compound 22 [PMID: 21823616]   Click here for help

GtoPdb Ligand ID: 8116

Compound class: Synthetic organic
Comment: Compound 22 was a lead reported as the result of a compound screen for inhibitors of the protein kinase integrin-linked kinase (ILK) [9].
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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

compound 22 [PMID: 21823616] 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 5
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 61.67
Molecular weight 533.24
XLogP 6.05
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 CNC(=O)CCc1nn(c(c1)c1ccc(cc1)c1ccc(cc1)C(F)(F)F)c1ccc(cc1)N1CCNCC1
Isomeric SMILES CNC(=O)CCc1nn(c(c1)c1ccc(cc1)c1ccc(cc1)C(F)(F)F)c1ccc(cc1)N1CCNCC1
InChI InChI=1S/C30H30F3N5O/c1-34-29(39)15-10-25-20-28(38(36-25)27-13-11-26(12-14-27)37-18-16-35-17-19-37)23-4-2-21(3-5-23)22-6-8-24(9-7-22)30(31,32)33/h2-9,11-14,20,35H,10,15-19H2,1H3,(H,34,39)
InChI Key GHBUPSVATJKTRR-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. Ahmed N, Riley C, Oliva K, Stutt E, Rice GE, Quinn MA. (2003)
Integrin-linked kinase expression increases with ovarian tumour grade and is sustained by peritoneal tumour fluid.
J Pathol, 201 (2): 229-37. [PMID:14517840]
2. Bravou V, Klironomos G, Papadaki E, Taraviras S, Varakis J. (2006)
ILK over-expression in human colon cancer progression correlates with activation of beta-catenin, down-regulation of E-cadherin and activation of the Akt-FKHR pathway.
J Pathol, 208 (1): 91-9. [PMID:16278819]
3. Chan J, Ko FC, Yeung YS, Ng IO, Yam JW. (2011)
Integrin-linked kinase overexpression and its oncogenic role in promoting tumorigenicity of hepatocellular carcinoma.
PLoS ONE, 6 (2): e16984. [PMID:21347395]
4. Delcommenne M, Tan C, Gray V, Rue L, Woodgett J, Dedhar S. (1998)
Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase.
Proc Natl Acad Sci USA, 95 (19): 11211-6. [PMID:9736715]
5. Deng JT, Sutherland C, Brautigan DL, Eto M, Walsh MP. (2002)
Phosphorylation of the myosin phosphatase inhibitors, CPI-17 and PHI-1, by integrin-linked kinase.
Biochem J, 367 (Pt 2): 517-24. [PMID:12144526]
6. Deng JT, Van Lierop JE, Sutherland C, Walsh MP. (2001)
Ca2+-independent smooth muscle contraction. a novel function for integrin-linked kinase.
J Biol Chem, 276 (19): 16365-73. [PMID:11278951]
7. Graff JR, Deddens JA, Konicek BW, Colligan BM, Hurst BM, Carter HW, Carter JH. (2001)
Integrin-linked kinase expression increases with prostate tumor grade.
Clin Cancer Res, 7 (7): 1987-91. [PMID:11448915]
8. Ito R, Oue N, Zhu X, Yoshida K, Nakayama H, Yokozaki H, Yasui W. (2003)
Expression of integrin-linked kinase is closely correlated with invasion and metastasis of gastric carcinoma.
Virchows Arch, 442 (2): 118-23. [PMID:12596061]
9. Lee SL, Hsu EC, Chou CC, Chuang HC, Bai LY, Kulp SK, Chen CS. (2011)
Identification and characterization of a novel integrin-linked kinase inhibitor.
J Med Chem, 54 (18): 6364-74. [PMID:21823616]
10. Persad S, Attwell S, Gray V, Delcommenne M, Troussard A, Sanghera J, Dedhar S. (2000)
Inhibition of integrin-linked kinase (ILK) suppresses activation of protein kinase B/Akt and induces cell cycle arrest and apoptosis of PTEN-mutant prostate cancer cells.
Proc Natl Acad Sci USA, 97 (7): 3207-12. [PMID:10716737]
11. Persad S, Attwell S, Gray V, Mawji N, Deng JT, Leung D, Yan J, Sanghera J, Walsh MP, Dedhar S. (2001)
Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343.
J Biol Chem, 276 (29): 27462-9. [PMID:11313365]
12. Pontier SM, Huck L, White DE, Rayment J, Sanguin-Gendreau V, Hennessy B, Zuo D, St-Arnaud R, Mills GB, Dedhar S et al.. (2010)
Integrin-linked kinase has a critical role in ErbB2 mammary tumor progression: implications for human breast cancer.
Oncogene, 29 (23): 3374-85. [PMID:20305688]
13. Schaeffer DF, Assi K, Chan K, Buczkowski AK, Chung SW, Scudamore CH, Weiss A, Salh B, Owen DA. (2010)
Tumor expression of integrin-linked kinase (ILK) correlates with the expression of the E-cadherin repressor snail: an immunohistochemical study in ductal pancreatic adenocarcinoma.
Virchows Arch, 456 (3): 261-8. [PMID:20091050]
14. Troussard AA, Mawji NM, