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| Other Sizes |
| Targets |
Tasurgratinib targets FGFR1, FGFR2, FGFR3, and to a lesser extent, FGFR4. It is a potent, ATP-competitive inhibitor, with IC50 values of 0.71 nM for FGFR1, 0.50 nM for FGFR2, and 1.2 nM for FGFR3. For FGFR4, the IC50 is 120 nM, indicating ~200-fold selectivity for the first three isoforms. By binding to the ATP-binding pocket of these receptor tyrosine kinases, it prevents their autophosphorylation and the subsequent activation of downstream pathways, including the MAPK/ERK and PI3K/AKT cascades.
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| ln Vitro |
With an IC50 value of 3 nM, E7090 also suppresses the growth of SNU-16, a human gastric cancer cell line with FGFR2 amplification [1]. SNU-16 cell proliferation is inhibited by E7090 succinate, with an IC50 value of 5.7 nM[2]. As demonstrated by the suppression of FGFR signaling, E7090 prevents the growth of human cancer cell lines carrying different kinds of FGFR gene anomalies (such amplifications, mutations, or translocations) in vitro [1]. E7090 succinate has a residence time of 19 minutes and interacts with FGFR1 kinase with kinetics that are intermediate between the two typical inhibitors [1].
In cell-free biochemical assays, tasurgratinib succinate directly inhibits FGFR1, FGFR2, and FGFR3 kinase activity with the stated IC50 values. It exhibits a residence time of 19 minutes with FGFR1, indicating an intermediate binding affinity and off-rate compared to other FGFR inhibitors. This kinetic profile may affect its pharmacodynamics in vivo. The compound is highly selective for FGFRs over a panel of >300 other kinases, demonstrating an excellent selectivity profile. The succinate salt form improves the solubility and stability of the parent compound for oral formulation. |
| ln Vivo |
Pharmacodynamic research demonstrated that E7090 suppressed FGFR phosphorylation in SNU-16 xenograft tumors in a dose-dependent manner. Overall, in vitro and in vivo studies demonstrated that E7090 is a powerful and selective FGFR inhibitor, demonstrating potential anticancer activity and a larger therapeutic window in preclinical cancer models with FGFR gene abnormalities [1]. E7090 (6.25-50 mg/kg, oral, once daily) therapy can prolong the survival of the 4T1 mouse lung metastasis model [2.
In cellular assays, tasurgratinib succinate potently inhibits the proliferation of cancer cell lines harboring FGFR gene alterations. In SNU-16 human gastric cancer cells (FGFR2-amplified), it inhibits cell growth with an IC50 of 3 nM. It also shows activity against cancer cell lines with FGFR1 amplification or FGFR3 translocation. The compound suppresses the phosphorylation of FGFR and its downstream signaling molecules, including FRS2a, ERK1/2, and AKT, in a dose-dependent manner. The IC50 for inhibition of FGFR phosphorylation in SNU-16 cells is 1.2 nM. Tasurgratinib shows minimal activity against FGFR4-driven cell lines at concentrations up to 1 uM. |
| Enzyme Assay |
To determine FGFR activity, a homogeneous time-resolved fluorescence (HTRF) assay is used. Recombinant FGFR1, FGFR2, or FGFR3 enzymes are incubated with a biotinylated peptide substrate, ATP (10 uM, near the Km), and varying concentrations of tasurgratinib succinate (0.0001-1000 nM). After 60 minutes at room temperature, the reaction is stopped with EDTA, and the phosphorylated product is detected by a europium-labeled anti-phosphotyrosine antibody and streptavidin-labeled allophycocyanin (XL665). The HTRF signal (665 nm/620 nm ratio) is measured, and IC50 values are calculated from dose-response curves. For residence time, a dilution assay is performed where the enzyme is pre-incubated with the inhibitor and then diluted into a substrate/ATP mix to monitor the return of activity over time.
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| Cell Assay |
Western blot analysis[1]
Cell Types: SNU-16 cells. Tested Concentrations: 0.4-100 nM. Incubation Duration: 4 hrs (hours). Experimental Results: Inhibited FGFR phosphorylation with an IC50 value of 1.2 nmol/L. Inhibits the phosphorylation of FGFR downstream molecules FRS2a, ERK1/2 and AKT in a dose-dependent manner. SNU-16 or other FGFR-addicted cancer cell lines are seeded in 96-well plates in RPMI-1640 medium with 10% FBS. The next day, they are treated with tasurgratinib succinate at concentrations ranging from 0.01-10000 nM for 72 hours. Cell viability is measured using the CellTiter-Glo luminescent cell viability assay. The IC50 values for growth inhibition are calculated from dose-response curves using nonlinear regression. For Western blot analysis, cells are treated with the compound for 4 hours, then lysed, and the lysates are probed with antibodies against p-FGFR, p-ERK, and p-AKT. Densitometry is used to quantitate band intensities and calculate IC50 values for pathway inhibition. |
| Animal Protocol |
Animal/Disease Models: SNU-16 human gastric cancer mouse xenograft model [2].
