BGJ398 (Infigratinib)
(Synonyms: FGFR抑制剂(NVP-BGJ398),BGJ398,BGJ-398,Infigratinib) 目录号 : GC10055
BGJ398 (Infigratinib)是一种口服的ATP竞争性泛FGFR酪氨酸激酶抑制剂（FGFR1：IC50 = 0.9nM；FGFR2：IC50 = 1.4nM；FGFR3：IC50 = 1nM；FGFR4：IC50 = 60nM）。
Cas No.:872511-34-7
Sample solution is provided at 25 µL, 10mM.
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BGJ398 (Infigratinib) is an oral, ATP-competitive pan-FGFR tyrosine kinase inhibitor (FGFR1: IC50 = 0.9nM; FGFR2: IC50 = 1.4nM; FGFR3: IC50 = 1nM; FGFR4: IC50 = 60nM) [1]. BGJ398 targets the fibroblast growth factor receptors FGFR1, FGFR2, FGFR3, and FGFR4, thereby blocking signal transduction mediated by these receptors and inhibiting FGFR-dependent tumor cell proliferation and angiogenesis [2-3]. BGJ398 is primarily used to treat dwarfism in children [4].
In SKOV3ip1 cells, the survival rate of cell in spheroid culture was significantly reduced after BGJ398 (0.3125-5µM; 72h) treatment [5]. In UMUC-14 cells, the combination of paclitaxel and BGJ398 (0-10µM; 72h) can produce a synergistic effect in promoting cell apoptosis [6].
In TMK-1 cells xenograft mice model, treatment with BGJ398 (10mg/kg; po; 20d) significantly inhibited tumor growth [7]. In Snu16R‑derived xenograft mice model, knockdown of BAG3 enhances the anti-tumor effect induced by BGJ398 (30mg/kg; po; 4 weeks) [8].
References:
[1]. Guagnano V, Furet P, Spanka C, et al. Discovery of 3-(2, 6-dichloro-3, 5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase[J]. Journal of medicinal chemistry, 2011, 54(20): 7066-7083.
[2]. Szymczyk J, Sluzalska K D, Materla I, et al. FGF/FGFR-dependent molecular mechanisms underlying anti-cancer drug resistance[J]. Cancers, 2021, 13(22): 5796.
[3]. Agrawal S, Maity S, AlRaawi Z, et al. Targeting drugs against fibroblast growth factor (s)-induced cell signaling[J]. Current drug targets, 2021, 22(2): 214-240.
[4]. Högler W, Ward L M. New developments in the management of achondroplasia[J]. Wiener Medizinische Wochenschrift, 2020, 170(5): 104-111.
[5]. Cha H J, Choi J H, Park I C, et al. Selective FGFR inhibitor BGJ398 inhibits phosphorylation of AKT and STAT3 and induces cytotoxicity in sphere-cultured ovarian cancer cells[J]. International Journal of Oncology, 2017, 50(4): 1279-1288.
[6]. Kim S H, Ryu H, Ock C Y, et al. BGJ398, a pan-FGFR inhibitor, overcomes paclitaxel resistance in urothelial carcinoma with FGFR1 overexpression[J]. International journal of molecular sciences, 2018, 19(10): 3164.
[7]. Schmidt K, Moser C, Hellerbrand C, et al. Targeting fibroblast growth factor receptor (FGFR) with BGJ398 in a gastric cancer model[J]. Anticancer Research, 2015, 35(12): 6655-6665.
[8]. Li K, Deng X, Feng G, et al. Knockdown of Bcl-2-associated athanogene-3 can enhance the efficacy of BGJ398 via suppressing migration and inducing apoptosis in gastric cancer[J]. Digestive Diseases and Sciences, 2021, 66(9): 3036-3044.
BGJ398 (Infigratinib)是一种口服的ATP竞争性泛FGFR酪氨酸激酶抑制剂（FGFR1：IC50 = 0.9nM；FGFR2：IC50 = 1.4nM；FGFR3：IC50 = 1nM；FGFR4：IC50 = 60nM） [1]。BGJ398靶向成纤维细胞生长因子受体FGFR1、FGFR2、FGFR3和FGFR4，从而阻断这些受体介导的信号转导，抑制FGFR依赖性的肿瘤细胞增殖和血管生成 [2-3]。BGJ398主要用于治疗儿童侏儒症 [4]。
在SKOV3ip1细胞中，BGJ398（0.3125-5µM；72h）处理后，球状培养细胞的存活率显著降低 [5]。在UMUC-14细胞中，paclitaxel与BGJ398（0-10µM；72h）联合应用可产生促进细胞凋亡的协同作用 [6]。
在TMK-1细胞异种移植小鼠模型中，BGJ398（10mg/kg；po；20d）治疗显著抑制肿瘤生长 [7]。在Snu16R衍生的异种移植小鼠模型中，BAG3的敲低增强了BGJ398（30mg/kg；po；4周）诱导的抗肿瘤作用 [8]。
| Cell experiment [1]: | |
Cell lines | SKOV3ip1 cells |
Preparation Method | To measure cell viability of spheroid cultures, SKOV3ip1 cells (5 × 104) were seeded in ultra-low attachment 24-well plates and incubated overnight. BGJ398 were then added, and the cells were incubated for an additional 72 hours. Cells were harvested from each well and transferred to a regular 24-well plate for an additional 12 hours. Attached, live cells were stained with 0.2% crystal violet solution for 20 minutes with gentle agitation. The stained cells were washed with distilled water. For colorimetric analysis, the crystal violet dye was extracted with 1% SDS/PBS, and absorbance was measured at 570nm using an EMax PLUS microplate reader. |
Reaction Conditions | 0.3125-5µM; 72h |
Applications | The survival rate of SKOV3ip1 cells in spheroid culture was significantly reduced after BGJ398 treatment. |
| Animal experiment [2]: | |
Animal models | TMK-1 cells xenograft mice model |
Preparation Method | Cancer cells (1 × 106) were injected subcutaneously into the right flank of 6- to 8-week-old athymic nude mice. Mice were randomly assigned to either a control or treatment group. When tumors reached approximately 80mm3, BGJ398 (10mg/kg, administered by oral gavage) was initiated. Tumor diameters were measured, and volumes were calculated (width2 × length × 0.5). Tumors were excised, weighed, and processed for subsequent experiments. |
Dosage form | 10mg/kg; po; 20d |
Applications | Treatment with BGJ398 significantly inhibited tumor growth. |
References: | |
| Cas No. | 872511-34-7 | SDF | |
| 别名 | FGFR抑制剂(NVP-BGJ398),BGJ398,BGJ-398,Infigratinib | ||
| 化学名 | 3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-[6-[4-(4-ethylpiperazin-1-yl)anilino]pyrimidin-4-yl]-1-methylurea | ||
| Canonical SMILES | CCN1CCN(CC1)C2=CC=C(C=C2)NC3=CC(=NC=N3)N(C)C(=O)NC4=C(C(=CC(=C4Cl)OC)OC)Cl | ||
| 分子式 | C26H31Cl2N7O3 | 分子量 | 560.48 |
| 溶解度 | ≥ 7mg/mL in DMSO with gentle warming | 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 | 1.7842 mL | 8.9209 mL | 17.8418 mL |
| 5 mM | 356.8 μL | 1.7842 mL | 3.5684 mL |
| 10 mM | 178.4 μL | 892.1 μL | 1.7842 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。
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Quality Control & SDS
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- Purity: >99.50%
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