Fig 1: JND4135 displays TRK kinase inhibitory activities against both wild-type (WT) and resistant mutation. (A) structure of JND4135; and representative graphs of kinase inhibitory activities of JND4135 against TRKA (B), TRKB (C), TRKC (D) and TRKA-G667C (E). All kinase inhibitory assays included at least two independent experiments.
Fig 2: JND4135 suppresses TRK signaling pathway in TRK fusion-driven BaF3 cell lines. (A) JND4135 inhibited the TRKA signaling pathways in BaF3-CD74-TRKA, BaF3-CD74-TRKA-G595R and BaF3-CD74-TRKA-G667C cells. (B) JND4135 inhibited the TRKB signaling pathways in BaF3-ETV6-TRKB, BaF3-ETV6-TRKB-G639R and BaF3-ETV6-TRKB-G709C cells. (C) JND4135 inhibited the TRKC signaling pathways in BaF3-ETV6-TRKC, BaF3-ETV6-TRKC-G623R and BaF3-ETV6-TRKC-G696C cells. Cells were pretreated with 0–200 nmol/L of JND4135 for 6 h, then harvested and lysed. Cell lysates were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and analyzed by Western blot for p-TRK, p-PLCγ1 and p-Erk. GAPDH was used as a loading control.
Supplier Page from Abcam for Anti-TrkA (phospho Y496) + TrkB (phospho Y516) + TrkC (phospho Y516) antibody [EPR19140]