2X-121

Investigational

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)

HIDE SMILES / InChI

Molecular Formula	C18H15N5O
Molecular Weight	317.3446
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Poly [ADP-ribose] polymerase-1 23	Inhibitor 8,504	2.0 nM [IC50]
Poly [ADP-ribose] polymerase 2 16	Inhibitor 8,504	1.0 nM [IC50]
Tankyrase-1 3	Inhibitor 8,504	50.0 nM [IC50]
Tankyrase-2 4	Inhibitor 8,504	50.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Malignant solid tumour 1	Primary		Phase II 1,147	Unknown
B-cell malignancy, low-grade 1	Primary		Phase II 1,147	Unknown

C_max

Value	Dose	Analyte	Population
2230 ng/mL	600 mg 1 times / day steady-state, oral	E-7449 plasma	Homo sapiens
4430 ng/mL	800 mg single, oral	E-7449 plasma	Homo sapiens
1130 ng/mL	400 mg 1 times / day steady-state, oral	E-7449 plasma	Homo sapiens
2250 ng/mL	600 mg single, oral	E-7449 plasma	Homo sapiens
999 ng/mL	400 mg single, oral	E-7449 plasma	Homo sapiens
4120 ng/mL	800 mg 1 times / day steady-state, oral	E-7449 plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
9660 ng × h/mL	600 mg 1 times / day steady-state, oral	E-7449 plasma	Homo sapiens
11300 ng × h/mL	800 mg single, oral	E-7449 plasma	Homo sapiens
3240 ng × h/mL	400 mg 1 times / day steady-state, oral	E-7449 plasma	Homo sapiens
7930 ng × h/mL	600 mg single, oral	E-7449 plasma	Homo sapiens
4690 ng × h/mL	400 mg single, oral	E-7449 plasma	Homo sapiens
12000 ng × h/mL	800 mg 1 times / day steady-state, oral	E-7449 plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
5.05 h	600 mg 1 times / day steady-state, oral	E-7449 plasma	Homo sapiens
9.45 h	800 mg single, oral	E-7449 plasma	Homo sapiens
4.16 h	400 mg 1 times / day steady-state, oral	E-7449 plasma	Homo sapiens
7.17 h	600 mg single, oral	E-7449 plasma	Homo sapiens
8.62 h	400 mg single, oral	E-7449 plasma	Homo sapiens
6.44 h	800 mg 1 times / day steady-state, oral	E-7449 plasma	Homo sapiens

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
001 Chemical	DY34455	https://www.001chemical.com/chem/search?q=DY34455
1PlusChem LLC	1P000B0R	https://www.1pchem.com/search?query=1P000B0R
BLD Pharm	BD629929	http://www.bldpharm.com/search/Search.html?keyword=BD629929
Cayman Chemical	21658	http://www.caymanchem.com/app/template/Product.vm/catalog/21658
Chem Scene	CS-3479	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3479

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PubMed

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Title	Date	PubMed
E7449: A dual inhibitor of PARP1/2 and tankyrase1/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling.	2015 Dec 1	26513298

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Patents

Sample Use Guides

In Vivo Use Guide

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

10 uM E7449 inhibits Wnt signaling in vitro (effects of E7449 treatment on Wnt proteins in SW480 cells)

Substance Class	Chemical
Record UNII	9X5A2QIA7C
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

E7449

Preferred Name

English

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

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Code System

Code

Type

Description

SMS_ID

300000021731

PRIMARY

NCI_THESAURUS

C102746

PRIMARY

FDA UNII

9X5A2QIA7C

PRIMARY

PUBCHEM

135565981

PRIMARY

CAS

1140964-99-3

PRIMARY

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Related Record

Type

Details


					U25G2OFC53

POLY (ADP-RIBOSE) POLYMERASE 1

TARGET -> INHIBITOR

Interaction Type:

INHIBITOR

Qualification:

IC50

Amount:

RELATIONSHIP_AMOUNT 1 NANOMOLAR (average)


					H08O6RQ8BJ

POLY (ADP-RIBOSE) POLYMERASE TANKYRASE-1

TARGET -> INHIBITOR

Comments:

RADIOACTIVE NAD ASSAY

Qualification:

IC50

Amount:

50 NANOMOLAR (average)


					MGS9V9P88C

POLY (ADP-RIBOSE) POLYMERASE TANKYRASE-2

TARGET -> INHIBITOR

Comments:

RADIOACTIVE NAD ASSAY

Qualification:

IC50

Amount:

50 NANOMOLAR (average)


					LZ0P651QHS

POLY (ADP-RIBOSE) POLYMERASE 2

TARGET -> INHIBITOR

Interaction Type:

INHIBITOR

Qualification:

IC50

Amount:

RELATIONSHIP_AMOUNT 1.2 NANOMOLAR (average)

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Related Record

Type

Details


					9X5A2QIA7C

2X-121

ACTIVE MOIETY

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SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2