D5261

D5261 is a potent, type III allosteric tropomyosin-related kinase A (TrkA) inhibitor[1].

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Trk Receptor

TrkA

D5261 (0-10 µM, 72 h) displays favorable anti-proliferative activity in Ba/F3-MPRIP-TrkA cells (IC50 = 3.32 µM) and Ba/F3 CD74-TrkA cells (IC50 = 2.91 µM) [1]. D5261 exhibits cellular selectivity over TrkB/C to some extent (Ba/F3 IC50 > 10 µM, Ba/F3-QKI-TrkB IC50 = 6.17 µM and Ba/F3-EML4-TrkC IC50 > 10 µM)[1]. D5261 (0-50 µM) inhibits the TrkA autophosphorylation and downstream signaling in a concentration-dependent manner[1]. D5261 shows inhibitory activity against Ba/F3 cells harboring TrkA mutants (G667C, G667S, G667A, G595R and V573 M)[1]. Cell Viability Assay[1] Cell Line: Ba/F3-MPRIP-TrkA, Ba/F3 CD74-TrkA cells Concentration: 0-10 µM Incubation Time: 72 h Result: Displayed favorable anti-proliferative activity with an IC50 of 3.32 and 2.91 µM against Ba/F3-MPRIP-TrkA and Ba/F3 CD74-TrkA cells, respectively. Western Blot Analysis[1] Cell Line: Ba/F3 CD74-TrkA cells Concentration: 0.08, 0.4, 2, 10, and 50 µM Incubation Time: Result: Inhibited the TrkA autophosphorylation and phosphorylation of downstream PLCγ1, AKT and ERK in a concentration-dependent manner.

[1]. Jing Guo, et al. Discovery of novel TrkA allosteric inhibitors: Structure-based virtual screening, biological evaluation and preliminary SAR studies. Eur J Med Chem. 2022 Jan 15;228:114022.