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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
Structure of 2X-121

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)

HIDE SMILES / InChI
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.0 nM [IC50]
1.0 nM [IC50]
50.0 nM [IC50]
50.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
4430 ng/mL
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
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
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
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
11300 ng × h/mL
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
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
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
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
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
9.45 h
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
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
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
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
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
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
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
E7449: A dual inhibitor of PARP1/2 and tankyrase1/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling.
2015 Dec 1
Patents

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
10 uM E7449 inhibits Wnt signaling in vitro (effects of E7449 treatment on Wnt proteins in SW480 cells)
Name Type Language
2X-121
Code English
Stenoparib [WHO-DD]
Common Name English
3H-PYRIDAZINO(3,4,5-DE)QUINAZOLIN-3-ONE, 8-((1,3-DIHYDRO-2H-ISOINDOL-2-YL)METHYL)-1,2-DIHYDRO-
Systematic Name English
E-7449
Code English
PARP INHIBITOR 2X-121
Common Name English
E7449
Code English
Code System Code Type Description
SMS_ID
300000021731
Created by admin on Sat Dec 16 01:01:29 GMT 2023 , Edited by admin on Sat Dec 16 01:01:29 GMT 2023
PRIMARY
NCI_THESAURUS
C102746
Created by admin on Sat Dec 16 01:01:29 GMT 2023 , Edited by admin on Sat Dec 16 01:01:29 GMT 2023
PRIMARY
FDA UNII
9X5A2QIA7C
Created by admin on Sat Dec 16 01:01:29 GMT 2023 , Edited by admin on Sat Dec 16 01:01:29 GMT 2023
PRIMARY
PUBCHEM
135565981
Created by admin on Sat Dec 16 01:01:29 GMT 2023 , Edited by admin on Sat Dec 16 01:01:29 GMT 2023
PRIMARY
CAS
1140964-99-3
Created by admin on Sat Dec 16 01:01:29 GMT 2023 , Edited by admin on Sat Dec 16 01:01:29 GMT 2023
PRIMARY