XRD-0394   Click here for help

GtoPdb Ligand ID: 13457

Synonyms: compound 569 [WO2021022078A1] | XRD 0394 | XRD0394
Compound class: Synthetic organic
Comment: XRD-0394 is a dual inhibitor of the DNA damage response kinases ATM and DNA-PK [2]. It is proposed as a radiosensitising adjunct for cancer radiotherapy. XRD-0394 also potentiates the in vitro efficacy of topoisomerase I inhibitors and PARP inhibitors. The chemical structure for XRD-0394 is one of the compounds (569) claimed in WO2021022078A1 [1].
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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

XRD-0394 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 9
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 120.84
Molecular weight 527.61
XLogP 1.13
No. Lipinski's rules broken 1

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 CC(C)NCCOC1=NC=C(C=C1NS(=O)(=O)C)C2=C(C=C3C(=C2)C4=C(C=N3)N(C)C(=O)C54CCC5)F
Isomeric SMILES CC(C)NCCOC1=NC=C(C=C1NS(C)(=O)=O)C2=CC3=C(C=C2F)N=CC4=C3C5(CCC5)C(=O)N4C
InChI InChI=1S/C26H30FN5O4S/c1-15(2)28-8-9-36-24-21(31-37(4,34)35)10-16(13-30-24)17-11-18-20(12-19(17)27)29-14-22-23(18)26(6-5-7-26)25(33)32(22)3/h10-15,28,31H,5-9H2,1-4H3
InChI Key DFPIFDHNNWOIDD-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. Fu J, Wang Y, Sun Y, Wu G, Lu A, Zhang S, Goodnow RA, Gilmer T, Kastan M, Kirsch D. (2021)
Dual atm and dna-pk inhibitors for use in anti-tumor therapy.
Patent number: WO2021022078A1. Assignee: Xrad Therapeutics, Inc.. Priority date: 30/07/2020. Publication date: 04/02/2021.
2. Gilmer TM, Lai CH, Guo K, Deland K, Ashcraft KA, Stewart AE, Wang Y, Fu J, Wood KC, Kirsch DG et al.. (2024)
A Novel Dual ATM/DNA-PK Inhibitor, XRD-0394, Potently Radiosensitizes and Potentiates PARP and Topoisomerase I Inhibitors.
Mol Cancer Ther, 23 (6): 751-765. [PMID:38588408]