CH5183284 (Debio-1347)
(Synonyms: Debio 1347; CH5183284) 目录号 : GC10759
An inhibitor of FGFR1, 2, and 3
Cas No.:1265229-25-1
Sample solution is provided at 25 µL, 10mM.
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CH5183284 (Debio-1347) is a selective and novel inhibitor of FGFR with IC50 value of 9.3, 7.6, 22 and 290 nM for FGFR1, FGFR2, FGFR3 and FGFR4, respectively [1].
Fibroblast growth factor receptors (FGFRs) are tyrosine kinases and receptors for fibroblast growth factors and consist of FGFR1, FGFR2, FGFR3 and FGFR4. In cancer, FGFR is activated by point mutations, gene amplification or chromosomal translocations/rearrangements and is involved in angiogenesis, cell growth, cell migration, invasion and metastasis [1].
CH5183284 (Debio-1347) is a selective and novel FGFR inhibitor. In a competitive binding assay, CH5183284 (Debio-1347) binding with FGFR1, FGFR2, FGFR3, FGFR4 and KDR with Kd values of 20, 20, 25, 740 and 960 nM, respectively. In DMS114, SNU-16 and KMS11 cell lines, CH5183284 (Debio-1347) (100-300 nM) inhibited autophosphorylation of FGFR1, FGFR2 and FGFR3. In cancer cell lines with the FGFR genetic alterations, CH5183284 (Debio-1347) showed antiproliferative activity [1].
In xenograft mouse models, CH5183284 (Debio-1347) inhibited tumor growth against xenografts with FGFR genetic alterations such as KG1 (leukemia, FGFR1OP-FGFR1 fusion), MFE-280 (endometrial cancer, FGFR2 S252W mutation), SNU-16 (gastric cancer, FGFR2 amplification), RT112/84 (bladder cancer, FGFR3-TACC3 fusion) and UM-UC-14 (bladder cancer, FGFR3 S249C mutation) by 134%, 100%, 147%, 125% and 116%, respectively [1].
Reference:
[1]. Nakanishi Y, Akiyama N, Tsukaguchi T, et al. The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitor. Mol Cancer Ther, 2014, 13(11): 2547-2558.
| Kinase experiment [1]: | |
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Protein kinase assay |
The inhibitory activity of CH5183284/Debio 1347 against FGFR1 was evaluated using a radiometric filter assay by measuring the incorporation of 33Pi with a microplate scintillation counter. The phosphorylation activities of LCK, EGFR, KIT, MET, SRC, BRK, FGFR2, Flt3, LTK, INSR, YES, ABL, EPHA2, ZAP70, Fyn, IGF1R, KDR and PDGFR on substrate peptides were determined by homogeneous time-resolved fluorescence assay with LANCE Eu-W1024 labeled anti-phosphotyrosine PT66 antibody according to standard methods. Time-resolved fluorescence was measured with an EnVision HTS microplate reader. The activities of Aurora A, Akt1/PKBα, PKA, Cdk1/cyclin B, Cdk2/cyclin A, PKCα, PKCβ1 and PKCβ2 on substrate peptides were determined by IMAP FP Screening Express Progressive Binding System. Fluorescence polarization was measured with an EnVision HTS microplate reader. |
| Cell experiment [1]: | |
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Cell lines |
327 human tumor cell lines |
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Preparation method |
The solubility of this compound in DMSO is > 17.8 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
|
Reacting condition |
0.076 ~ 10,000 nM; 4 days |
|
Applications |
In DMS114 (FGFR1 amplification), SNU-16 (FGFR2 amplification) and KMS11 [t(4;14) translocation and FGFR3 Y373C mutation] cells, CH5183284 inhibited autophosphorylation of FGFR1, FGFR2 and FGFR3 at the dose range of 100 ~ 300 nM. Thus, CH5183284 selectively inhibited proliferation of cancer cell lines with genetic alterations in FGFR. In addition, CH5183284 also inhibited FGFR2-harboring cancer cells with V564F mutation which are resistant to other FGFR inhibitors. |
| Animal experiment [1]: | |
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Animal models |
Mice bearing KG1, MFE280, SNU-16, RT112/84 or UM-UC-14 xenografts |
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Dosage form |
100 mg/kg/day; p.o. |
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Applications |
CH5183284 exhibited selective and significant antitumor activities against various xenografts with FGFR genetic alterations such as KG1 (leukemia, FGFR1OP-FGFR1 fusion), MFE-280 (endometrial cancer, FGFR2 S252W mutation), SNU-16 (gastric cancer, FGFR2 amplification), RT112/84 (bladder cancer, FGFR3-TACC3 fusion) and UM-UC-14 (bladder cancer, FGFR3 S249C mutation). |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Nakanishi Y, Akiyama N, Tsukaguchi T, et al. The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitor. Mol Cancer Ther, 2014, 13(11): 2547-2558. | |
| Cas No. | 1265229-25-1 | SDF | |
| 别名 | Debio 1347; CH5183284 | ||
| Canonical SMILES | CC1=NC(C=C2)=C(N1)C=C2N3N=CC(C(C(N4)=CC5=C4C=CC=C5)=O)=C3N | ||
| 分子式 | C20H16N6O | 分子量 | 356.38 |
| 溶解度 | ≥ 35.6mg/mL in DMSO | 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 | 2.806 mL | 14.03 mL | 28.0599 mL |
| 5 mM | 0.5612 mL | 2.806 mL | 5.612 mL |
| 10 mM | 0.2806 mL | 1.403 mL | 2.806 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
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet