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Entrectinib

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Chemical Structure| 1108743-60-7 同义名 : NMS-E628;RXDX-101
CAS号 : 1108743-60-7
货号 : A119591
分子式 : C31H34F2N6O2
纯度 : 99%+
分子量 : 560.638
MDL号 : MFCD28129099
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 30 mg/mL(53.51 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 10 mg/mL clear

PO 0.5% CMC-Na 30 mg/mL suspension

生物活性
靶点

  • ALK
描述 RTKs (receptor tyrosine kinases) and the RTK signaling pathways play an important role in cellular processes. The oncogenic activation of specific RTKs is the molecular target in advanced non-small cell lung cancer. Entrectinib is a multiple target inhibitor of TrkA, TrkB, TrkC, ROS1 and ALK inhibitor with IC50 values of 1.7, 0.1, 0.1, 0.2 and 1.6nM, respectively. Entrectinib exhibited in vitro anti-proliferative activity with IC50 value of 17nM in KM-12, a human colorectal cancer cell line driven by constitutively active TrkA fusion TPM3-NTRK1, accompanied by inhibition on p-TrkA and the inactivation of its downstream effectors, p-PLCγ1, p-AKT and p-ERK at dose of 10-250nM in 2h, as well as cell cycle arrest and apoptosis. Different manners in oral treatment with Entrectinib, including RXDX-101 at dose 15, 30 and 60mg/kg, BID for 10 days, 15mg/kg BID with 4 days on/ 3 days off for 3 cycles, and 15mg/kg continuously for 3 weeks, resulted in tumor regression and durable stasis in mice bearing KM-12 xenografts, accompanied by sustained intratumoral inhibition of p-TrkA and p-PLCγ1. These suggest that Entrectinib may be a promising therapeutic agent for patients with oncogenic Trk alterations[1].
作用机制 Entrectinib is an ATP-competitive inhibitor of the tyrosine kinases TrkA, TrkB, TrkC, ROS1, and ALK.[1]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.78mL

0.36mL

0.18mL

8.92mL

1.78mL

0.89mL

17.84mL

3.57mL

1.78mL
参考文献

[1]D. Anderson, M. Ciomei, et al. Inhibition of Trk-driven tumors by the pan-Trk inhibitor RXDX-101. ejcancer. Volume 50, Supplement 6, Page 101.

[2]Iyer R, Wehrmann L, et al. Entrectinib is a potent inhibitor of Trk-driven neuroblastomas in a xenograft mouse model. Cancer Lett. 2016;372(2):179-86.

[3]Ardini E, Menichincheri M, et al. Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications. Mol Cancer Ther. 2016;15(4):628-39.

[4]Entrectinib for the Treatment of Pediatric Cancers Harboring an Activating Alteration of NTRK1/2/3, ROS1, or ALK