Efficient Crystallization of Apo Sirt2 for Small-Molecule Soaking and Structural Analysis of Ligand Interactions   J. Med. Chem. 2024, 67, 15, 12461–12462 Sirtuin proteins (Silent Information Regulators, Sirt1-7) are NAD+-dependent enzymes that have a range of important functions as metabolic regulators, depending on their subcellular localisation. This family of enzymes is relevant to the discovery

Exploration of structure-activity relationships for the SARS-CoV-2 macrodomain from shape-based fragment linking and active learning One of the known challenges in drug discovery is finding good initial hit compounds in the vast expanse of druglike chemical space. Traditional high throughput screening (HTS) libraries only cover a small area of chemical space and are costly to

Summary of the ACSMEDI-EFMC Medicinal Chemistry Frontiers in May 2025 In May, we had a great time exhibiting at the ACSMEDI-EFMC Medicinal Chemistry Frontiers in Chicago. We enjoyed catching up with clients to discuss how our medicinal chemistry consultants can lead/advise on projects and how our MCPairs software can help chemists choose which compounds to

Cheminformatic Analysis of Core-Atom Transformations in Pharmaceutically Relevant Heteroaromatics J. Med. Chem., 2025, 68, 6, 6027–6040 The art of medicinal chemistry involves discovering molecules that represent a compromise between target potency and in-vivo pharmacokinetic properties. Only after a successful balancing act between these two (sometimes conflicting) factors has been achieved, is it possible to propose a

Visualising lead optimisation series using reduced graphs Journal of Cheminformatics This month’s paper of the month has been recently published by our Senior Computational Chemist, Jess Stacey, for her PhD work that she undertook at the University of Sheffield. They were using Reduced Graphs (RG) to visualise lead optimisation series, indicating areas that have been

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