Product Data?SheetEntrectinibCat. No.:CAS No.:分?式:分?量:作?靶点:作?通路:储存?式:HY-126781108743-60-7C??H??F?N?O?560.64ROS; Trk Receptor; ALK; AutophagyProtein Tyrosine Kinase/RTK; Neuronal Signaling; AutophagyPowderIn solvent-20°C4°C-80°C-20°C3 years2 years6 months1 monthInhibitors?Agonists?Screening Libraries溶解性数据体外实验DMSO : ≥ 31 mg/mL (55.29 mM)* \Mass1 mg5 mg10 mgSolventConcentration制备储备液1 mM5 mM10 mM1.7837 mL0.3567 mL0.1784 mL8.9184 mL1.7837 mL0.8918 mL17.8368 mL3.5674 mL1.7837 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；?旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存?式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个?内使?，-20°C 储存时，请在 1 个?内使?。体内实验请根据您的实验动物和给药?式选择适当的溶解?案。以下溶解?案都请先按照 In Vitro ?式配制澄清的储备液，再依次添加助溶剂： 为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的?作液，建议您现?现配，当天使?； 以下溶剂前显?的百分?是指该溶剂在您配制终溶液中的体积占?；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的?式助溶1. 请依序添加每种溶剂：?10% DMSO ?? 40% PEG300 ?? 5% Tween-80 ?? 45% salineSolubility: ≥ 2.5 mg/mL (4.46 mM); Clear solution此?案可获得 ≥ 2.5 mg/mL (4.46 mM，饱和度未知) 的澄清溶液。 以 1 mL ?作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加? 50 μL Tween-80，混合均匀；然后继续加? 450 μL ?理盐?定容? 1 mL。2. 请依序添加每种溶剂：?10% DMSO ?? 90% corn oilSolubility: ≥ 2.5 mg/mL (4.46 mM); Clear solutionPage 1 of 2 www.MedChemExpress.cn
此?案可获得 ≥ 2.5 mg/mL (4.46 mM，饱和度未知) 的澄清溶液，此?案不适?于实验周期在半个?以上的实验。 以 1 mL ?作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL ??油中，混合均匀。
BIOLOGICAL ACTIVITY
?物活性
Entrectinib (NMS-E628) 是有效，有?服活性的且具有中枢神经活性的 Trk, ROS1 和 ALK 抑制剂，抑制 TrkA, TrkB, TrkC, ROS1 和 ALK 的IC50 值分别为 1, 3, 5, 12 和 7 nM。具有抗肿瘤活性。
IC?? & Target体外研究
IC50: 1 nM (TrkA), 1 nM (TrkB), 1 nM (TrkC), 1 nM (ROS1),1 nM (ALK)[1]
Entrectinib (NMS-E628) is found to be exquisitely active in inhibiting the proliferation of a limited number of cell lines: the TRKA-driven colorectal carcinoma cell line KM12 (IC50 of 17 nM), the ALK-dependent ALCL cell lines SU-DHL-1, Karpas-299, SUP-M2 and SR-786 (IC50 of 20, 31, 41, and 81 nM, respectively), the ALK-dependent NSCLC cell line NCI-H2228 (IC50 of 68 nM) and the FLT3-dependent AML cell line MV-4-11 (IC50 of 81 nM). Entrectinib potently blocks proliferation of Ba/F3-TEL-TRKB (IC50 of 2.9 nM), Ba/F3-TEL-TRKC (IC50 of 3.3 nM), and Ba/F3-TEL-ROS1 (IC50 of 5.3 nM) cells, with a high degree of selectivity versus parental Ba/F3 cells or those transformed by nontargeted kinases such as ABL and RET, which are inhibited with IC50s in the range of 2 to 3 μM[1]. Entrectinib significantly inhibits the growth of TrkB-expressing NB cells in vitro, and it significantly enhances the growth inhibition of Irino-TMZ when used in combination[2].
体内研究
Oral administration of entrectinib to tumor-bearing mice induces regression in relevant human xenograft tumors, including the TRKA-dependent colorectal carcinoma KM12, ROS1-driven tumors, and several ALK-dependent models of different tissue origins, including a model of brain-localized lung cancer metastasis[1]. Single agent therapy results in significant tumor growth inhibition in animals treated with entrectinib compared to control animals[2].
PROTOCOL
Cell Assay [2]
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].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal
Administration [2]
Mice: Entrectinib is reconstituted in 0.5% methylcellulose containing 1% Tween 80 at a final dosing volume of 10 mL/kg (e.g., 0.2 mL for a 20 gm mouse). Treatment with entrectinib, Irino and TMZ started about 15–17 days after tumor inoculation when the average tumor size is 0.2 cm3. Mice are sacrificed when tumor volume reached 3 cm3. Tumors are harvested and flash frozen on dry ice for analysis of protein expression[2].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
客户使?本产品发表的科研?献
????Science. 2017 Dec 1;358(6367). pii: eaan4368.????Mol Cancer Ther. 2017 Oct;16(10):2130-2143.????Oncol Rep. 2018 Aug;40(2):635-646.
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????Clin Chim Acta. 2018 Oct;485:298-304.
See more customer validations on www.MedChemExpress.cnREFERENCES
[1].?Ardini E, et al. Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications. Mol Cancer Ther. 2016 Apr;15(4):628-39.
[2].?Iyer R, et al. Entrectinib is a potent inhibitor of Trk-driven neuroblastomas in a xenograft mouse model. Cancer Lett. 2016 Mar 28;372(2):179-86.
McePdfHeightCaution: Product has not been fully validated for medical applications. For research use only.
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