Tasurgratinib (E-7090) succinate is a novel and potent FGFR1/2/3/4 (fibroblast growth factor receptor) inhibitor with anticancer activity. Inhibits FGFR1, -2, and -3 with IC50 of 0.71, 0.50 and 1.2 nM.

Physicochemical Properties

Molecular Formula	C36H43N5O10
Molecular Weight	705.754129648209
Exact Mass	705.3
CAS #	1879965-80-6
Related CAS #	E7090;1622204-21-0
PubChem CID	129275025
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	12
Rotatable Bond Count	14
Heavy Atom Count	51
Complexity	973
Defined Atom Stereocenter Count	0
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
InChi Key	DLFIYSXIMACKCX-UHFFFAOYSA-N
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)
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
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 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)

Biological Activity

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].
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.
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.
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.
References	[1]. E7090: A potent and selective FGFR inhibitor with activity in multiple FGFR-driven cancer models with distinct mechanisms of activation. AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. [2]. E7090, a Novel Selective Inhibitor of Fibroblast Growth Factor Receptors, Displays Potent Antitumor Activity and Prolongs Survival in Preclinical Models. Mol Cancer Ther. 2016 Nov;15(11):2630-2639.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~130.75 mM)

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. 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. 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 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	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.