Real-World Applications and Experiences of AI/ML Deployment for Drug Discovery After listening to Rob Young’s talk at the Chemist in Industry about “Fads and Fashion in Drug Discovery” where he spoke about whether artificial intelligence (AI) is all that it is made out to be within the drug discovery process, I started to investigate further.

Faster Sampling in Molecular Dynamics Simulations with TIP3P-F Water A significant challenge for using MD to sample configurations and determine equilibrium properties of biomolecular systems, is the computation required to sufficiently sample the timescales necessary to observe the relevant thermodynamic minima. In order to sample biomolecular events within reasonable timeframes, computational chemists often employ enhanced

Discovery of Rezatapopt (PC14586), a First-in-Class, Small-Molecule Reactivator of p53 Y220C Mutant in Development ACS Med. Chem. Lett., 2025, 16, 1, 34–39   Precision medicine (used interchangeably with “personalised medicine”) is a broad term that refers to the grouping of patient populations into those that are likely to respond to a particular treatment and those

  Figure 1: The Structure of zoliflodacin   Introduction Zoliflodacin (Figure 1, above) is an orally administered DNA gyrase (topoisomerase) inhibitor, under study for the treatment of Gonorrhoea. The Global Antibiotics Research and Development Partnership (GARDP) recently announced that the primary endpoint for its phase 3 clinical trial (noninferiority to ceftriaxone/azithromycin) was met.1,2 In isolation,

Estimating the synthetic accessibility of molecules with building block and reaction-aware SAScore JCIM. 2024. ISSN: 1758-2946 The one question most chemists ask when viewing molecules generated using computational tools, machine-learning methods or AI models is but how easy is it to make? MedChemica users will know that we use Peter Ertl’s SAScore1 within CoreDesign to

Development of Brain Penetrant Pyridazine Pantothenate Kinase Activators Med. Chem.2024, 67, 14432-14442   Coenzyme A (CoA) is a thiol cofactor that carries carboxylic acid substrates to where they are needed in important metabolic pathways, such as the Citric Acid Cycle. CoA is biosynthesised from pantothenic acid (Vitamin B5). The first and rate-limiting step of this

N‐Substituted Pyrrole-Based Heterocycles as Broad-Spectrum Filoviral Entry Inhibitors   J. Med. Chem.2024, 67, 13737-13764   Emerging pathogenic viruses of pandemic potential remain a global public health concern. In recent decades, outbreaks of 2 significant members of the Filovirus family (Filoviridae): Ebola virus (EBOV) and Marburg virus (MARV) have occurred, resulting in thousands of deaths in

Prediction of Inhibitory Activity against the MATE1 Transporter via Combined Fingerprint- and Physics-Based Machine Learning Models The multidrug and toxin extrusion transporter (MATE1) is located in the renal epithelial cells and mediates efflux of organic cations, like metformin. It is understood that clinical inhibitors of organic cation transporters may also inhibit MATE1, which causes concern

Discovery of JAB-3312, a Potent SHP2 Allosteric Inhibitor for Cancer Treatment Wei Long et al J. Med. Chem. 2024, 67, 13534−13549     This paper in the August addition has promoted a little bit of a SHP2 inhibitor profile – so more a suite of papers than a paper of the month... There are two

Simulation-driven design of stabilized SARS-CoV-2 spike S2 immunogens During the European Federation for Medicinal Chemistry – International Symposium on Medicinal Chemistry (EFMC-ISMC) 2024, I attended an inspiring lecture by Dr Rommie Amaro from University of California in which she enthusiastically demonstrated the usefulness of molecular dynamics simulations to impact drug and vaccine design by increasing