| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
Purity: ≥98%
LY2874455 (LY-2874455; LY 2874455) is a novel and highly potent pan-FGFR inhibitor with potential anticancer activity. Its IC50 values are 2.8 nM, 2.6 nM, 6.4 nM, and 6 nM for FGFR1, FGFR2, FGFR3, and FGFR4 inhibition, respectively. It also has an IC50 of 7 nM for inhibiting VEGFR2 activity. In a number of cancer cell lines, LY2874455 demonstrates strong activity against FGF/FGFR-mediated signaling. In multiple tumor xenograft models representing the major FGF/FGFR relevant tumor histologies, such as bladder, stomach, and lung cancers as well as multiple myeloma, it exhibits excellent broad spectrum antitumor activity with a well-defined pharmacokinetic/pharmacodynamic relationship.
| Targets |
FGFR2 (IC50 = 2.6 nM); FGFR1 (IC50 = 2.8 nM); FGFR4 (IC50 = 6 nM); FGFR3 (IC50 = 6.4 nM); VEGFR2 (IC50 = 7 nM)
|
|
|---|---|---|
| ln Vitro |
|
|
| ln Vivo |
|
|
| Enzyme Assay |
The reaction mixtures included the following: 8 mM Tris-HCl (pH 7.5), 10 mM HEPES, 5 mM dithiothreitol, 10 μM ATP, 0.5 μCi 33P-ATP, 10 mM MnCl2, 150 mM NaCl, 0.01% Triton X-100, 4% DMSO, 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. The reaction mixtures were then incubated at room temperature for 30 minutes before being terminated with 10% H3PO4. After the reaction mixtures are moved to 96-well MAFB filter plates, they undergo three 0.5% H3PO4 washes. The plates are read using a Trilux reader once they have air-dried[1].
|
|
| Cell Assay |
The various cell lines for multiple myeloma cancer—KMS-11 and OPM-2 cells, L-363, and U266 cells—are employed. Two thousand cells per well are first grown in RPMI for six hours, and then LY2874455 is applied for three days at 37°C. After four hours of staining at 37°C, the cells are solubilized for one hour at the same temperature. Lastly, a plate reader reads the plate at 570 nm[1].
|
|
| Animal Protocol |
Mice: Mice (female, CD-1 nu/nu for RT-112, OPM-2, and NCI-H460 cells, and female, severe combined immunodeficient for SNU-16 cells) have their rear flanks subcutaneously implanted with a mixture of RT-112, OPM-2 (DSMZ), SNU-16, and NCI-H460 cells (RT-112: 2×106 per animal; OPM-2: 107 per animal; SNU-16: 106 per animal; and NCI-H460: 3×106 per animal) and Matrigel (1:1) mixed together. Solid tumors are grown by the implanted tumor cells. After tumors grow to a size of about 150 mm3, the animals are given oral doses of LY2874455 once (every day) or twice a day (TED90) at a dose of approximately 1 mg/kg (TED50) or 3 mg/kg (TED90) in 10% Acacia to test the drug's effectiveness in these models. Twice a week, the body weight and tumor volume are measured.
Rats: In each group of four male rats, LY2874455 (1, 3, and 10 mg/kg) is dosed on day 0 and the vehicle (1% hydroxyethylcellulose, 0.25% polysorbate 80, and 0.05% Dow Corning antifoam 1510-US in purified water) is administered on day 1. After vehicle administration on day 1, at least 120 minutes of control data are gathered. After the last animal is dosed on day 0, data are gathered for about 20 hours. |
|
| References |
| Molecular Formula |
C21H19CL2N5O2
|
|
|---|---|---|
| Molecular Weight |
444.31
|
|
| Exact Mass |
443.09
|
|
| Elemental Analysis |
C, 56.77; H, 4.31; Cl, 15.96; N, 15.76; O, 7.20
|
|
| CAS # |
1254473-64-7
|
|
| Related CAS # |
|
|
| Appearance |
Yellow solid powder
|
|
| SMILES |
C[C@H](C1=C(C=NC=C1Cl)Cl)OC2=CC3=C(C=C2)NN=C3/C=C/C4=CN(N=C4)CCO
|
|
| InChi Key |
GKJCVYLDJWTWQU-CXLRFSCWSA-N
|
|
| InChi Code |
InChI=1S/C21H19Cl2N5O2/c1-13(21-17(22)10-24-11-18(21)23)30-15-3-5-20-16(8-15)19(26-27-20)4-2-14-9-25-28(12-14)6-7-29/h2-5,8-13,29H,6-7H2,1H3,(H,26,27)/b4-2+/t13-/m1/s1
|
|
| Chemical Name |
2-[4-[(E)-2-[5-[(1R)-1-(3,5-dichloropyridin-4-yl)ethoxy]-1H-indazol-3-yl]ethenyl]pyrazol-1-yl]ethanol
|
|
| Synonyms |
LY 2874455; LY-2874455; LY2874455
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.63 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.63 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.63 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution. Solubility in Formulation 4: 2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2507 mL | 11.2534 mL | 22.5068 mL | |
| 5 mM | 0.4501 mL | 2.2507 mL | 4.5014 mL | |
| 10 mM | 0.2251 mL | 1.1253 mL | 2.2507 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| 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 | August 10, 2017 | Phase 1 |
Inhibition of FGF/FGFR- and VEGF/VEGFR2-mediated signaling activities in cells by LY2874455. Mol Cancer Ther. 2011 Nov;10(11):2200-10. |
Effects of LY2874455 on blood pressure in rats. Mol Cancer Ther. 2011 Nov;10(11):2200-10. |
Efficacy of LY2874455 in different tumor xenograft models. Mol Cancer Ther. 2011 Nov;10(11):2200-10. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
