TIY-7

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上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

TIY-7 

TIY-7 是一种选择性和具有口服活性的 原肌球蛋白受体激酶 (TRK) 抑制剂。TIY-7 对 TRKA, TRKAG595R, TRKAG667C, TRKAF589L, TRKCG623R, TRKCG696A 酶均显示出抑制活性其 IC50 值分别为 2.9, 1.1, 0.7, 0.8, 0.8, 0.2 nM。TIY-7 在小鼠异种移植模型中显示出抗肿瘤效力。

TIY-7

TIY-7 Chemical Structure

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生物活性

TIY-7 is a selective and orally active tropomyosin receptor kinase (TRK) inhibitor. TIY-7 shows enzyme inhibitory activity with IC50s of 2.9, 1.1, 0.7, 0.8, 0.8, 0.2 nM for TRKA, TRKAG595R, TRKAG667C, TRKAF589L, TRKCG623R, TRKCG696A, respectively. TIY-7 shows anti-tumor potency in mouse xenograft model[1].

IC50 & Target[1]

TrkA

2.9 nM (IC50)

体外研究
(In Vitro)

TIY-7 (compound 12c) shows enzyme inhibitory activity with IC50s of 2.9, 1.1, 0.7, 0.8, 0.8, 0.2 nM for TRKA, TRKAG595R, TRKAG667C, TRKAF589L, TRKCG623R, TRKCG696A, respectively[1].
TIY-7 (1 µM) shows selectivity with inhibitory rate of 62%, 99%, 11% for ALK, ROS1, and JAK1 kinase[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究
(In Vivo)

TIY-7 (5 mg/kg for p.o.; 1 mg/kg for i.v.) shows good oral bioavailability (F) of 39.8%[1].
TIY-7 (30 mg/kg; P.o.; twice daily for 12-14 consecutive days) inhibits tumor progression in a dose-dependent manner in xenograft model[1].
Pharmacokinetic Parameters of TIY-7 in Male Sprague-Dawley rats[1].

Dose (mg/kg) Cmax (ng/mL) Tmax (h) T1/2 (h) CL (mL/min/kg) F % MRT0-t (h) AUCtot (ng/mL·h) AUCextra (%)
ip mice 9.103 2078 0.0833 0.8 154 86 0.7 982.3 1.3
iv mice 0.711 322.7 0.0833 1.1 133 0.9 88.8 15.2
iv dog 26.76 272 (µg/mL) 0.0833 3.8 0.69 3.8 654.7 (µg/mL·h) 0.9

Male Sprague-Dawley rats; 5 mg/kg for p.o.; 1 mg/kg for i.v.[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Male Sprague-Dawley rats[1]
Dosage: 5 mg/kg for p.o.; 1 mg/kg for i.v.
Administration: P.o. or i.v.
Result: Showed good PK properties with an oral bioavailability (F) of 39.8%.
Animal Model: 6-week-old BALB/cA nude mice (BaF3-TMP3-TRKA-WT and BaF3-ETV6-TRKC-G623R xenograft models)[1]
Dosage: 30 mg/kg (dissolved in 70% PEG400 and 30% water)
Administration: P.o.; twice daily; 12-14 consecutive days
Result: Dose-dependently inhibited tumor progression with the TGI of 95% and 86% in BaF3-TMP3-TRKA-WT and BaF3-ETV6-TRKC-G623R xenograft model.

分子量

446.40

Formula

C21H18F4N6O
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献

  • [1]. Mei LC,et al. Conformational adjustment overcomes multiple drug-resistance mutants of tropomyosin receptor kinase. Eur J Med Chem. 2022 Apr 25;237:114406.

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