Home Protein Tyrosine Kinase FGFR inhibitor - VEGFR inhibitor LY2874455

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LY2874455 FGFR inhibitor

Cat.No.S7057

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.
LY2874455 FGFR inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 444.31

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Quality Control

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
NCI-H1581 Antiproliferative assay 72 hrs Antiproliferative activity against FGFR1-amplified human NCI-H1581 cells after 72 hrs by CCK8/MTT assay, IC50<0.0005μM 27348537
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight 444.31 Formula

C21H19Cl2N5O2

 Storage (From the date of receipt)
CAS No. 1254473-64-7 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles CC(C1=C(C=NC=C1Cl)Cl)OC2=CC3=C(C=C2)NN=C3C=CC4=CN(N=C4)CCO

Solubility

In vitro
Batch:

DMSO : 88 mg/mL ( (198.05 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 88 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

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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.
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Mechanism of Action

Targets/IC50/Ki
FGFR2 [1]
(Cell-free assay)
2.6 nM
FGFR1 [1]
(Cell-free assay)
2.8 nM
FGFR4 [1]
(Cell-free assay)
6 nM
FGFR3 [1]
(Cell-free assay)
6.4 nM
VEGFR2 [1]
(Cell-free assay)
7 nM
In vitro
In RT-112 cells, HUVECs, KATO-III cells, and SNU-16 cells, LY2874455 inhibits FGF/FGFR-mediated signaling activities. This compound shows FGFR-dependent antiproliferative effects in KMS-11, OPM-2, SNU-16 and KATO-III cells. [1]
Kinase Assay
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.
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, this compound (3 mg/kg p.o.) results in dose-dependent inhibition of the tumor growth. [1]
References

Applications

Methods Biomarkers Images PMID
Western blot p-FRS2 / FRS2 / p-AKT / AKT / p-ERK / ERK / p-PLCγ1 / PLCγ1 MCL-1 S7057-WB1 30795553
Growth inhibition assay Cell death S7057-viability1 29408314

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03125239 Completed
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
Advanced Cancer
Eli Lilly and Company
 December 2010 Phase 1

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