BERZOSERTIB

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=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
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 8297		0.2 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Fallopian tube cancer 17 Sources: http://adisinsight.springer.com/drugs/800037997	Primary	Phase II 1132	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: http://adisinsight.springer.com/drugs/800037997	Primary	Phase II 1132	Unknown Approved Use Unknown
Peritoneal carcinoma 2 Sources: http://adisinsight.springer.com/drugs/800037997	Primary	Phase II 1132	Unknown Approved Use Unknown
Small-cell lung cancer 41 Sources: http://adisinsight.springer.com/drugs/800037997	Primary	Phase II 1132	Unknown Approved Use Unknown
Urothelial cancer 4 Sources: http://adisinsight.springer.com/drugs/800037997	Primary	Phase II 1132	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 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: https://pubmed.ncbi.nlm.nih.gov/32568634 Page: p.3197	Sources: https://pubmed.ncbi.nlm.nih.gov/32568634 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: https://pubmed.ncbi.nlm.nih.gov/32568634 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: https://pubmed.ncbi.nlm.nih.gov/32568634 Page: p.3197	Sources: https://pubmed.ncbi.nlm.nih.gov/32568634 Page: p.3197

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461	UGTs 13

Drug as perpetrator

Target	Modality	Activity
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/31074988/ \| https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363680204	weak [IC50 >30 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/31074988/	weak [IC50 >30 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/31074988/	weak
P-gp 1650	inhibitor 3277 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 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28888173/	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/31074988/

PubMed

Title	Date	PubMed
Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents.	2011 Apr 14	21413798
Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation.	2012 Dec 6	23222511
Potentiation of tumor responses to DNA damaging therapy by the selective ATR inhibitor VX-970.	2014 Jul 30	25010037
Drugging ATR: progress in the development of specific inhibitors for the treatment of cancer.	2015	26061106
Preclinical testing of an Atr inhibitor demonstrates improved response to standard therapies for esophageal cancer.	2016 Nov	27839769

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.

Name

Type

Language

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

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 UTC 2023 , Edited by admin on Sat Dec 16 10:52:07 UTC 2023

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DRUG BANK

DB11794

Created by admin on Sat Dec 16 10:52:07 UTC 2023 , Edited by admin on Sat Dec 16 10:52:07 UTC 2023

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NCI_THESAURUS

C116355

Created by admin on Sat Dec 16 10:52:07 UTC 2023 , Edited by admin on Sat Dec 16 10:52:07 UTC 2023

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EPA CompTox

DTXSID601025940

Created by admin on Sat Dec 16 10:52:07 UTC 2023 , Edited by admin on Sat Dec 16 10:52:07 UTC 2023

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CAS

1232416-25-9

Created by admin on Sat Dec 16 10:52:06 UTC 2023 , Edited by admin on Sat Dec 16 10:52:06 UTC 2023

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SMS_ID

100000175098

Created by admin on Sat Dec 16 10:52:07 UTC 2023 , Edited by admin on Sat Dec 16 10:52:07 UTC 2023

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WIKIPEDIA

Berzosertib

Created by admin on Sat Dec 16 10:52:07 UTC 2023 , Edited by admin on Sat Dec 16 10:52:07 UTC 2023

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FDA UNII

L423PRV3V3

Created by admin on Sat Dec 16 10:52:07 UTC 2023 , Edited by admin on Sat Dec 16 10:52:07 UTC 2023

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INN

10538

Created by admin on Sat Dec 16 10:52:07 UTC 2023 , Edited by admin on Sat Dec 16 10:52:07 UTC 2023

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INCB IDS CODE

10538

Created by admin on Sat Dec 16 10:52:07 UTC 2023 , Edited by admin on Sat Dec 16 10:52:07 UTC 2023

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USAN

DE-73

Created by admin on Sat Dec 16 10:52:07 UTC 2023 , Edited by admin on Sat Dec 16 10:52:07 UTC 2023

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PUBCHEM

59472121

Created by admin on Sat Dec 16 10:52:07 UTC 2023 , Edited by admin on Sat Dec 16 10:52:07 UTC 2023

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ACTIVE MOIETY


					L423PRV3V3

BERZOSERTIB

SALT/SOLVATE (PARENT)


					9Z4ZI0QM49

BERZOSERTIB HYDROCHLORIDE

Details

SMILES

InChI

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

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Approved Use

Approved Use

Approved Use

Cmax

AUC

T1/2

Doses

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Patents

Sample Use Guides

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

C_max

T_1/2

Drug as perpetrator