| Size | Price | Stock | Qty |
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| Other Sizes |
| Targets |
The primary targets of Tasurgratinib are the fibroblast growth factor receptors FGFR1, FGFR2, and FGFR3. FGFRs are receptor tyrosine kinases that are activated upon binding to their ligands, the fibroblast growth factors (FGFs). This activation triggers downstream signaling pathways, including the RAS-MAPK, PI3K-AKT, and STAT pathways, which regulate fundamental cellular processes. Aberrant FGFR signaling is a well-established oncogenic driver in various cancers, including bladder, breast, gastric, and lung cancers, often through gene amplifications, activating mutations, or chromosomal translocations. By potently inhibiting FGFR1-3, Tasurgratinib blocks this oncogenic signaling, leading to the inhibition of cancer cell proliferation and survival. Its weak inhibition of FGFR4 suggests it is a highly selective inhibitor for the FGFR1-3 subtypes.
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| ln Vitro |
SNU-16, a human gastric cancer cell line with FGFR2 amplification, is inhibited by E7090 at an IC50 value of 3 nM[1]. With an IC50 value of 5.7 nM, E7090 suppresses the growth of SNU-16 cells[2]. E7090 suppresses FGFR signaling, which shows that it prevents human cancer cell lines with different FGFR gene abnormalities (such as amplifications, mutations, or translocations) from proliferating in vitro [1]. E7090 succinate has a residence duration of 19 minutes and interacts with FGFR1 kinase in an intermediate manner compared to two typical inhibitors [1].
Tasurgratinib is a highly potent inhibitor of FGFR1, FGFR2, and FGFR3, with IC₅₀ values in the sub-nanomolar to low nanomolar range (0.71, 0.50, and 1.2 nM, respectively). This indicates it is an extremely effective inhibitor at very low concentrations. Its selectivity is demonstrated by its much weaker inhibition of FGFR4 (IC₅₀ = 120 nM). In vitro, Tasurgratinib shows selective antiproliferative activity against cancer cell lines that harbor FGFR genetic alterations, such as amplifications or mutations, but not against cell lines with normal FGFR signaling. This confirms its on-target activity and highlights its potential as a targeted therapy. |
| ln Vivo |
E7090 reduced FGFR phosphorylation in SNU-16 xenograft tumors in a dose-dependent manner, according to pharmacodynamic study [1]. The oral administration of E7090 (6.25-50 mg/kg, once day) has been shown to extend the longevity of the 4T1 mouse lung metastasis model [2].
Tasurgratinib has demonstrated significant in vivo antitumor activity. In a mouse xenograft model of SNU-16 human gastric cancer, which harbors an FGFR2 amplification, Tasurgratinib exhibited antitumor activity and inhibited FGFR signaling. This in vivo validation is crucial for demonstrating that the compound's potent in vitro activity translates into a meaningful therapeutic effect in a living organism. Its oral availability is a key feature for a potential cancer therapeutic. |
| Enzyme Assay |
The in vitro kinase assay for Tasurgratinib measures its ability to inhibit the kinase activity of FGFR1, FGFR2, FGFR3, and FGFR4. In these assays, purified recombinant FGFR kinases are incubated with a peptide substrate and ATP. The transfer of a phosphate group from ATP to the substrate is measured, typically using a radioactive or fluorescence-based method. The assay is performed in the presence of varying concentrations of Tasurgratinib. A control without the inhibitor defines 100% enzyme activity. By plotting the percent inhibition versus the compound concentration, the IC₅₀ values for each FGFR subtype can be determined.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: SNU-16 Cell Tested Concentrations: 0.4-100 nM Incubation Duration: 4 hrs (hours) Experimental Results: Inhibits FGFR phosphorylation with an IC50 value of 1.2 nM. Inhibits the phosphorylation of FGFR downstream molecules FRS2a, ERK1/2 and AKT in a dose-dependent manner. In vitro cell-based assays for Tasurgratinib evaluate its antiproliferative and signaling inhibitory effects in cancer cells. A panel of cancer cell lines with known FGFR status (e.g., FGFR-amplified, FGFR-mutant, or FGFR wild-type) is treated with varying concentrations of Tasurgratinib. Cell viability is assessed after 72-96 hours using a standard assay like CellTiter-Glo. The compound's selective activity against FGFR-driven cell lines is a key finding. Additionally, the inhibition of FGFR signaling is confirmed by Western blotting for phosphorylated FGFR and downstream signaling proteins like ERK and AKT. |
| Animal Protocol |
Animal/Disease Models: SNU-16 human gastric cancer mouse xenograft model [2]