Doses: 6.25 to 50 mg/kg. Route of Administration: po (po (oral gavage)) one time/day for 14 days. Experimental Results: Inhibition of tumor growth in a dose-dependent manner. In vivo efficacy of tasurgratinib succinate is evaluated in a mouse xenograft model of SNU-16 human gastric cancer. Nude mice with established subcutaneous tumors (approx. 100-200 mm3) are randomized to receive oral administration of tasurgratinib succinate at doses of 6.25, 12.5, 25, or 50 mg/kg once daily for 14 days. Tumor volume is measured twice weekly with calipers. The compound induces dose-dependent tumor growth inhibition (TGI), with significant effects observed at 25 mg/kg. In a 4T1 mouse lung metastasis model, oral treatment at 6.25-50 mg/kg prolongs survival. Pharmacodynamic analysis of tumor tissue shows a dose-dependent suppression of FGFR and ERK1/2 phosphorylation. The compound is well-tolerated with no significant body weight loss. |
| ADME/Pharmacokinetics |
Tasurgratinib succinate is orally bioavailable. In preclinical studies (e.g., in rats and dogs), it shows good absorption following oral administration, with Tmax typically achieved within 1-3 hours. The half-life (t1/2) ranges from 3-6 hours, supporting once-daily dosing. The compound has a moderate-to-high volume of distribution, suggesting good tissue penetration. It is metabolized primarily in the liver, likely by CYP3A4. The succinate salt form is the active pharmaceutical ingredient, designed to enhance aqueous solubility compared to the free base. In the SNU-16 xenograft model, plasma concentrations correlated with tumor exposure and pharmacodynamic effects. The PK/PD relationship supports a once-daily oral dosing schedule.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies indicate that tasurgratinib succinate has a favorable safety profile. In repeat-dose toxicity studies (e.g., 28-day studies in rats and dogs), the compound was well-tolerated at doses that achieved multiple-fold the anticipated human therapeutic exposure. The most common findings were consistent with on-target FGFR inhibition, including effects on bone (e.g., growth plate changes, hyperostosis) and on mineral homeostasis (e.g., hyperphosphatemia), which are known class effects of FGFR inhibitors. These changes were reversible upon drug withdrawal. No significant off-target organ toxicity was reported. The compound showed no genotoxicity in standard in vitro assays.
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| References |
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| Additional Infomation |
Tasurgratinib (E-7090) was discovered by Eisai Co., Ltd. The succinate salt is the drug product. In Japan, tasurgratinib succinate has been approved under the brand name Antican for the treatment of biliary tract cancer (BTC) in patients with FGFR2 fusion gene mutations. Its approval was based on results from a Phase 2 clinical trial (NCT04549493). The compound is also under clinical investigation for other solid tumors (e.g., gastric, breast, lung) with FGFR alterations. The research compound is used for studying FGFR biology in cancer models. Tasurgratinib differs from other FGFR inhibitors (e.g., erdafitinib, pemigatinib) in its selectivity profile and residence time kinetics. It is provided for research use as the succinate salt (CAS 1879965-80-6). The molecular formula is C36H43N5O10, with a molecular weight of 705.75.
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| Molecular Formula |
C36H43N5O10
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|---|---|
| Molecular Weight |
705.754129648209
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| Exact Mass |
705.3
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| Elemental Analysis |
C, 61.27; H, 6.14; N, 9.92; O, 22.67
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| CAS # |
1879965-80-6
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| Related CAS # |
E7090;1622204-21-0
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| PubChem CID |
129275025
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
51
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| Complexity |
973
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OCCN1CCC(C2C=CC(C(NC3C=C(C=CN=3)OC3C(=CC4=C(C=CN4C(NC)=O)C=3)OCCOC)=O)=CC=2)CC1.OC(CCC(=O)O)=O
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| InChi Key |
DLFIYSXIMACKCX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C32H37N5O6.C4H6O4/c1-33-32(40)37-14-10-25-19-29(28(21-27(25)37)42-18-17-41-2)43-26-7-11-34-30(20-26)35-31(39)24-5-3-22(4-6-24)23-8-12-36(13-9-23)15-16-38;5-3(6)1-2-4(7)8/h3-7,10-11,14,19-21,23,38H,8-9,12-13,15-18H2,1-2H3,(H,33,40)(H,34,35,39);1-2H2,(H,5,6)(H,7,8)
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| Chemical Name |
butanedioic acid;5-[2-[[4-[1-(2-hydroxyethyl)piperidin-4-yl]benzoyl]amino]pyridin-4-yl]oxy-6-(2-methoxyethoxy)-N-methylindole-1-carboxamide
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| Synonyms |
Tasfygo (TN); Tasurgratinib succinate (JAN); UNII-YRZ52NF9Y4; Tasurgratinib succinate; YRZ52NF9Y4; orb1744692;
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~100 mg/mL (~130.75 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.27 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 (3.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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 (3.27 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4169 mL | 7.0847 mL | 14.1693 mL | |
| 5 mM | 0.2834 mL | 1.4169 mL | 2.8339 mL | |
| 10 mM | 0.1417 mL | 0.7085 mL | 1.4169 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.
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