Quantum Chemical Evaluation and QSAR Modeling of N-Nitrosamine Carcinogenicity N-Nitrosamines (compounds containing the R2N-N=O structural motif) are present in our food, the environment and some pharmaceutical impurities, with several N-nitrosamines known to be carcinogenic. This month’s paper of the month is a modelling study by Schieferdecker and Vock from Boehringer Ingelheim that aimed to quantitatively

Discovery of 6‐Fluoro-5-{4-[(5-fluoro-2-methyl-3-oxo-3,4- dihydroquinoxalin-6 yl)methyl]piperazin-1-yl}‐N‐methylpyridine-2- carboxamide (AZD9574): A CNS-Penetrant, PARP1-Selective Inhibitor J. Med. Chem., 2024, 67, 21717–21728   DNA damage, such as double-strand breaks (DSB), single strand nicks (SSB), gaps and more occur naturally within cell nuclei and can also be induced by environmental factors such as radiation. Key defences against these cytotoxic or oncogenic

A covalent chemical probe for Chikungunya nsP2 cysteine protease with anti-alphaviral activity and proteome-wide selectivity Sci. Rep., 2025, 15, 7264   Neglected tropical diseases (NTDs) are a diverse group of infections and ailments that are commonly encountered in low- and middle-income countries that receive few resources and research attention relative to “The Big Three”: Malaria, HIV/AIDS and tuberculosis.  NTDs are

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