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Selitrectinib

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Chemical Structure| 2097002-61-2 同义名 : LOXO-195;BAY 2731954
CAS号 : 2097002-61-2
货号 : A285925
分子式 : C20H21FN6O
纯度 : 99%+
分子量 : 380.419
MDL号 : MFCD31620755
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 60 mg/mL(157.72 mM)，配合低频超声助溶，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：
生物活性
描述 LOXO-195 is a new-generation and selective TRK inhibitor with IC50 values of 0.6nM, 2nM, 9.8nM, <2.5nM, 2.3nM and <2.5nM for TrkAWT, TrkAG595R, TrkAG667C, TrkCWT, TrkCG623R and TrkCG696A, respectively. Consistent with this, LOXO-195 displayed potent inhibitory effect on p-TRK in NIH-3T3 cells expressing TRK kinase acquired resistance mutations (IC50 1.6-64nM), with decrease p-ERK level (IC50 2-45nM) observed. Oral administration of LOXO-195 at dose of 30mg/kg, 100mg/kg and 300mg/kg, BID, led a dose-dependent tumor growth inhibition of mice xenograft these NIH-3T3 cells expressing different TRK resistance mutations. Distinguished from the other Trk inhibitor like larotrectinib, LOXO-195 abrogated resistance in TRK fusion–positive cancers that acquired kinase domain mutations, a shared liability with all existing TRK TKIs[1].
作用机制 The specific structure of LOXO-195 with ability to accommodate the bulky, positively charged arginine side chain in the solvent front without any steric clashes distinguishes it from the other Trk inhibitor like larotrectinib.[1]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.63mL

0.53mL

0.26mL

13.14mL

2.63mL

1.31mL

26.29mL

5.26mL

2.63mL
参考文献

[1]Drilon A, Nagasubramanian R, et al. A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion-Positive Solid Tumors. Cancer Discov. 2017 Sep;7(9):963-972.

[2]Sparidans RW, Li W, et al. Bioanalytical assay for the novel TRK inhibitor selitrectinib in mouse plasma and tissue homogenates using liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Aug 1;1122-1123:78-82.

[3]Drilon A, Nagasubramanian R, et al. A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion-Positive Solid Tumors. Cancer Discov. 2017 Sep;7(9):963-972.