Discovery of the Clinical Candidate S‑892216: A Second-Generation of SARS-CoV‑2 3CL Protease Inhibitor for Treating COVID-19 Coronavirus infections are widespread, with symptoms of varying severity depending on the virus and the individual circumstances of the patient. In 2022, Shionogi disclosed the structure of ensitrelvir, an orally bioavailable non-covalent, non-peptidomimetic Coronavirus Main Protease (CoV MPro) inhibitor

AI in drug design: evolution or revolution? Darren sets out to explore the impact of artificial intelligence (AI) on the pharmaceutical industry, particularly in the drug discovery sector. He begins by setting out the different AI methods, such as machine learning (ML; models that learn from previous data), deep learning (ML models that mimic human

One Chiral Fingerprint To Find Them All Markus Orsi & Jean-Louis Reymond. J. Cheminform., 2024, 16:53 doi: 10.1186/s13321-024-00849-6 In Chemoinformatics there are a few problems that always rear their ugly heads and stereochemistry is one of them, even though many computational tools use fingerprints which generally do not consider this. Orsi and Reymond have created

Identification of Novel, Selective Ataxia-Telangiectasia Mutated Kinase Inhibitors with the Ability to Penetrate the Blood−Brain Barrier: The Discovery of AZD1390 Achieving CNS penetration, when desired, is a hugely important and sometimes very difficult hurdle to overcome. To do this, the Blood-Brain Barrier (BBB): with its unique lining of endothelial cells and its cocktail of efflux

The First ATP Competitive Type-III c-MET Inhibitor? In this paper, the target was c-MET, which is a receptor tyrosine kinase implicated in the development of tumour cells. Hyperactivation of c-MET is associated with poor prognoses in cancer patients, including tumour survival and metastasis. Existing inhibitors of c-MET are clustered into types, depending on their site

Where Old Meets New: Advancements in AlphaFold with Some Help From Boltzmann   With the news saturated by the opportunities presented by AI, it’s easy to assume that AI alone holds all of the answers to our problems in computer-aided drug discovery. Indeed, the release of the ground-breaking protein structure prediction tool AlphaFold2, was an

Fast calculation of hydrogen-bond strengths and free energy of hydration of small molecules For this month’s computational chemistry paper of the month, we have chosen to highlight Jazzy, a python package to calculate the strengths of hydrogen-bonds. As we all know the importance of hydrogen bond donors and acceptors in the drug discovery process. Within

Discovery of the Potent and Selective MC4R Antagonist PF-07258669 for the Potential Treatment of Appetite Loss In this Drug Annotation, the discovery of an antagonist of the melanocortin-4 receptor (MC4R) and clinical candidate: PF-07258669 is described. MC4R signalling is responsible for the regulation of food intake via the suppression of appetite. Inhibition of this target

Med Chem Paper of the Month – Jan/Feb 2023 This paper is a fine exhibition of multi-parameter optimisation that resulted in the candidate drug: MK-8189, currently undergoing phase II clinical trials for the treatment of schizophrenia. Discovery of MK-8189, a Highly Potent and Selective PDE10A Inhibitor for the Treatment of Schizophrenia   Schizophrenia is a debilitating