Doses: 6.25 to 50 mg/kg Route of Administration: Orally, one time/day for 14 days Experimental Results: Inhibited tumor growth in a dose-dependent manner. In vivo animal studies for Tasurgratinib have been conducted in mouse xenograft models. In a typical study, immunocompromised mice are implanted with a human cancer cell line that is driven by FGFR signaling (e.g., SNU-16 gastric cancer cells, which have FGFR2 amplification). Once tumors reach a certain size, the mice are randomized into treatment groups, including a vehicle control group and groups receiving Tasurgratinib at various doses. The compound is administered orally, typically daily. Tumor volumes are measured regularly. At the end of the study, tumors are harvested for analysis of FGFR signaling inhibition. These studies demonstrate the in vivo efficacy of the compound. |
| ADME/Pharmacokinetics |
Tasurgratinib is characterized as an orally available compound. Its molecular weight is 587.67. Detailed pharmacokinetic parameters such as half-life, Cmax, and bioavailability are not provided in the search results but would be determined in preclinical studies. Its oral availability is a key feature for a cancer therapeutic, allowing for convenient administration.
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| Toxicity/Toxicokinetics |
Specific toxicity data for Tasurgratinib is not detailed in the provided search results. As a kinase inhibitor, its selectivity for FGFR1-3 over other kinases is a key determinant of its toxicity profile. Its weak inhibition of FGFR4 suggests it may spare the liver, as FGFR4 is important for bile acid metabolism. It is classified as a research compound and is not intended for human use.
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| References |
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| Additional Infomation |
Tasurgratinib is an inhibitor of the fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) pathway with potential antitumor activity. Upon administration, Tasurgratinib selectively interferes with the binding of FGF to FGFR through a mechanism not yet fully elucidated. This inhibits FGFR-mediated signaling, leading to suppressed proliferation and cell death in FGFR-overexpressing tumor cells. FGFR is a receptor tyrosine kinase crucial for tumor cell proliferation, differentiation, and survival; its expression is upregulated in various tumor cell types.
Tasurgratinib (E-7090) is a promising investigational drug for the treatment of cancers driven by FGFR1, FGFR2, or FGFR3 alterations. Its high potency, selectivity, and oral availability make it an attractive candidate for clinical development. The compound has been investigated in clinical trials for FGFR-driven cancers, and as of the latest information, it may have received regulatory approval in some regions. |
| Molecular Formula |
C32H37N5O6
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|---|---|
| Molecular Weight |
587.666087865829
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| Exact Mass |
587.274
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| Elemental Analysis |
C, 65.40; H, 6.35; N, 11.92; O, 16.33
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| CAS # |
1622204-21-0
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| Related CAS # |
E7090 succinate;1879965-80-6
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| PubChem CID |
78323434
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.634
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| LogP |
2.05
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
43
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| Complexity |
880
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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
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| InChi Key |
IBHOLSBDZMIPPT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C32H37N5O6/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/h3-7,10-11,14,19-21,23,38H,8-9,12-13,15-18H2,1-2H3,(H,33,40)(H,34,35,39)
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| Chemical Name |
5-((2-(4-(1-(2-hydroxyethyl)piperidin-4-yl)benzamido)pyridin-4-yl)oxy)-6-(2-methoxyethoxy)-N-methyl-1H-indole-1-carboxamide
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| Synonyms |
E7090; E 7090; E-7,090; tasurgratinib; TN7CUD1NGA; UNII-TN7CUD1NGA; TASURGRATINIB [INN]; E-7090
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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 : ~100 mg/mL (~170.2 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.25 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 (4.25 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 (4.25 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 | 1.7016 mL | 8.5082 mL | 17.0164 mL | |
| 5 mM | 0.3403 mL | 1.7016 mL | 3.4033 mL | |
| 10 mM | 0.1702 mL | 0.8508 mL | 1.7016 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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