CH7057288是一种新型的、具有口服活性的TRK抑制剂。
Cas No.:2095616-82-1
Sample solution is provided at 25 µL, 10mM.
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CH7057288 is a novel, orally active TRK inhibitor. CH7057288 inhibits the activity of TRKA (IC50=1.1nM), TRKB (IC50=7.8nM), and TRKC (IC50=5.1nM) to block tumor cell proliferation, while also reducing tumor growth by inhibiting the MAPK and E2F signaling pathways. CH7057288 is suitable for research related to TRK fusion-positive cancers[1-2].
In vitro, treatment of TRK fusion-positive cell lines (such as NIH3T3 MPRIP-NTRK1 and CUTO-3) with CH7057288 (8.4–67nM) for 4–7 days. CH7057288 significantly inhibited cell proliferation[1]. CH7057288 (0.1µM-1mM) also inhibited the proliferation of TRK fusion-positive cell lines (including CUTO-3, KM12-Luc, and MO-91) after 4 or 7 days of treatment, by inhibiting TRK autophosphorylation to block MAPK and E2F signaling pathways[2].
In vivo, oral administration of CH7057288 (0.6-10mg/kg) once daily for 4 weeks to NCG mouse models bearing implanted TRK fusion-positive tumors (such as KM12-Luc). CH7057288 significantly inhibited tumor growth[2].
References:
[1] Ito T, Kinoshita K, Tomizawa M, et al. Discovery of CH7057288 as an Orally Bioavailable, Selective, and Potent pan-TRK Inhibitor. J Med Chem. 2022 Sep 22;65(18):12427-12444.
[2] Tanaka H, Sase H, Tsukaguchi T, et al. Selective TRK Inhibitor CH7057288 against TRK Fusion-Driven Cancer. Mol Cancer Ther. 2018 Dec;17(12):2519-2529.
CH7057288是一种新型的、具有口服活性的TRK抑制剂。CH7057288可抑制TRKA（IC50=1.1nM）、TRKB（IC50=7.8nM）和TRKC（IC50=5.1nM）的活性来阻断肿瘤细胞增殖，同时通过抑制MAPK和E2F信号通路以减少肿瘤生长，CH7057288可用于TRK融合阳性癌症的相关研究[1-2]。
在体外，CH7057288（8.4–67nM）处理TRK融合阳性细胞系（如NIH3T3 MPRIP-NTRK1、CUTO-3）4–7天。CH7057288显著抑制细胞增殖[1]。CH7057288（0.1μM-1mM）处理TRK融合阳性细胞系（CUTO-3、KM12-Luc、MO-91等）4天或7天，能够抑制细胞增殖，同时通过抑制TRK自身磷酸化来阻断其下游的MAPK和E2F信号通路[2]。
在体内，CH7057288（0.6-10mg/kg）每天一次口服给药，用于处理接种了TRK融合阳性肿瘤（如KM12-Luc）的NCG小鼠模型4周。CH7057288能够显著抑制肿瘤的生长[2]。
| Cell experiment [1]: | |
Cell lines | TRK fusion-positive cancer cell lines (e.g., NIH3T3 MPRIP-NTRK1, CUTO-3, KM12-Luc) |
Preparation Method | TRK fusion-positive cancer cells were treated with CH7057288 (8.4–67nM) for 4 to 7 days. |
Reaction Conditions | 8.4–67nM; 4-7 days. |
Applications | CH7057288 potently inhibited the proliferation of TRK fusion-positive cell lines by inhibiting TRK auto-phosphorylation and blocking downstream MAPK and E2F signaling pathways. |
| Animal experiment [2]: | |
Animal models | NCG mice bearing subcutaneous NIH3T3 MPRIP-NTRK1 tumors (or CUTO-3 NSCLC xenografts) |
Preparation Method | Mice were orally administered CH7057288 (0.6-10mg/kg) once daily for 4 weeks. |
Dosage form | 0.6-10mg/kg; p.o.; Daily for 4 weeks. |
Applications | CH7057288 induced potent tumor growth inhibition in the NIH3T3 MPRIP-NTRK1 model and CUTO-3 model. Importantly, no significant body weight loss was observed. |
References: | |
| Cas No. | 2095616-82-1 | SDF | |
| Canonical SMILES | O=C1C2=C(OC3=CC(C#CC4=CC(C(NC(C)(C)C)=O)=CC(C)=N4)=CC=C23)C(C)(C)C5=CC(NS(C)(=O)=O)=CC=C15 | ||
| 分子式 | C32H31N3O5S | 分子量 | 569.67 |
| 溶解度 | DMSO : ≥ 34 mg/mL (59.68 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7554 mL | 8.777 mL | 17.554 mL |
| 5 mM | 351.1 μL | 1.7554 mL | 3.5108 mL |
| 10 mM | 175.5 μL | 877.7 μL | 1.7554 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet