FIIN-2
目录号 : GC17323
An FGFR inhibitor
Cas No.:1633044-56-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | TEL-FGFR2–transformed Ba/F3 cells are seeded in a 96-well plate and are treated with each concentration of the compounds. After 72 h the cells are assessed by MTS tetrazolium assay[1]. |
References: [1]. Tan L, et al. Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors. Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):E4869-4877. | |
FIIN-2 is an irreversible inhibitor of FGFR1–4 with IC50 values of 3.1, 4.3, 27, and 45 nM, respectively. FIIN-2 also moderately inhibited EGFR, with an IC50 of 204 nM. The Cys491 of FGFR2 is the primary labeled site for FIIN-2 binding [1].
FIIN-2 is the first class of inhibitors that can potently inhibit the proliferation of cells dependent upon the gatekeeper mutants of FGFR1 or FGFR2. The co-crystal structure of FGFR4 with FIIN-2 was reported, which unexpectedly exhibits a “DFG-out” covalent binding mode. FIIN-2 maintains the pyrimido[4,5-d] pyrimidinone core of FIIN-1 but removes the two chlorine atoms, which are crucial for FIIN-1's potency against FGFR. FIIN-2 maintains the ability to form a covalent bond with the P-loop cysteine but alter the selectivity profile versus other kinases. Compared with FIIN-1, FIIN-2 displayed strong binding to FGFRs and exhibited good overall kinase selectivity. FIIN-2 exhibited much less affinity for EGFR, but FIIN-3 potently bound to WT EGFR and to a subset of EGFR mutants. [1]
FIIN-2 inhibited proliferation of FGFR1-4 Ba/F3 cells with EC50s in the nanomolar range and were especially potent against FGFR2, with EC50s in the 1-nM range. FIIN-2 also inhibited the FGFR2 V564M gatekeeper mutant Ba/F3 cells, with EC50s of 58 nM, whereas FIIN-1 and BGJ398 had EC50s of over 1.0 μM against this mutant. FIIN-2 showed good potency against gatekeeper mutant V564F. In contrast, FIIN-2 was fourfold less potent (EC50 of 506 nM). FIIN-2 was inactive up to a concentration of 1.8 μM against EGFR L858R. FIIN-2 showed rather poor potency against protein kinase FLT1 (FLT1). In WT FGFR2 Ba/F3 cells, FIIN-2 completely inhibited the FGFR2 autophosphorylation on mutations of Tyr656/657 and V564M at concentrations of 3 nM and 300 nM, respectively. [1]
Reference:
1.Tan L, Wang J, Tanizaki J et al. Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors. Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):E4869-77. doi: 10.1073/pnas.1403438111. Epub 2014 Oct 27.
| Cas No. | 1633044-56-0 | SDF | |
| 化学名 | N-(4-((3-(3,5-dimethoxyphenyl)-7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidin-1(2H)-yl)methyl)phenyl)acrylamide | ||
| Canonical SMILES | O=C(C=C)NC1=CC=C(CN2C(N(C3=CC(OC)=CC(OC)=C3)CC4=CN=C(NC5=CC=C(N6CCN(C)CC6)C=C5)N=C42)=O)C=C1 | ||
| 分子式 | C35H38N8O4 | 分子量 | 634.73 |
| 溶解度 | ≥ 31.75mg/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 | 1.5755 mL | 7.8774 mL | 15.7547 mL |
| 5 mM | 0.3151 mL | 1.5755 mL | 3.1509 mL |
| 10 mM | 0.1575 mL | 0.7877 mL | 1.5755 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。