei Heptares will use its 3decision® software to create an unprecedented structural GPCR chemogenomics platform
By Chris de Graaf | Apr 6, 2020
Discngine, a software company specializing in developing applications for life sciences research, announced today that Sosei Heptares, an international biopharmaceutical group focused on G protein-coupled receptors (GPCRs), has selected its 3decision software to be part of an unprecedented structural GPCR chemogenomics platform.READ MORE...
Impact of GPCR Structures on Drug Discovery
By Miles Congreve, Chris de Graaf, Nigel Swain, Christopher Tate | Apr 6, 2020
Co-founder Christopher Tate and scientists from Sosei Heptares recently published a paper in Cell which reviews the state of the art of GPCR structural biology and how it correlates with launched GPCR drugs and agents in clinical trials.READ MORE...
Application of Sosei Heptares GPCR StaR® platform for Structure Based Drug Design & Hit Identification
By Mathew Leveridge et al. | Jan 28, 2020
Mathew Leveridge, Senior Scientist, Pharmacology, attended the SLAS (Society for Laboratory Automation and Screening) 2020 conference in San Diego on 25-29th Jan to present on Application of Sosei Heptares GPCR StaR® platform for Structure Based Drug Design & Hit Identification.READ MORE...
Comparison of orexin 1 and orexin 2 ligand binding modes using X-ray crystallography and computational analysis
By Mathieu Rappas et al. | Dec 22, 2019
Mathieu Rappas, Head of Protein Expression and Biochemistry at Sosei Heptares, together with fellow scientists, recently published a Featured Article titled “Comparison of orexin 1 and orexin 2 ligand binding modes using X-ray crystallography and computational analysis” in the renowned Journal of Medicinal Chemistry. In the paper he presents X-ray structures of the orexin receptors in complex with ten new antagonist ligands from diverse chemotypes and discusses how selectivity between OX1 and OX2 can be achieved.READ MORE...
Development of Histamine H4 Receptor Target Engagement Assays in Immune Cell Populations Involved in Atopic Dermatitis Pathophysiology
By Eugenia Sergeev et al. | Dec 18, 2019
Eugenia Sergeev, Research Scientist, Molecular Pharmacology, attended Pharmacology 2019 organised by the British Pharmacological Society held on 15-17 December in Edinburgh, UK to present on Development of Histamine H4 Receptor Target Engagement Assays in Immune Cell Populations Involved in Atopic Dermatitis Pathophysiology.READ MORE...
Pharmacological characterisation of the LPS challenge human whole blood assay demonstrates EP4 dominance as a target engagement marker
By Hannah Neale et al. | Dec 18, 2019
Hannah Neale, Scientist, Molecular Pharmacology, attended Pharmacology 2019 organised by the British Pharmacological Society held on 15-17 December in Edinburgh, UK to present on Pharmacological characterisation of the LPS challenge human whole blood assay demonstrates EP4 dominance as a target engagement marker.READ MORE...
Discovery of A2AR antagonist HTL1071/AZD4635 using SBDD
By Miles Congreve | Dec 13, 2019
Miles Congreve, Chief Scientific Officer at Sosei Heptares, recently attended the 24th Japanese Foundation for Cancer Research-International Symposium on Cancer Chemotherapy (JFCR-ISCC) named “New Drugs in Development in Japan, Europe and the USA” held in Tokyo, Japan on 11-12 Dec and presented on discovery of A2AR antagonist AZD4635 (HTL1071) using SBDD. The presentation was based on the one given previously in the New Approaches in Medicinal Chemistry symposium in Cambridge, UK on 20 June 2019.READ MORE...
Modulation of dopaminergic and glutamatergic function by GPR52 agonist supports therapeutic utility as novel treatment for positive symptoms and cognitive dysfunction in psychotic disorders including schizopherenia
By Cliona MacSweeney et al. | Dec 12, 2019
Cliona MacSweeney, Associate Director, Translational Sciences, attended American College of Neuropsychopharmacology (ACNP) 2019 in Florida, US on 8-11 December and presented on Modulation of dopaminergic and glutamatergic function by GPR52 agonist supports therapeutic utility as novel treatment for psychosis.READ MORE...