LY2874455
LY2874455 (CAS 1254473-64-7) is a small molecule inhibitor targeting fibroblast growth factor receptors (FGFRs), proteins functioning through ligand-induced receptor dimerization and tyrosine kinase activation. By blocking FGFR phosphorylation and downstream signaling pathways, LY2874455 inhibits proliferation and migration in FGFR-dependent cancer cell models. LY2874455 shows inhibition of FGFR phosphorylation in FGFR1-, FGFR2-, and FGFR3-expressing cancer cell lines and xenografts, demonstrating antitumor efficacy across various FGFR-driven tumor types. It serves as a valuable tool molecule in oncology research investigating FGFR-mediated cancers.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 444.31 |
| Cas No. | 1254473-64-7 |
| Formula | C21H19Cl2N5O2 |
| Synonyms | LY 2874455; LY-2874455 |
| Solubility | ≥44.4 mg/mL in DMSO; insoluble in H2O; ≥6.34 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | 2-[4-[(E)-2-[5-[(1R)-1-(3,5-dichloropyridin-4-yl)ethoxy]-1H-indazol-3-yl]ethenyl]pyrazol-1-yl]ethanol |
| SDF | Download SDF |
| Canonical SMILES | CC(C1=C(C=NC=C1Cl)Cl)OC2=CC3=C(C=C2)NN=C3C=CC4=CN(N=C4)CCO |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
HUVECs and RT-112 cells, gastric cancer cell lines, SNU-16 and KATO-III |
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Preparation method |
The solubility of this compound in DMSO is >22.2mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
37°C, 1 hour |
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Applications |
LY2874455 potently inhibited the Erk phosphorylation induced by FGF2 and FGF9 in both HUVECs and RT-112 cell lines in a dose-dependent manner, with the IC50 values of 0.3 to 0.8 nmol/L. LY2874455 inhibited FGFR2 phosphorylation in SNU-16 and KATO-III cells, with estimated IC50 values of 0.8 and 1.5 nmol/L, respectively. LY2874455 inhibited the phosphorylation of FRS2, an immediate downstream target of FGFR in these cell lines, again with a similar potency of 0.8 to 1.5 nmol/L. |
| Animal experiment [1]: | |
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Animal models |
Mice xenografted with cancer cell lines with altered FGFR or FGF levels, RT-112 (overexpressing FGFR3), SNU-16 (amplified FGFR2), OPM-2 (overexpressing a mutant FGFR3), and NCI-H460 (a high level of FGF2) |
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Dosage form |
1 mg/kg, 3 mg/kg, every day |
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Application |
LY2874455 exhibited a rapid, robust, dose-dependent inhibition of tumor growth in all 4 models tested. LY2874455 caused a significant regression of tumor growth in the RT-112, SNU-16, and OPM-2 tumor models, especially when dosed at 3 mg/kg twice a daily. |
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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]. Zhao G, Li W, Chen D, et al. A novel, selective inhibitor of fibroblast growth factor receptors that shows a potent broad spectrum of antitumor activity in several tumor xenograft models[J]. Molecular cancer therapeutics, 2011, 10(11): 2200-2210. |
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| Description | LY2874455 is a potent, selective, small-molecule inhibitor of fibroblast growth factor receptors (FGFR) with IC50 values of 2.8, 2.6, 6.4 and 6 nM for FGFR1, 2, 3, and 4, respectively. | |||||
| Targets | FGFR1 | FGFR2 | FGFR3 | FGFR4 | ||
| IC50 | 2.8 nM | 2.6 nM | 6.4 nM | 6 nM | ||
Quality Control & MSDS
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Chemical structure
