Year: 2026
Type: preprint
Abstract: Early hit discovery normally begins with a physical or virtual collection of small molecules. Public resources such as PubChem, ChEMBL and ZINC have broadened access to chemical space, but using them effectively still requires retrieval, standardization, filtering, deduplication, three-dimensional preparation and provenance management; many laboratories also lack an in-house screening collection. We present DrugForge-ADMET v0.3.0, an open-source RDKit workflow intended to provide a compact, auditable starting set when a prepared library is unavailable. The software decomposes 30 inspectable, sp3-enriched seed templates into BRICS fragments, recombines them, sanitizes the products, and applies deterministic physicochemical rules, structural-alert catalogues and explicitly labelled descriptor-based risk proxies. Seed/reference similarity is assessed with radius-2, 2048-bit Morgan fingerprints and Tanimoto similarity; score-first diversity selection limits redundancy. Selected structures are exported as CSV and as SDF records with ETKDGv3 conformers followed, where parameterized, by MMFF or UFF optimization. In three fixed-seed technical validation runs, each capped at 10,000 enumerated products, 61, 157 and 194 candidates were selected. Across 412 outputs, 411 canonical SMILES were unique, all 412 SDF records were readable and all contained three-dimensional conformers. The pooled median values were molecular weight 355.50, cLogP 1.55, TPSA 79.25 Å2, fraction sp3 0.706, three rotatable bonds, one aromatic ring and QED 0.845. These results establish software execution and property-window compliance, not bioactivity, synthesizability, patent novelty or experimentally validated ADMET performance. DrugForge-ADMET is therefore positioned as a transparent candidate-generation and triage layer before target-specific modelling, retrosynthesis and experimental testing.
Source: ChemRxiv
Author: Erman Salih İSTİFLİ
Institution: Cukurova University
Language: English
Subfield: Drug Discovery
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7215067505