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
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)
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
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 |
---|---|---|---|
Target ID: CHEMBL5024 |
0.2 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
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 |
T1/2
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: 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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
weak [IC50 >30 uM] | ||||
weak [IC50 >30 uM] | ||||
weak | ||||
yes [IC50 1.2995 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
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 |
|
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23222511
80 nM VX-970 (VE-822) attenuates ATR signaling in normal cells without enhancing radiation and gemcitabine killing in normal cells.
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Systematic Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Code | English |
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
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 | |||
|
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
|
PRIMARY | |||
|
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
|
PRIMARY | |||
|
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
|
PRIMARY | |||
|
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
|
PRIMARY | |||
|
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
|
PRIMARY | |||
|
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
|
PRIMARY | |||
|
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
|
PRIMARY | |||
|
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
|
PRIMARY | |||
|
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
|
PRIMARY | |||
|
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
|
PRIMARY | |||
|
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
|
PRIMARY |
ACTIVE MOIETY
SALT/SOLVATE (PARENT)