How Best to Assess Molecular Shapeliness?
The recent open‑access Drug Discovery Today paper evaluates three common metrics for quantifying molecular three‑dimensionality: fraction of sp3‑hybridized carbons (FCsp3), plane of best fit (PBF), and principal moments of inertia (PMI) expressed as ΣNPR. An analysis of half a million commercial fragments shows that FCsp3 does not correlate with PMI, making it a poor proxy for shape, while PBF aligns with ΣNPR once normalized for molecular size. The authors also test extensions such as FHAsp3 and normalized spacial scores, which offer no improvement. They conclude that PBF and PMI both reliably capture shapeliness, but PMI provides finer discrimination between rod‑like and disc‑like geometries.
Review of 2025 Reviews
The Practical Fragments blog celebrated its thousandth post in 2025, highlighting a decade of fragment‑based drug discovery (FBDD) milestones. Key reviews covered fragment‑to‑lead successes, the rise of covalent fragments, AI‑driven cryptic pocket discovery, and extensive bibliometric analysis showing steady global...
GAS41 Revisited: A Chemical Probe
Researchers at the University of Michigan have refined a fragment‑based series into DLG‑41, a monomeric chemical probe targeting the YEATS domain of GAS41. The probe exhibits ~1 µM affinity by ITC and nanomolar potency in a NanoBRET cellular assay, confirming both...