KinaseMD 2.0: an updated database of kinase mutations and drug response.

Abstract

Kinase mutations can alter activity, inhibitor response and downstream phosphorylation signaling, particularly within four resistance-associated substructures: gatekeeper, G-loop, αC-helix, and A-loop. KinaseMD 2.0 (http://modinfor.com/KinaseMD/) updates the kinase-centered database in three areas. Integrating source-curated annotations with Dr. Kinase predictions expanded substructure annotations from 1162 to 13 522 and kinase coverage from 388 to 547. Updated pharmacogenomic and signaling layers contain 422 244 drug-response measurements, 1614 candidate drug-resistance evidence records, and 359 600 predicted phosphorylation-network rewiring events. The new Kinase Perturbation Evidence Mapping (KPEM) workflow combines LLM-based literature extraction from an initial collection of over 480 000 publications with standardized processing of 30 public drug-treatment phosphoproteomic datasets. It provides 23 757 kinase-level records of literature-reported evidence and 53 029 phosphoproteomic records across 5124 drug/agent categories and 1598 disease contexts, distinguishing reported phosphorylation evidence from inferred kinase-associated signaling responses. By linking resistance-associated substructures, cancer mutations, drug response, and phosphorylation signaling, KinaseMD 2.0 supports studies of drug-resistance mechanisms and kinase-inhibitor design and development.

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