Machine Learning Strategies for Reaction Development: Toward the Low-Data Limit This useful perspective article discusses many recent attempts at applying machine learning strategies (particularly transfer and active learning) to reaction improvement and discovery. The authors present many of the examples where researchers have sought to apply these methods and achieve a balanced perspective on the

Discovery of an Oral, Beyond-Rule-of-Five Mcl‐1 Protein−Protein Interaction Modulator with the Potential of Treating Hematological Malignancies. In this paper, researchers from Janssen Pharmaceuticals were searching for a bespoke inhibitor of myeloid cell leukemia 1 (Mcl-1), which is among a family of proteins that regulate apoptosis, and is over-expressed in a number of hematological cancers and

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

MCPairs v1.9 release is automatically available to all users: MCPairs version 1.9 went live last weekend. All Online users are upgraded to the new platform, and all new tools are available to everyone. On logging on you will notice the change in the layout of the dashboard as CoreDesign® has been added. This joins RuleDesign®

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

    A Review of Computational Approaches Targeting SARS-CoV-2 Main Protease to the Discovery of New Potential Antiviral Compounds   Current Topics in Medicinal Chemistry, 2023, 23, 3-16   For this month’s computational chemistry paper of the month, we have chosen to highlight a recent review of the computational approaches used to identify inhibitors of

Recent bRo5 publications Figure 1: Picture summarising the limitations of obeying the Ro5 and the versatility obtained by going beyond (www.sciencedirect.com/science/article/abs/pii/S1367593117300480?via%3Dihub). Cast our minds back... It’s been more than 25 years since a Pfizer chemist: Christopher Lipinski, published1 his influential analysis of the calculated physical properties of a set of candidate drugs, leading to the well-known

Exposing the Limitations of Molecular Machine Learning with Activity Cliffs J. Chem. Inf. Model. 2022, 62, 5938−5951 The title of this paper pulled in my attention immediately. The authors performed a comprehensive study of the ability of ML and DL to predict the larger drops in potency that can occur with small structural changes. Activity

Design and Structural Optimization of Orally Bioavailable SOS1 Inhibitors for the Treatment of KRAS-Driven Carcinoma J. Med. Chem. 2022, 65, 15856−15877 This is a biased pick – we wrote a review on SOS1 inhibitors a year or so ago – so there you go [https://doi.org/10.1080/13543776.2021.1952984]. At the start of my career the pharma company I