NU-7441   Click here for help

GtoPdb Ligand ID: 8010

Synonyms: KU-57788 | NU7441
PDB Ligand
Compound class: Synthetic organic
Comment: NU-7441 is a potent and selective, ATP-competitive inhibitor of DNA-dependent protein kinase (DNA-PK) [2]. It is compound 22g in Leahy et al. (2004) [2].
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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

NU-7441 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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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 3
Hydrogen bond donors 0
Rotatable bonds 2
Topological polar surface area 70.92
Molecular weight 413.11
XLogP 7.08
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 O=c1cc(oc2c1cccc2c1cccc2c1sc1c2cccc1)N1CCOCC1
Isomeric SMILES O=c1cc(oc2c1cccc2c1cccc2c1sc1c2cccc1)N1CCOCC1
InChI InChI=1S/C25H19NO3S/c27-21-15-23(26-11-13-28-14-12-26)29-24-17(6-3-9-20(21)24)19-8-4-7-18-16-5-1-2-10-22(16)30-25(18)19/h1-10,15H,11-14H2
InChI Key JAMULYFATHSZJM-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. Kodama M, Murakami M, Kodama T. (1997)
Differential implications of the oncogene-tumor suppressor gene complex in the geneses of 19 human neoplasias. Evidence in support of the steroid carcinogenesis hypothesis.
Anticancer Res, 17 (3C): 2285-92. [PMID:9216703]
2. Leahy JJ, Golding BT, Griffin RJ, Hardcastle IR, Richardson C, Rigoreau L, Smith GC. (2004)
Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries.
Bioorg Med Chem Lett, 14 (24): 6083-7. [PMID:15546735]
3. Rosenzweig KE, Youmell MB, Palayoor ST, Price BD. (1997)
Radiosensitization of human tumor cells by the phosphatidylinositol3-kinase inhibitors wortmannin and LY294002 correlates with inhibition of DNA-dependent protein kinase and prolonged G2-M delay.
Clin Cancer Res, 3 (7): 1149-56. [PMID:9815794]
4. Smith GC, Jackson SP. (1999)
The DNA-dependent protein kinase.
Genes Dev, 13 (8): 916-34. [PMID:10215620]
5. Smith GCM, Jackson SP. (2003)
Chapter 93 – The PIKK Family of Protein Kinases.  In  Handbook of Cell Signaling Volume 1
Edited by Dennis EA (Academic Press, Elsevier Inc) 557-561. [ISBN:9780121245467]
6. Zhao Y, Thomas HD, Batey MA, Cowell IG, Richardson CJ, Griffin RJ, Calvert AH, Newell DR, Smith GC, Curtin NJ. (2006)
Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441.
Cancer Res, 66 (10): 5354-62. [PMID:16707462]