Details
Stereochemistry | ACHIRAL |
Molecular Formula | C18H15N5O |
Molecular Weight | 317.3446 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O=C1NN=C2NC(CN3CC4=C(C3)C=CC=C4)=NC5=C2C1=CC=C5
InChI
InChIKey=JLFSBHQQXIAQEC-UHFFFAOYSA-N
InChI=1S/C18H15N5O/c24-18-13-6-3-7-14-16(13)17(21-22-18)20-15(19-14)10-23-8-11-4-1-2-5-12(11)9-23/h1-7H,8-10H2,(H,22,24)(H,19,20,21)
E7449 also known as 2X-121 (8-(isoindolin-2-ylmethyl)-2,9-dihydro-
3H-pyridazino[3,4,5-de]quinazolin-3-one) is an orally
bioavailable, brain penetrable, small molecule dual Poly(ADP-ribose) polymerase /Tankyrase
inhibitor that is not a substrate for P-glycoprotein. It demonstrates potent antineoplastic potential both in vivo and in vitro. 2X Oncology is developing E7449 for the treatment of solid cancers.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3105 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26513298 |
2.0 nM [IC50] | ||
Target ID: CHEMBL5366 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26513298 |
1.0 nM [IC50] | ||
Target ID: CHEMBL6164 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26513298 |
50.0 nM [IC50] | ||
Target ID: CHEMBL6154 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26513298 |
50.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4430 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
999 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2250 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
4120 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1130 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2230 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
11300 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
4690 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
7930 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
12000 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3240 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
9660 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
9.45 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
8.62 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
7.17 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
6.44 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
4.16 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
5.05 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32523090 |
600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
E-7449 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Sample Use Guides
In an in vivo subcutaneous MDA-MB-436 xenograft model, administration of E7449 at 30 or 100 mg/kg once daily for 28 days resulted in statistically significant antitumor activity.
Oral E7449 was studied in the Phase 1/2 trial in subjects with advanced solid tumors or with B-cell malignancies however dosage was not disclosed.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26513298
10 uM E7449 inhibits Wnt signaling in vitro (effects of E7449 treatment on Wnt proteins in SW480 cells)
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300000021731
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C102746
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9X5A2QIA7C
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135565981
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1140964-99-3
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ACTIVE MOIETY