berzosertib   Click here for help

GtoPdb Ligand ID: 8003

Synonyms: M6620 | VE 822 | VE-822 | VX-970 | VX970
Compound class: Synthetic organic
Comment: Berzosertib (VE-822) is a potent and selective inhibitor of the serine/threonine kinase ATR [7]. The structure of VE-822 is claimed in patent US20130089626 [6]. VE-822 is under investigated for its potential antineoplastic action [1,3].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

berzosertib is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 132.38
Molecular weight 463.17
XLogP 3.77
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CNCc1ccc(cc1)c1noc(c1)c1nc(cnc1N)c1ccc(cc1)S(=O)(=O)C(C)C
Isomeric SMILES CNCc1ccc(cc1)c1noc(c1)c1nc(cnc1N)c1ccc(cc1)S(=O)(=O)C(C)C
InChI 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)
InChI Key JZCWLJDSIRUGIN-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Charrier JD, Durrant SJ, Golec JM, Kay DP, Knegtel RM, MacCormick S, Mortimore M, O'Donnell ME, Pinder JL, Reaper PM et al.. (2011)
Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents.
J Med Chem, 54 (7): 2320-30. [PMID:21413798]
2. Fokas E, Prevo R, Pollard JR, Reaper PM, Charlton PA, Cornelissen B, Vallis KA, Hammond EM, Olcina MM, Gillies McKenna W et al.. (2012)
Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation.
Cell Death Dis, 3: e441. [PMID:23222511]
3. Gorecki L, Andrs M, Rezacova M, Korabecny J. (2020)
Discovery of ATR kinase inhibitor berzosertib (VX-970, M6620): Clinical candidate for cancer therapy.
Pharmacol Ther, 210: 107518. [PMID:32109490]
4. Konstantinopoulos PA, Cheng SC, Wahner Hendrickson AE, Penson RT, Schumer ST, Doyle LA, Lee EK, Kohn EC, Duska LR, Crispens MA et al.. (2020)
Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial.
Lancet Oncol, 21 (7): 957-968. [PMID:32553118]
5. Minchom A, Aversa C, Lopez J. (2018)
Dancing with the DNA damage response: next-generation anti-cancer therapeutic strategies.
Ther Adv Med Oncol, 10: 1758835918786658. [PMID:30023007]
6. Pollard JR, Reaper PM. (2013)
Treating Cancer with ATR Inhibitors.
Patent number: US20130089626. Assignee: Vertex Pharmaceuticals Incorporated. Priority date: 30/09/2011. Publication date: 11/04/2013.
7. Shi Q, Shen LY, Dong B, Fu H, Kang XZ, Yang YB, Dai L, Yan WP, Xiong HC, Liang Z et al.. (2018)
The identification of the ATR inhibitor VE-822 as a therapeutic strategy for enhancing cisplatin chemosensitivity in esophageal squamous cell carcinoma.
Cancer Lett, 432: 56-68. [PMID:29890208]