Entrectinib 是一种可口服的Trk、ROS1和ALK抑制剂，具有抗肿瘤和中枢神经活性，抑制 TrkA、TrkB、TrkC、ROS1 和 ALK 的IC50值分别为 1、3、5、12 和 7 nM。

Entrectinib is an inhibitor of TrkA (IC50: 1.7 nM), TrkB (IC50: 0.1 nM), and TrkC (IC50: 0.1 nM), as well as anaplastic lymphoma kinase (ALK; IC50: 1.6 nM) and C-ros oncogene 1 (ROS1; IC50: 0.2 nM). Entrectinib blocks proliferation of ALK-dependent cell lines, including those with C1156Y or L1196M resistance mutations, and inhibits ALK‐dependent signaling. It has been shown to inhibit the growth of a non-small cell lung Y cell line bearing an EML4-ALK rearrangement. In mice bearing various ROS1, Trk, or ALK-driven xenografts, Entrectinib has been shown to induce tumor regression.

Entrectinib effectively inhibits ALK‐dependent signaling and specificity blocks proliferation of ALK-dependent cell lines. Entrectinib also significantly inhibits cell growth of the NCI‐H2228 cell line bearing the EML4-ALK rearrangement.

In mice bearing Karpas-299 and SR-786 xenografts, Entrectinib (p.o.) induces complete tumor regression. In NPM-ALK transgenic mice, Entrectinib induces complete regression of tumor masses observed in the thymus and in lymph nodes. [2] In the NB xenograft model, Entrectinib cotreatment enhanced the efficacy of conventional chemotherapy. [3]

NLF, NLF-TrkB, SY5Y or SY5Y-TrkB cells are plated in 96 well plates, and they are exposed to drug at different concentrations (1, 5, 10, 20, 30, 50 and 100 nM of entrectinib, 1.5 μM Irino and 50 μM TMZ, respectively) for one hr followed by addition of 100 ng/mL of BDNF. Plates are harvested at 24, 48, and 72 hr following addition of drug. The plates are processed and cell viability is analyzed using a standard SRB assay protocol[2].

1108743-60-7

C31H34F2N6O2

560.65

RXDX-101;NMS-E628;恩曲替尼

Ethanol:67 mg/mL(119.5 mM)
DMSO:100 mg/mL (178.36 mM)
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years