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Details

Stereochemistry ACHIRAL
Molecular Formula C32H37N5O6.C4H6O4
Molecular Weight 705.7541
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TASURGRATINIB SUCCINATE

SMILES

OC(=O)CCC(O)=O.CNC(=O)N1C=CC2=CC(OC3=CC=NC(NC(=O)C4=CC=C(C=C4)C5CCN(CCO)CC5)=C3)=C(OCCOC)C=C12

InChI

InChIKey=DLFIYSXIMACKCX-UHFFFAOYSA-N
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)

HIDE SMILES / InChI
E-7090 is a novel selective inhibitor of fibroblast growth factor receptors, that displays potent anti-tumor activity. It is a promising candidate as a therapeutic agent for the treatment of tumors harboring FGFR genetic abnormalities. E-7090 is an orally available and selective inhibitor of the tyrosine kinase activities of FGFR1, -2, and -3. In kinetic analyses E-7090 associated more rapidly with FGFR1 than did the type II FGFR1 inhibitor ponatinib, and E-7090 dissociated more slowly from FGFR1, with a relatively longer residence time, than did the type I FGFR1 inhibitor AZD4547, suggesting that its kinetics are more similar to the type V inhibitors, such as lenvatinib. E-7090 showed selective antiproliferative activity against cancer cell lines harboring FGFR genetic abnormalities and decreased tumor size in a mouse xenograft model using cell lines with dysregulated FGFR. Furthermore, E-7090 administration significantly prolonged the survival of mice with metastasized tumors in the lung. It is being investigated in a Phase I clinical trial for treatment of patients with solid tumors.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P11362|||Q14307|||Q9UDF2
Gene ID: 2260.0
Gene Symbol: FGFR1
Target Organism: Homo sapiens (Human)
0.7 nM [IC50]
Target ID: P21802|||Q14301|||Q1KHY5|||Q9NZU3|||Q9UIH8
Gene ID: 2263.0
Gene Symbol: FGFR2
Target Organism: Homo sapiens (Human)
0.5 nM [IC50]
Target ID: P22607
Gene ID: 2261.0
Gene Symbol: FGFR3
Target Organism: Homo sapiens (Human)
1.2 nM [IC50]
Conditions
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
337 ng/mL
180 mg 1 times / day multiple, oral
dose: 180 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
E-7090 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
372 ng/mL
140 mg 1 times / day multiple, oral
dose: 140 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
E-7090 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
154 ng/mL
180 mg single, oral
dose: 180 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
E-7090 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
227 ng/mL
140 mg single, oral
dose: 140 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
E-7090 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3860 ng × h/mL
180 mg 1 times / day multiple, oral
dose: 180 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
E-7090 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4700 ng × h/mL
140 mg 1 times / day multiple, oral
dose: 140 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
E-7090 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2610 ng × h/mL
180 mg single, oral
dose: 180 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
E-7090 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4050 ng × h/mL
140 mg single, oral
dose: 140 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
E-7090 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
24 h
180 mg single, oral
dose: 180 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
E-7090 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
27 h
140 mg single, oral
dose: 140 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
E-7090 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
180 mg 1 times / day multiple, oral
Highest studied dose
Dose: 180 mg, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg, 1 times / day
Sources: Page: p.574
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.574
DLT: ALT increased, AST increased...
Dose limiting toxicities:
ALT increased (grade 3, 33.3%)
AST increased (grade 3, 33.3%)
Sources: Page: p.574
AEs

AEs

AESignificanceDosePopulation
ALT increased grade 3, 33.3%
DLT
180 mg 1 times / day multiple, oral
Highest studied dose
Dose: 180 mg, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg, 1 times / day
Sources: Page: p.574
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.574
AST increased grade 3, 33.3%
DLT
180 mg 1 times / day multiple, oral
Highest studied dose
Dose: 180 mg, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg, 1 times / day
Sources: Page: p.574
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.574
PubMed

PubMed

TitleDatePubMed
E7090, a Novel Selective Inhibitor of Fibroblast Growth Factor Receptors, Displays Potent Antitumor Activity and Prolongs Survival in Preclinical Models.
2016 Nov
Patents

Patents

Sample Use Guides

E-7090 starting dose 1 mg once a day with dose escalation in Cycle 1 in patients with solid tumors. Cycle 0 is for 7 days. For Cycle 1 and onward, each cycle is 28 days long. Subjects can continue treatment unless they meet discontinuation criteria.
Route of Administration: Oral
E-7090 was tested on a panel of 39 human cancer cell lines in cell proliferation assays. The IC50 values observed ranged from 2 nM to greater than 10,000 nM. Thirteen cell lines were highly sensitive to E-7090, with IC50 values less than 100 nM. SNU-16 (human gastric cancer cell line) cells were treated with the indicated concentrations of E-7090 succinate in RPMI1640 containing 10% FBS for 4 hours and lysed with RIPA buffer containing protease and phosphatase inhibitors. E7090 succinate inhibited SNU-16 cell proliferation with an IC50 value of 5.7 nM.
Name Type Language
TASURGRATINIB SUCCINATE
Common Name English
BUTANEDIOIC ACID, COMPD. WITH 5-((2-((4-(1-(2-HYDROXYETHYL)-4-PIPERIDINYL)BENZOYL)AMINO)-4-PYRIDINYL)OXY)-6-(2-METHOXYETHOXY)-N-METHYL-1H-INDOLE-1-CARBOXAMIDE (3:2)
Systematic Name English
5-((2-(((4-(1-(2-HYDROXYETHYL)PIPERIDIN-4-YL)PHENYL)CARBONYL)AMINO)PYRIDIN-4-YL)OXY)-6-(2-METHOXYETHOXY)-N-METHYL-1H-INDOLE-1-CARBOXAMIDESUCCINATE (1:1.5)
Systematic Name English
Code System Code Type Description
CAS
1879965-80-6
Created by admin on Sat Dec 16 18:23:01 GMT 2023 , Edited by admin on Sat Dec 16 18:23:01 GMT 2023
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SMS_ID
300000022205
Created by admin on Sat Dec 16 18:23:01 GMT 2023 , Edited by admin on Sat Dec 16 18:23:01 GMT 2023
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PUBCHEM
129275025
Created by admin on Sat Dec 16 18:23:01 GMT 2023 , Edited by admin on Sat Dec 16 18:23:01 GMT 2023
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FDA UNII
YRZ52NF9Y4
Created by admin on Sat Dec 16 18:23:01 GMT 2023 , Edited by admin on Sat Dec 16 18:23:01 GMT 2023
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