FIIN-2 |
Catalog No.GC17323
One-Click Copy Product Info
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Irreversible inhibitor of FGFR
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1633044-56-0
Sample solution is provided at 25 µL, 10mM.
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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.
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. | |
| Cas No. | 1633044-56-0 | SDF | |
| Chemical Name | 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 | ||
| Formula | C35H38N8O4 | M.Wt | 634.73 |
| Solubility | ≥ 31.75mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.5755 mL | 7.8774 mL | 15.7547 mL |
| 5 mM | 315.1 μL | 1.5755 mL | 3.1509 mL |
| 10 mM | 157.5 μL | 787.7 μL | 1.5755 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 39 reference(s) in Google Scholar.)