Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C32H37N5O6 |
| Molecular Weight | 587.6661 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
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=IBHOLSBDZMIPPT-UHFFFAOYSA-N
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)
| 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 |
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) |
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
| 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
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.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 18:16:33 UTC 2023
by
admin
on
Sat Dec 16 18:16:33 UTC 2023
|
| Record UNII |
TN7CUD1NGA
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Systematic Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English |
| Classification Tree | Code System | Code | ||
|---|---|---|---|---|
|
NCI_THESAURUS |
C1967
Created by
admin on Sat Dec 16 18:16:33 UTC 2023 , Edited by admin on Sat Dec 16 18:16:33 UTC 2023
|
||
|
NCI_THESAURUS |
C129825
Created by
admin on Sat Dec 16 18:16:33 UTC 2023 , Edited by admin on Sat Dec 16 18:16:33 UTC 2023
|
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
1622204-21-0
Created by
admin on Sat Dec 16 18:16:33 UTC 2023 , Edited by admin on Sat Dec 16 18:16:33 UTC 2023
|
PRIMARY | |||
|
300000022204
Created by
admin on Sat Dec 16 18:16:33 UTC 2023 , Edited by admin on Sat Dec 16 18:16:33 UTC 2023
|
PRIMARY | |||
|
C118672
Created by
admin on Sat Dec 16 18:16:33 UTC 2023 , Edited by admin on Sat Dec 16 18:16:33 UTC 2023
|
PRIMARY | |||
|
TN7CUD1NGA
Created by
admin on Sat Dec 16 18:16:33 UTC 2023 , Edited by admin on Sat Dec 16 18:16:33 UTC 2023
|
PRIMARY | |||
|
78323434
Created by
admin on Sat Dec 16 18:16:33 UTC 2023 , Edited by admin on Sat Dec 16 18:16:33 UTC 2023
|
PRIMARY | |||
|
11580
Created by
admin on Sat Dec 16 18:16:33 UTC 2023 , Edited by admin on Sat Dec 16 18:16:33 UTC 2023
|
PRIMARY | INN |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
|
SALT/SOLVATE -> PARENT |
|
||
|
TARGET -> INHIBITOR |
|
||
|
TARGET -> INHIBITOR |
|
||
|
TARGET -> INHIBITOR |
|
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
ACTIVE MOIETY |
E7090 is an orally available, selective and potent inhibitor of FGFR1, 2 and 3 tyrosine kinase activities. E7090 displayed inhibition of FGFR1, 2, and 3 kinase activities with the IC50 values of approximately 1 nmol/L. E7090 also inhibited the growth of SNU-16, human gastric cancer cell line harboring FGFR2 amplification with an IC50 value of 3 nmol/L. This activity was about 60-fold stronger than that against VEGF-stimulated HUVEC growth. Kinase profiling assay consisting of 93 kinases including non-receptor and serine/threonine kinases, also demonstrated that E7090 inhibited limited kinases including FGFR-1, -2 and -3. In addition, E7090 inhibited proliferation of human cancer cell lines harboring various types of FGFRs gene abnormalities such as amplification, mutation, or translocation in vitro, which are confirmed by the inhibition of FGFR signaling.
|
