PDBsum entry 6pme

Transferase

PDB id: 6pme

Contents

Protein chains

268 a.a.

Ligands

OOY ×3

SRT ×2

Metals

_ZN ×3

Waters ×1

References listed in PDB file

Key reference

• Title: Synthetic inhibitor leads of human tropomyosin receptor kinase a (htrka).
• Authors: G.Subramanian, R.Vairagoundar, S.J.Bowen, N.Roush, T.Zachary, C.Javens, T.Williams, A.Janssen, A.Gonzales.
• Ref.: RSC Med Chem, 2020, 11, 370-377. [DOI no: 10.1039/c9md00554d]
• PubMed id: 33479642

Abstract

In silico virtual screening followed by in vitro biochemical, biophysical, and cellular screening resulted in the identification of distinctly different hTrkA kinase domain inhibitor scaffolds. X-ray structural analysis of representative inhibitors bound to hTrkA kinase domain defined the binding mode and rationalized the mechanism of action. Preliminary assessment of the sub-type selectivity against the closest hTrkB isoform, and early ADME guided the progression of select inhibitor leads in the screening cascade. The possibility of the actives sustaining to known hTrkA resistance mutations assessed in silico offers initial guidance into the required multiparametric lead optimization to arrive at a clinical candidate.