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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 of BERZOSERTIB

SMILES

CNCC1=CC=C(C=C1)C2=NOC(=C2)C3=NC(=CN=C3N)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

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.2 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
4410 ng/mL
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
14900 ng × h/mL
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
21.2 h
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
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

Doses

DosePopulationAdverse 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: Page: p.3197
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.3197
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: Page: p.3197
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.3197
Overview

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents.
2011 Apr 14
Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation.
2012 Dec 6
ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses.
2014 Dec 1
Potentiation of tumor responses to DNA damaging therapy by the selective ATR inhibitor VX-970.
2014 Jul 30
Drugging ATR: progress in the development of specific inhibitors for the treatment of cancer.
2015
Preclinical testing of an Atr inhibitor demonstrates improved response to standard therapies for esophageal cancer.
2016 Nov
Patents

Sample Use Guides

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
80 nM VX-970 (VE-822) attenuates ATR signaling in normal cells without enhancing radiation and gemcitabine killing in normal cells.
Name Type Language
BERZOSERTIB
USAN   INN  
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
VE-822
Code English
VX-970
Code English
Code System Code Type Description
ChEMBL
CHEMBL3545202
Created by admin on Sat Dec 16 10:52:07 GMT 2023 , Edited by admin on Sat Dec 16 10:52:07 GMT 2023
PRIMARY
DRUG BANK
DB11794
Created by admin on Sat Dec 16 10:52:07 GMT 2023 , Edited by admin on Sat Dec 16 10:52:07 GMT 2023
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NCI_THESAURUS
C116355
Created by admin on Sat Dec 16 10:52:07 GMT 2023 , Edited by admin on Sat Dec 16 10:52:07 GMT 2023
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EPA CompTox
DTXSID601025940
Created by admin on Sat Dec 16 10:52:07 GMT 2023 , Edited by admin on Sat Dec 16 10:52:07 GMT 2023
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CAS
1232416-25-9
Created by admin on Sat Dec 16 10:52:06 GMT 2023 , Edited by admin on Sat Dec 16 10:52:06 GMT 2023
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SMS_ID
100000175098
Created by admin on Sat Dec 16 10:52:07 GMT 2023 , Edited by admin on Sat Dec 16 10:52:07 GMT 2023
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WIKIPEDIA
Berzosertib
Created by admin on Sat Dec 16 10:52:07 GMT 2023 , Edited by admin on Sat Dec 16 10:52:07 GMT 2023
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FDA UNII
L423PRV3V3
Created by admin on Sat Dec 16 10:52:07 GMT 2023 , Edited by admin on Sat Dec 16 10:52:07 GMT 2023
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INN
10538
Created by admin on Sat Dec 16 10:52:07 GMT 2023 , Edited by admin on Sat Dec 16 10:52:07 GMT 2023
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INCB IDS CODE
10538
Created by admin on Sat Dec 16 10:52:07 GMT 2023 , Edited by admin on Sat Dec 16 10:52:07 GMT 2023
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USAN
DE-73
Created by admin on Sat Dec 16 10:52:07 GMT 2023 , Edited by admin on Sat Dec 16 10:52:07 GMT 2023
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PUBCHEM
59472121
Created by admin on Sat Dec 16 10:52:07 GMT 2023 , Edited by admin on Sat Dec 16 10:52:07 GMT 2023
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