Practical Computational Exploration of Chemical Reaction Space: Assessing the Chemical Stability of Active Pharmaceutical Ingredients Under Acidic Conditions. (PubMed, Angew Chem Int Ed Engl) - Sep 15, 2026 - "Applied to the acid-catalysed degradation of BMS-644950, the workflow constructs a network of 1720 species and 2471 elementary steps, reduced to 8 degradation products...The calculations reveal that several thermodynamically favourable products remain unobserved because activation barriers of 36-40 kcal render them kinetically inaccessible on the experimental timescale, a distinction reaction-rule-based methods cannot make. The exploration finishes within 3 days on a compute cluster, demonstrating that automated, physics-based degradation modelling is tractable for drug-like molecules at industrially relevant scales."
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Andreas H Göller; Jan H Jensen; Julius Seumer; Maria Harris Rasmussen; Mikko Muuronen; Oriana Brea
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