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
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So far Al Dossetter has created 36 blog entries.
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
Structure-Based Design of Potent, Selective, and Orally Bioavailable VPS34 Kinase Inhibitors This month’s paper is an excellent piece of work from our friends at Genentech. It is noteworthy and commendable of the authors to publish this work, as the project did not produce a candidate drug. The authors describe the compounds and SAR to aid
Available Immediately - Direct SARkush We have added a lightweight GUI interface to MCPairs Online, that is immediately available to all users. This front end is similar to MyPairs and the input files are the same type. For comp.chem. the mcpcli route is still available, but this method provides is useful for those who are
From PhD to Drug Hunter By Dr Jess Stacey When I first arrived at MedChemica, I was given the task to create a new tool that makes small changes to a molecule's core, whilst ensuring suggestions are realistic and synthetically tractable. This scaffold hoping tool become known as CoreDesign®, see Figure 1. At the time
Boosting Protein−Ligand Binding Pose Prediction and Virtual Screening Based on Residue−Atom Distance Likelihood Potential and Graph Transformer J. Med. Chem. 2022, 65, 10691−10706 We have an interest in MedChemica in following developments in virtual screening. The paradigm of protein sequence identification, computer folding to yield a 3D structure, pocket identification, then virtual screening yielding small
Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306 This med chem paper is an excellent write up of a candidate drug discovery, starting with the screening hit. It is remarkable, as a small deck of 560 kinase inhibitors were screened at the start, and this only yielded a couple of hits. One of
Not Burning Enough Calories: An odd thing has happened, well not that odd really. I wrote recently about the joy of Green Commuting. Last month we moved office to the centre of Macclesfield, which is so much closer to where I live. So what is odd? It mush be easier to Green commute now –
Bicycle Race - By Queen (given a bit of an updated for summer 2022 by Al Dossetter) Bicycles, bicycles, bicycles We want to ride our bicycles, bicycles, bicycles We want to ride our bicycles We want to ride our bikes We want to ride our bicycles We want to ride it where we like You
There be Rings in them Drugs This month, we choose to highlight a paper published by researchers at UCB in which cheminformatics techniques were utilised to provide a detailed analysis of the ring systems present in drug and clinical trial compounds. Using a virtual fragmentation technique on drug and clinical trial compound libraries, the authors