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Details

Stereochemistry ACHIRAL
Molecular Formula C24H25N5O3S.ClH
Molecular Weight 500.013
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BERZOSERTIB HYDROCHLORIDE

SMILES

Cl.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=SUFHPZPWHPCCPI-UHFFFAOYSA-N
InChI=1S/C24H25N5O3S.ClH/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);1H

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
Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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.

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 0.2 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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

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:
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

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1587
inhibitor
1767
inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1461
UGTs
13
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2C9
1819
 weak [IC50 >30 uM]
CYP3A4
1925
 weak [IC50 >30 uM]
CYP2D6
1891
 weak
P-gp
1650
 yes [IC50 1.2995 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
UGTs
13
 no
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
PubMed

PubMed

TitleDatePubMed
Patents

Patents

20100222318
2
2010071837A1
2
WO2016112374A2
2

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 Sat Dec 16 10:52:06 UTC 2023
Edited
by admin
on Sat Dec 16 10:52:06 UTC 2023
Record UNII
9Z4ZI0QM49
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BERZOSERTIB HYDROCHLORIDE
Common Name English
VE-822 HCL
Code English
VX-970 HYDROCHLORIDE
Code English
2-PYRAZINAMINE, 3-(3-(4-((METHYLAMINO)METHYL)PHENYL)-5-ISOXAZOLYL)-5-(4-((1-METHYLETHYL)SULFONYL)PHENYL)-, HYDROCHLORIDE (1:1)
Systematic Name English
VE-822 HYDROCHLORIDE
Code English
VX-970 HCL
Code English
Code System Code Type Description
FDA UNII
9Z4ZI0QM49
Created by admin on Sat Dec 16 10:52:06 UTC 2023 , Edited by admin on Sat Dec 16 10:52:06 UTC 2023
PRIMARY
CAS
1428935-04-9
Created by admin on Sat Dec 16 10:52:06 UTC 2023 , Edited by admin on Sat Dec 16 10:52:06 UTC 2023
PRIMARY
SMS_ID
100000175104
Created by admin on Sat Dec 16 10:52:06 UTC 2023 , Edited by admin on Sat Dec 16 10:52:06 UTC 2023
PRIMARY
PUBCHEM
71537084
Created by admin on Sat Dec 16 10:52:06 UTC 2023 , Edited by admin on Sat Dec 16 10:52:06 UTC 2023
PRIMARY
Related Record Type Details
Structure of BERZOSERTIB
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of BERZOSERTIB
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