BERZOSERTIB

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H25N5O3S
Molecular Weight	463.552
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNCC1=CC=C(C=C1)C2=NOC(=C2)C3=C(N)N=CC(=N3)C4=CC=C(C=C4)S(=O)(=O)C(C)C

InChI

InChIKey=JZCWLJDSIRUGIN-UHFFFAOYSA-N

InChI=1S/C24H25N5O3S/c1-15(2)33(30,31)19-10-8-18(9-11-19)21-14-27-24(25)23(28-21)22-12-20(29-32-22)17-6-4-16(5-7-17)13-26-3/h4-12,14-15,26H,13H2,1-3H3,(H2,25,27)

HIDE SMILES / InChI

Molecular Formula	C24H25N5O3S
Molecular Weight	463.552
Charge	0
Count

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

Description
Sources: http://adisinsight.springer.com/drugs/800037997
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23222511

VX-970 (VE-822) is an ATR kinase inhibitor. VE-822 decreased maintenance of cell-cycle checkpoints, increased persistent DNA damage and decreased homologous recombination in irradiated cancer cells. Vertex Pharmaceuticals is developing VX 970 for the treatment of advanced solid tumours. Phase I/II development is underway in the US for small-cell lung cancer and in the UK for solid tumours. Phase II development of VX 970 as a combination therapy in urogenital cancer, ovarian, primary peritoneal and fallopian tube cancer indications is underway in the US.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine-protein kinase ATR 5 Target ID: CHEMBL5024 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23222511 \| https://www.ncbi.nlm.nih.gov/pubmed/21413798	Inhibitor 8504		0.2 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Fallopian tube cancer 17 Sources: http://adisinsight.springer.com/drugs/800037997	Primary	Phase II 1147	Unknown Approved Use Unknown
Ovarian cancer 160 Sources: http://adisinsight.springer.com/drugs/800037997	Primary	Phase II 1147	Unknown Approved Use Unknown
Peritoneal carcinoma 2 Sources: http://adisinsight.springer.com/drugs/800037997	Primary	Phase II 1147	Unknown Approved Use Unknown
Small-cell lung cancer 41 Sources: http://adisinsight.springer.com/drugs/800037997	Primary	Phase II 1147	Unknown Approved Use Unknown
Urothelial cancer 4 Sources: http://adisinsight.springer.com/drugs/800037997	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
4410 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32568634	480 mg/m² single, intravenous dose: 480 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		VX-970 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1520 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32568634	240 mg/m² 1 times / week single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		VX-970 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
14900 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32568634	480 mg/m² single, intravenous dose: 480 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		VX-970 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8270 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32568634	240 mg/m² 1 times / week single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		VX-970 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
21.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32568634	480 mg/m² single, intravenous dose: 480 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		VX-970 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
17.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32568634	240 mg/m² 1 times / week single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		VX-970 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
240 mg/m2 2 times / week multiple, intravenous RP2D Dose: 240 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 240 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32568634	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/32568634	Sources: https://pubmed.ncbi.nlm.nih.gov/32568634
480 mg/m2 1 times / week multiple, intravenous Studied dose Dose: 480 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 480 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/32568634	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/32568634	Sources: https://pubmed.ncbi.nlm.nih.gov/32568634

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741	UGTs 13

Drug as perpetrator

Target	Modality	Activity
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/31074988/ \| https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363680204	weak [IC50 >30 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/31074988/	weak [IC50 >30 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/31074988/	weak
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363680204	yes [IC50 1.2995 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
UGTs 13	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/28888173/	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/31074988/

PubMed

Title	Date	PubMed
Preclinical testing of an Atr inhibitor demonstrates improved response to standard therapies for esophageal cancer.	2016-11	27839769
Drugging ATR: progress in the development of specific inhibitors for the treatment of cancer.	2015	26061106
ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses.	2014-12-01	25269479
Potentiation of tumor responses to DNA damaging therapy by the selective ATR inhibitor VX-970.	2014-07-30	25010037
Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation.	2012-12-06	23222511
Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents.	2011-04-14	21413798

Patents

Sample Use Guides

In Vivo Use Guide

Intravenous VX-970 (VE-822) is in clinical trials for the treatment of cancer, however dosage is not known. VX-970 (VE-822) (30-60 mg/kg) was administered by oral gavage in mouse cancer xenograft models.

Route of Administration: Other

In Vitro Use Guide

80 nM VX-970 (VE-822) attenuates ATR signaling in normal cells without enhancing radiation and gemcitabine killing in normal cells.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 23:29:06 GMT 2025` Edited by `admin` on `Mon Mar 31 23:29:06 GMT 2025`
Record UNII	L423PRV3V3
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VE-822

Preferred Name

English

BERZOSERTIB

Official Name

English

3-(3-{4-[(Methylamino)methyl]phenyl}-1,2-oxazol-5-yl)-5-[4-(propane-2-sulfonyl)phenyl]pyrazin-2-amine

Systematic Name

English

Berzosertib [WHO-DD]

Common Name

English

M6620

Code

English

2-PYRAZINAMINE, 3-(3-(4-((METHYLAMINO)METHYL)PHENYL)-5-ISOXAZOLYL)-5-(4-((1-METHYLETHYL)SULFONYL)PHENYL)-

Systematic Name

English

VX970

Code

English

BERZOSERTIB [USAN]

Common Name

English

M-6620

Code

English

berzosertib [INN]

Common Name

English

VX-970

Code

English

Code System Code Type Description

ChEMBL

CHEMBL3545202