The Chemical and Temporal Landscape of KDM1A (LSD1) Bioactivity Space: A Data-Driven Cheminformatic Analysis of Public ChEMBL Data on Potency, Scaffold Diversity and Physicochemical Properties
DOI:
https://doi.org/10.63282/3050-9262.IJAIDSML-V7I4P101Keywords:
KDM1A/LSD1, Chemical Space, Scaffold Diversity, ChEMBL, Cheminformatics, Data ScienceAbstract
Lysine-specific histone demethylase 1A (KDM1A, also known as LSD1) is a validated epigenetic anticancer target, yet the collective chemical space of its reported bioactive compounds is seldom mapped as a whole. This study presents a purely descriptive cheminformatic profile of that space from the public ChEMBL database. Of 3,946 compounds with a defined pChEMBL value for the human target CHEMBL6136, the 3,435 (87.1 percent) reporting IC50 as their only endpoint form the primary set. Structures are processed with RDKit and statistics with SciPy and pandas; no predictive modelling, docking, molecular dynamics, ADMET prediction or quantum-chemical calculation is performed. Measured potency spans pChEMBL 3.36 to 10.30 with a median of 6.75, comprising 2,546 high-potency, 523 moderate and 366 low-potency compounds. The set maps to 1,658 Bemis-Murcko scaffolds and 948 generic frameworks, 56 percent of which are singletons; 80 and 339 frameworks cover 50 and 80 percent of compounds (Shannon entropy 8.72 of 9.89 bits; Gini coefficient 0.60). Median potency differs significantly among the most frequent frameworks (Kruskal-Wallis test, p below 0.001). Records concentrate in 2011 to 2025 and peak in 2022 and annual median potency shows a modest but significant upward trend (Spearman correlation 0.66, p value 0.008). Median molecular weight is 419 Da, calculated logP 3.8 and topological polar surface area 72 square angstroms; 30 peptidic or macrocyclic outliers exceed 1,000 Da and 9.9 percent of compounds carry a PAINS alert. This transparent, reproducible map offers a model-free reference for scaffold selection and gap analysis in KDM1A drug discovery.
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