LY 2874455
Description- Product Name
- LY 2874455
- CAS No.
- 1254473-64-7
- Chemical Name
- LY 2874455
- Synonyms
- CS-650;EOS-62114;LY 2874455;LY2874455 98%;LY2874455 ，S7057;LY2874455/LY-2874455;LY 2874455 USP/EP/BP;LY2874455, 10 mM in DMSO;LY2874455, FGF/FGFR inhibitor;LY 2874455; LY-2874455;LY2874455
- CBNumber
- CB12616026
- Molecular Formula
- C21H19Cl2N5O2
- Formula Weight
- 444.31
- MOL File
- 1254473-64-7.mol
LY 2874455 Property
- Boiling point:
- 672.6±55.0 °C(Predicted)
- Density
- 1.44
- storage temp.
- Store at -20°C
- solubility
- ≥44.4 mg/mL in DMSO; insoluble in H2O; ≥6.34 mg/mL in EtOH with gentle warming and ultrasonic
- form
- solid
- pka
- 12.93±0.40(Predicted)
- color
- Pink to gray
- CAS DataBase Reference
- 1254473-64-7
Hazard and Precautionary Statements (GHS)
- Symbol(GHS)
-
- Signal word
- Warning
- Hazard statements
-
H302Harmful if swallowed
H315Causes skin irritation
H319Causes serious eye irritation
H335May cause respiratory irritation
- Precautionary statements
-
P261Avoid breathing dust/fume/gas/mist/vapours/spray.
P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.
N-Bromosuccinimide Price
- Product number
- 20843
- Product name
- LY2874455
- Purity
- ≥98%
- Packaging
- 1mg
- Price
- $74
- Updated
- 2024/03/01
- Product number
- 20843
- Product name
- LY2874455
- Purity
- ≥98%
- Packaging
- 5mg
- Price
- $220
- Updated
- 2024/03/01
- Product number
- 20843
- Product name
- LY2874455
- Purity
- ≥98%
- Packaging
- 10mg
- Price
- $330
- Updated
- 2024/03/01
- Product number
- 20843
- Product name
- LY2874455
- Purity
- ≥98%
- Packaging
- 25mg
- Price
- $437
- Updated
- 2024/03/01
- Product number
- L486580
- Product name
- LY2874455
- Packaging
- 25mg
- Price
- $365
- Updated
- 2021/12/16
LY 2874455 Chemical Properties,Usage,Production
Description
LY2874455 is a pan-FGFR inhibitor with IC50 of 2.8 nM, 2.6 nM, 6.4 nM, and 6 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively, and also inhibits VEGFR2 activity with IC50 of 7 nM. Phase 1.
Uses
LY 2874455 is a pan-FGFR inhibitor which remain the focus of research for use in lung and bladder cancers.
Biological Activity
ly2874455 is a novel and potent fgfr inhibitor with ic50 value of 7 nm [1].fibroblast growth factor receptors (fgfrs) are receptors bind ligand of fgf family, which have a intracellular domain with tyrosine kinase activity. the binding of fgf triggers receptor dimerization and thus the activation of tyrosine kinase activity. activated tyrosine kinase phosphorylates various downstream factors to induce downstream signaling, including fgf substrate 2 (fgs2). this signaling pathway contributes to fgfr-mediated cell proliferation and migration, which are involved in tumor formation and progression.in huvecs cell line expressing fgfr1 and rt-112 cell line expressing fgfr3, ly2874455 treatment resulted in inhibition of fgf2 and fgf9 induced erk phosphorylation, which indicated the inhibitory activity of ly2874455 for fgfr1 and fgfr3 [1]. in snu-16 and kato-ш cell line, the inhibition of fgfr2 phosphorylation was also observed, which indicated a direct inhibition by ly2874455 [2]. additionally, when several multiple myeloma cancer cell lines were treated with lys2874455, the cell lines with chromosomal translocation that resulted in overexpression of fgfr3 were significantly more susceptible to the inhibition of ly2874455 [2]. it suggested fgfr was the specific target of ly2874455 inhibition.in rt-112, snu-16, opm-2 and nci-h460 xenograft tumor model, treatment of ly2874455 twice a day (1.5 mg/kg and 3 mg/kg) resulted in significant dose-dependent reduction of cellular level of phosphorylated fgfr, and also regression of tumor growth. it indicated the inhibitory activity of ly2874455 in vivo [2].
Synthesis
1254473-82-9
1254473-64-7
Methanol (57 mL) was added to a 250 mL three-necked round-bottomed flask equipped with a dosing funnel, nitrogen inlet, internal temperature probe and magnetic stirrer and cooled in an ice bath. Acetyl chloride (20 mL, 281.03 mmol) was added slowly and dropwise to the resulting solution through the addition funnel. Subsequently, 5-((R)-1-(3,5-dichloropyridin-4-yl)ethoxy)-1-(tetrahydro-2H-pyran-2-yl)-3-((E)-2-(1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazol-4-yl)vinyl)-1H-indazole (7.1 g, 11.59 mmol) solution in methanol (40 mL). After completion of addition, the ice bath was removed and the reaction mixture was warmed to room temperature and stirred for 4 hours. Upon completion of the reaction, the mixture was concentrated under vacuum to give a yellow foamy substance. The foam was dissolved in methanol (10 mL) and saturated aqueous sodium bicarbonate solution (120 mL) was slowly added. After stirring for 30 minutes at room temperature, the mixture was filtered, the solid was washed with water (100 mL) and dried under vacuum. Recrystallization by hot ethyl acetate/methanol/hexane mixed solvent afforded the title compound (R,E)-2-(4-(2-(2-(5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazol-3-yl)vinyl)-1H-pyrazol-1-yl)ethanol as a white solid in 2.1 g yield (41% yield). Mass spectrum (electrospray ionization) m/z 444 [M + 1]+.
in vivo
LY2874455 demonstrated rapid, robust, and dose-dependent tumour growth inhibition across all four tested models. Importantly, this compound induced significant tumour regression in RT-112, SNU-16 and OPM-2 models, particularly at a dose of 3 mg/kg administered twice daily. Furthermore, LY2874455 demonstrated favourable pharmacokinetic properties at TED50 and TED90 concentrations (1 and 3 mg/kg). When tested in the RT-112 tumour xenograft model under intermittent dosing regimens (twice daily for one week followed by one week off, or twice daily for two days followed by two days off), LY2874455 also proved effective. When administered to rats at doses of 1 and 3 mg/kg, LY2874455 exhibited IVTI values 2.6-fold and 7.7-fold higher than TED50 (0.39 mg/kg) in the rat cardiac IVTI assay, respectively, with no significant changes in blood pressure observed. However, when administered at 10 mg/kg (25.6 times higher than TED₅₀ ), a significant increase in arterial pressure was observed in rats[1]。
target
FGFR1
IC 50
FGFR1: 2.8 nM (IC50); FGFR2: 2.6 nM (IC50); FGFR3: 6.4 nM (IC50); FGFR4: 6 nM (IC50)
References
[1] zhao, g s 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. molecular cancer therapeutics. 2011, 10(11): 2200-2210.
LY 2874455 Preparation Products And Raw materials
Raw materials
Preparation Products
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View Lastest Price from LY 2874455 manufacturers
- Product
- LY 2874455 1254473-64-7
- Price
- US $2.00/kg
- Min. Order
- 1kg
- Purity
- 99%
- Supply Ability
- 100kg
- Release date
- 2018-12-24