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

Structure Search

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

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26513298 | http://cancerres.aacrjournals.org/content/72/8_Supplement/4688 | http://cancerres.aacrjournals.org/content/73/8_Supplement/3323 | http://www.2xoncology.com/2x-121/

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 Target ID: CHEMBL3105 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26513298	Inhibitor 8297	2.0 nM [IC50]
Poly [ADP-ribose] polymerase 2 16 Target ID: CHEMBL5366 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26513298	Inhibitor 8297	1.0 nM [IC50]
Tankyrase-1 3 Target ID: CHEMBL6164 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26513298	Inhibitor 8297	50.0 nM [IC50]
Tankyrase-2 4 Target ID: CHEMBL6154 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26513298	Inhibitor 8297	50.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Malignant solid tumour 1 Sources: http://adisinsight.springer.com/drugs/800035250	Primary		Phase II 1132	Unknown Approved Use Unknown
B-cell malignancy, low-grade 1 Sources: http://adisinsight.springer.com/drugs/800035250	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	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	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

T_1/2

Value	Dose	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

Sourcing

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
Excenen	EX-A1282	http://www.excenen.com/searchresultlist.php?id=EX-A1282
Lab Network	LN01342490	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342490
MedChem Express	HY-12418	https://www.medchemexpress.com/search.html?q=HY-12418&ft=&fa=&fp=
MolPort	MolPort-044-727-632	https://www.molport.com/shop/molecule-link/MolPort-044-727-632
MolPort	MolPort-044-830-647	https://www.molport.com/shop/molecule-link/MolPort-044-830-647
MolPort	MolPort-046-416-891	https://www.molport.com/shop/molecule-link/MolPort-046-416-891
Molcore	MC34455	http://www.molcore.com/CatMC34455.html
Molnova	M10499	https://www.molnova.com/en/serch-list.html?keywords=M10499
MuseChem	I000532	https://www.musechem.com/product/I000532.html
Selleck Chemicals	S8419	http://www.selleckchem.com/search.html?searchDTO.searchParam=S8419
ShangHai Biochempartner	BCP19934	http://www.biochempartner.com/search_BCP19934
eMolecules	193590769	https://orderbb.emolecules.com/search/#?query=193590769
eMolecules	50283219	https://orderbb.emolecules.com/search/#?query=50283219
eMolecules	89940567	https://orderbb.emolecules.com/search/#?query=89940567
eMolecules	95706117	https://orderbb.emolecules.com/search/#?query=95706117
mcule	MCULE-3396930808	https://mcule.com/MCULE-3396930808/

PubMed

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

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 Created by `admin` on `Sat Dec 16 01:01:29 UTC 2023` Edited by `admin` on `Sat Dec 16 01:01:29 UTC 2023`
Record UNII	9X5A2QIA7C
Record Status	`Validated (UNII)`
Record Version

Download

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