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LY2874455

Name: LY2874455
Brand: Selleck Chemicals
SKU: S7057
Rating: 5 (9 reviews)

Catalog No.S7057

For research use only.

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.

CAS No. 1254473-64-7

Selleck's LY2874455 has been cited by 9 Publications

1 Customer Review

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FGFR Signaling Pathway Map

Biological Activity

Description

Targets

FGFR2 ^[1] (Cell-free assay)	FGFR1 ^[1] (Cell-free assay)	FGFR4 ^[1] (Cell-free assay)	FGFR3 ^[1] (Cell-free assay)	VEGFR2 ^[1] (Cell-free assay)
2.6 nM	2.8 nM	6 nM	6.4 nM	7 nM

In vitro

In RT-112 cells, HUVECs, KATO-III cells, and SNU-16 cells, LY2874455 inhibits FGF/FGFR-mediated signaling activities. LY2874455 shows FGFR-dependent antiproliferative effects in KMS-11, OPM-2, SNU-16 and KATO-III cells. ^[1]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

NCI-H1581	NVjkeZlZSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		MUO3NkBpenN?		MXfBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IF\HSnIyNWGvcHzp[olm\CCqdX3hckBPS0lvSEG1PFEh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IFPDT\|gwVVSWIHHzd4F6NCCLQ{WwQFAvODByNd88US=>	M4jteVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5M{S4OVM4Lz5{N{O0PFU{PzxxYU6=

Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID

Western blot	p-FRS2 / FRS2 / p-AKT / AKT / p-ERK / ERK / p-PLCγ1 / PLCγ1 ; MCL-1	30795553 29408314
Growth inhibition assay	Cell death	29408314

In vivo

LY2874455 exhibits a potent inhibition of FGF-induced Erk phosphorylation in the heart tissues of mice with TED50 and TED90 values of 1.3 and 3.2 mg/kg, respectively. In mice bearing RT-112, OPM-2 (DSMZ), SNU-16, or NCI-H460 xenograft, LY2874455 (3 mg/kg p.o.) results in dose-dependent inhibition of the tumor growth. ^[1]

Protocol (from reference)

Kinase Assay: ^[1]	Biochemical filter-binding assays for detection of FGFR phosphorylation activities : Reaction mixtures contains 8 mM Tris-HCl (pH 7.5), 10 mmol/L HEPES, 5 mM dithiothreitol, 10 μM ATP, 0.5 μCi ³³P-ATP, 10 mM MnCl₂, 150 mM NaCl, 0.01% Triton X-100, 4% dimethyl sulfoxide, 0.05 mg/mL poly(Glu:Tyr) (4:1, average molecular weight of 20–50 kDa), and 7.5, 7.5, and 16 ng of FGFR1, FGFR3, and FGFR4, respectively, and are incubated at room temperature for 30 minutes followed by termination with 10% H₃PO₄. The reaction mixtures are transferred to 96-well MAFB filter plates that are washed 3 times with 0.5% H₃PO₄. After air-drying, the plates are read with a Trilux reader.
Cell Research: ^[1]	Cell lines: KMS-11, OPM-2, L-363, U266, SNU-16, KATO-III, NUGC-3 and SH-10-TC cells Concentrations: ~1 μM Incubation Time: 72 hours Method: Cells (2,000 per well) are first grown in RPMI for 6 hours and treated with LY2874455 at 37 ℃ for 3 days. The cells are stained at 37℃ for 4 hours and then solubilized at 37℃ for 1 hour. Finally, the plate is read at 570 nm using a plate reader (Spectra Max Gemini XS).
Animal Research: ^[1]	Animal Models: Mice bearing RT-112, OPM-2 (DSMZ), SNU-16, or NCI-H460 xenograft Dosages: 3 mg/kg Administration: p.o.

References

[1] Zhao G, et al. Mol Cancer Ther. 2011, 10(11), 2200-2210.

Solubility (25°C)

In vitro	DMSO	88 mg/mL (198.05 mM)
	Ethanol	57 mg/mL warmed (128.28 mM)
	Water	Insoluble
In vivo	Add solvents to the product individually and in order (Data is from Selleck tests instead of citations): 2% DMSO+30% PEG 300+5% Tween 80+ddH2O For best results, use promptly after mixing. Click to purchase: PEG300 Tween 80	5mg/mL

Chemical Information

Molecular Weight	444.31
Formula	C₂₁H₁₉Cl₂N₅O₂
CAS No.	1254473-64-7
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	CC(C1=C(C=NC=C1Cl)Cl)OC2=CC3=C(C=C2)NN=C3C=CC4=CN(N=C4)CCO

Download LY2874455 SDF

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

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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 ddH₂O, 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.

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03125239	Completed	Drug: Merestinib\|Drug: LY2874455	Relapsed Adult Acute Myeloid Leukemia\|Refractory Adult Acute Myeloid Leukemia	Jacqueline Garcia MD\|Eli Lilly and Company\|Dana-Farber Cancer Institute	August 10 2017	Phase 1
NCT01212107	Completed	Drug: FGF Receptor\|Drug: Phosphate Binders	Advanced Cancer	Eli Lilly and Company	December 2010	Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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