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
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)
Molecular Formula | C4H6O4 |
Molecular Weight | 118.088 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | C32H37N5O6 |
Molecular Weight | 587.6661 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/27535969
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27535969
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P11362|||Q14307|||Q9UDF2 Gene ID: 2260.0 Gene Symbol: FGFR1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/27535969 |
0.7 nM [IC50] | ||
Target ID: P21802|||Q14301|||Q1KHY5|||Q9NZU3|||Q9UIH8 Gene ID: 2263.0 Gene Symbol: FGFR2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/27535969 |
0.5 nM [IC50] | ||
Target ID: P22607 Gene ID: 2261.0 Gene Symbol: FGFR3 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/27535969 |
1.2 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
337 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31797489 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31797489 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31797489 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31797489 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3860 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31797489 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31797489 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31797489 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31797489 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
24 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31797489 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31797489 |
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
Dose | Population | Adverse 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%) Sources: Page: p.574AST increased (grade 3, 33.3%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27535969
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27535969
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.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 18:23:01 GMT 2023
by
admin
on
Sat Dec 16 18:23:01 GMT 2023
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Record UNII |
YRZ52NF9Y4
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Record Status |
Validated (UNII)
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Record Version |
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YRZ52NF9Y4
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