| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
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Purity: ≥98%
ASP5878 is a novel, potent, selective and orally bioactive inhibitor of FGFR 1, 2, 3, and 4, with IC50 values of 0.47 nM, 0.6 nM, 0.74 nM and 3.5 nM for FGFR 1, 2, 3, and 4 kinase activity. Potential antineoplastic activity exists for ASP5878. FGFR3-dependent urothelial cancer can be treated with ASP5878 either with or without chemoresistance. For patients with hepatocellular carcinoma whose tumors express fibroblast growth factor 19, ASP5878 is a potentially useful therapeutic agent.
| Targets |
FGFR1 (IC50 = 0.47 nM); FGFR2 (IC50 = 0.6 nM); FGFR3 (IC50 = 0.74 nM); FGFR4 (IC50 = 3.5 nM)
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|---|---|
| ln Vitro |
Most HCC cell lines have strong anti-apoptotic action from ASP5878 [1]. In humans, ASP5878 suppresses FGFR4 phosphorylation in a way dependent on concentration. FRS2 mobility is altered, phosphorylation is inhibited, and ERK phosphorylation is inhibited as a result of ASP5878 administration [1].
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| ln Vivo |
In Hep3B2.1-7 subcutaneous xenograft and HCC orthotopic xenograft models, ASP5878 (3 mg/kg, bridge, once daily) showed antitumor activity [1]. In HCC, ASP5878 induces FGF19 contraction and expression.
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| Cell Assay |
Cell viability assay [1]
Cell Types: Human liver cancer cell line. Tested Concentrations: 0-1000 nM. Incubation Duration: 5 days. Experimental Results: HuH-7, Hep3B2.1-7 and JHH-7 cell lines demonstrated strong sensitivity to ASP5878, with IC50 values of 27, 8.5 and 21 nmol/L respectively. At 1000 nM, the growth inhibition rate of HLF was 64%, and the growth inhibition rate of other ASP5878-sensitive cell lines was higher than 95%. |
| Animal Protocol |
Animal/Disease Models: HCC orthotopic xenograft model (mouse) [1].
Doses: 3 mg/kg. Route of Administration: po (po (oral gavage)) one time/day for 24 days. Experimental Results: Mice treated with vehicle and sorafenib demonstrated lower tumor burden compared to vehicle. Induces sustained tumor regression without tumor regrowth. |
| References | |
| Additional Infomation |
FGFR Inhibitor ASP5878 is an orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR), with potential antineoplastic activity. Upon oral administration, FGFR inhibitor ASP5878 binds to and inhibits FGFR, which results in the inhibition of FGFR-mediated signal transduction pathways. This inhibits proliferation in FGFR-overexpressing tumor cells. FGFR, a family of receptor tyrosine kinases upregulated in many tumor cell types, plays a key role in cellular proliferation and survival.
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| Molecular Formula |
C18H19F2N5O4
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|---|---|
| Molecular Weight |
407.37137055397
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| Exact Mass |
407.14
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| Elemental Analysis |
C, 53.07; H, 4.70; F, 9.33; N, 17.19; O, 15.71
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| CAS # |
1453208-66-6
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| Related CAS # |
1453208-66-6;ASP5878 HCl;
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| PubChem CID |
71736582
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
1.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
29
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| Complexity |
473
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
VDZZYOJYLLNBTD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H19F2N5O4/c1-27-14-5-15(28-2)17(20)13(16(14)19)10-29-12-7-21-18(22-8-12)24-11-6-23-25(9-11)3-4-26/h5-9,26H,3-4,10H2,1-2H3,(H,21,22,24)
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| Chemical Name |
2-[4-[[5-[(2,6-difluoro-3,5-dimethoxyphenyl)methoxy]pyrimidin-2-yl]amino]pyrazol-1-yl]ethanol
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| Synonyms |
ASP5878; ASP-5878; ASP 5878
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: ~81 mg/mL (~198.8 mM)
Ethanol: ~4 mg/mL (~9.8 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.11 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 20.8 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: ≥ 2.08 mg/mL (5.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4548 mL | 12.2739 mL | 24.5477 mL | |
| 5 mM | 0.4910 mL | 2.4548 mL | 4.9095 mL | |
| 10 mM | 0.2455 mL | 1.2274 mL | 2.4548 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 |
| NCT02038673 | Completed | Drug: ASP5878 | Solid Tumors | Astellas Pharma Inc | November 5, 2013 | Phase 1 |
 Antiproliferative effect of ASP5878 in FGF19-expressing HCC cell lines.Mol Cancer Ther.2017 Jan;16(1):68-75. |
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 ASP5878 treatment leads to tumor regression in FGF19-expressing Hep3B2.Mol Cancer Ther.2017 Jan;16(1):68-75. |
 ASP5878 treatment leads to tumor regression in FGF19-expressing HuH-7 HCC orthotropic graft model.
Antitumor activity of ASP5878, poorly responsive to sorafenib, in the Hep3B2.Mol Cancer Ther.2017 Jan;16(1):68-75. |
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