7-hydroxystaurosporine   Click here for help

GtoPdb Ligand ID: 7907

Synonyms: KRX-0601 | KRX0601 | UCN 01 | UCN-01
PDB Ligand
Compound class: Synthetic organic
Comment: 7-hydroxystaurosporine is a cell-permeable staurosporine derivative, with anticancer activity [6]. It reversibly and ATP-competitively inhibits multiple protein kinases, including PKCα, β, γ, δ and ε [5], Chk1 [1-3], Cdc25C-associated protein kinase 1 (cTAK1) [1], Cdk1 [2], PAK4, Cdk5/p25, Chk2 [1], PDK1 [4], Lck [2], p38 MAPK kinase 2 (MAPK14) [3], Akt, GSK-3β [2] and PKA [6].
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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
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 6
Hydrogen bond donors 3
Rotatable bonds 2
Topological polar surface area 89.68
Molecular weight 482.2
XLogP 5.58
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 CNC1CC2OC(C1OC)(C)n1c3ccccc3c3c1c1n2c2ccccc2c1c1c3C(NC1=O)O
Isomeric SMILES CN[C@@H]1C[C@H]2O[C@]([C@@H]1OC)(C)n1c3ccccc3c3c1c1n2c2ccccc2c1c1c3[C@H](NC1=O)O
InChI InChI=1S/C28H26N4O4/c1-28-25(35-3)15(29-2)12-18(36-28)31-16-10-6-4-8-13(16)19-21-22(27(34)30-26(21)33)20-14-9-5-7-11-17(14)32(28)24(20)23(19)31/h4-11,15,18,25,27,29,34H,12H2,1-3H3,(H,30,33)/t15-,18-,25-,27-,28+/m1/s1
InChI Key PBCZSGKMGDDXIJ-HQCWYSJUSA-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. Busby EC, Leistritz DF, Abraham RT, Karnitz LM, Sarkaria JN. (2000)
The radiosensitizing agent 7-hydroxystaurosporine (UCN-01) inhibits the DNA damage checkpoint kinase hChk1.
Cancer Res, 60 (8): 2108-12. [PMID:10786669]
2. Jiang X, Zhao B, Britton R, Lim LY, Leong D, Sanghera JS, Zhou BB, Piers E, Andersen RJ, Roberge M. (2004)
Inhibition of Chk1 by the G2 DNA damage checkpoint inhibitor isogranulatimide.
Mol Cancer Ther, 3 (10): 1221-7. [PMID:15486189]
3. Reinhardt HC, Aslanian AS, Lees JA, Yaffe MB. (2007)
p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage.
Cancer Cell, 11 (2): 175-89. [PMID:17292828]
4. Sato S, Fujita N, Tsuruo T. (2002)
Interference with PDK1-Akt survival signaling pathway by UCN-01 (7-hydroxystaurosporine).
Oncogene, 21 (11): 1727-38. [PMID:11896604]
5. Seynaeve CM, Kazanietz MG, Blumberg PM, Sausville EA, Worland PJ. (1994)
Differential inhibition of protein kinase C isozymes by UCN-01, a staurosporine analogue.
Mol Pharmacol, 45 (6): 1207-14. [PMID:8022414]
6. Takahashi I, Kobayashi E, Asano K, Yoshida M, Nakano H. (1987)
UCN-01, a selective inhibitor of protein kinase C from Streptomyces.
J Antibiot, 40 (12): 1782-4. [PMID:3429345]