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Chemical Structure| 1254473-64-7 Chemical Structure| 1254473-64-7

Structure of LY2874455
CAS No.: 1254473-64-7

Chemical Structure| 1254473-64-7

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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.

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Product Details of LY2874455

CAS No. :1254473-64-7
Formula : C21H19Cl2N5O2
M.W : 444.31
SMILES Code : OCCN1N=CC(/C=C/C2=NNC3=C2C=C(O[C@@H](C4=C(Cl)C=NC=C4Cl)C)C=C3)=C1
MDL No. :MFCD22124884
InChI Key :GKJCVYLDJWTWQU-CXLRFSCWSA-N
Pubchem ID :46944259

Safety of LY2874455

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of LY2874455

RTK

Isoform Comparison

Biological Activity

Target
  • VEGFR2

    VEGFR2, IC50:7 nM

  • FGFR2

    FGFR2, IC50:2.6 nM

  • FGFR3

    FGFR3, IC50:6.4 nM

  • FGFR4

    FGFR4, IC50:6 nM

  • FGFR1

    FGFR1, IC50:2.8 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
RMS559 cells 100 nM 1 h Inhibition of FGFR4 V550L signaling PMC9681859
RMS559 cells 10 nM 72 h Inhibition of cell viability PMC9681859
H1703 40 nM 1 h To evaluate the effect of LY2874455 on carbon ion radiosensitivity, results showed SER of 1.20±0.18 PMC6770837
H1299 40 nM 1 h To evaluate the effect of LY2874455 on carbon ion radiosensitivity, results showed SER of 1.27±0.09 PMC6770837
A549 40 nM 1 h To evaluate the effect of LY2874455 on carbon ion radiosensitivity, results showed SER of 1.66±0.17 PMC6770837
H1299 cells 100 nM 1 h pre-irradiation to 10 days post-irradiation Evaluate the radiosensitizing effect of LY2874455 on H1299 cells, results showed 100 nM LY2874455 increased the sensitivity of H1299 cells to X-rays by 53% PMC9179643
A549 cells 100 nM 1 h pre-irradiation to 10 days post-irradiation Evaluate the radiosensitizing effect of LY2874455 on A549 cells, results showed 100 nM LY2874455 increased the sensitivity of A549 cells to X-rays by 62% PMC9179643
H1703 cells 100 nM 1 h pre-irradiation to 10 days post-irradiation Evaluate the radiosensitizing effect of LY2874455 on H1703 cells, results showed 100 nM LY2874455 increased the sensitivity of H1703 cells to X-rays by 31% PMC9179643
KMBC cells 5 μM 24 hours To evaluate the effect of LY2874455 on cell death in KMBC cells, results showed that LY2874455 induced non-apoptotic cell death. PMC5960421
KMCH cells 5 μM 24 hours To evaluate the effect of LY2874455 on cell death in KMCH cells, results showed that LY2874455 induced non-apoptotic cell death. PMC5960421
NRH-LS1 cells 100 nM 72 hours LY2874455 completely inhibited the growth of NRH-LS1 cells after 72 hours PMC6406403
HCC827 cells 10 nM 72 hours To evaluate the inhibitory effect of LY2874455 in combination with gefitinib on the proliferation of HCC827 cells. Results showed that LY2874455 significantly reduced the IC50 of gefitinib, effectively reversing gefitinib resistance induced by FGF3/4/19/CCND1 overexpression. PMC9260114
PC-9 cells 10 nM 72 hours To evaluate the inhibitory effect of LY2874455 in combination with gefitinib on the proliferation of PC-9 cells. Results showed that LY2874455 significantly reduced the IC50 of gefitinib, effectively reversing gefitinib resistance induced by FGF3/4/19/CCND1 overexpression. PMC9260114
Entamoeba invadens trophozoites 1.40 μM (EC50) 72 hours Evaluate the inhibitory effect of LY2874455 on Entamoeba invadens trophozoites, showing micromolar potency. PMC8846492
Entamoeba histolytica trophozoites 0.31 μM (EC50) 72 hours Evaluate the inhibitory effect of LY2874455 on Entamoeba histolytica trophozoites, showing submicromolar potency. PMC8846492
LPS853 cells 100 nM 96 hours LY2874455 showed modest growth inhibition in LPS853 cells PMC6406403
LPS510 cells 100 nM 96 hours LY2874455 induced apoptosis in LPS510 cells after 96 hours PMC6406403
NRH-LS1 cells 100 nM 96 hours LY2874455 induced apoptosis in NRH-LS1 cells after 96 hours PMC6406403

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NOD/SCID mice Patient-derived xenograft (PDX) model Oral gavage 3 mg/kg Twice daily for 7 days To evaluate the antitumor effect of LY2874455 in the PDX model, results showed that LY2874455 treatment resulted in reduced tumor weight, accompanied by decreased MCL1 expression and cell necrosis. PMC5960421
BALB/c female nude mice A549 xenograft model Oral 3 mg/kg Once daily for 7 consecutive days Evaluate the radiosensitizing effect of LY2874455 on A549 xenograft model, results showed combination treatment significantly suppressed tumor growth without noticeable toxicity PMC9179643
NOD-scid IL2rγnull (NSG) mice LS70x xenograft model Oral gavage 3 mg/kg Twice daily for 28 days LY2874455 significantly inhibited tumor growth in the LS70x xenograft model PMC6406403
BALB/c nude mice PC-9-4X cell xenograft model Oral administration 3 mg/kg LY2874455, 100 mg/kg gefitinib, 50 mg/kg abemaciclib Twice a week for 12 days To evaluate the inhibitory effect of LY2874455 in combination with gefitinib and abemaciclib on the growth of PC-9-4X xenograft tumors. Results showed that the combination therapy significantly inhibited tumor growth, reduced tumor weight, and decreased Ki67 expression. PMC9260114
Female athymic nude mice RMS559 xenograft model Oral 6 mg/kg Twice daily (weekdays), once daily (weekends), total of 25 treatments LY2874455 showed poor efficacy in inhibiting tumor growth in vivo PMC9681859

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.25mL

0.45mL

0.23mL

11.25mL

2.25mL

1.13mL

22.51mL

4.50mL

2.25mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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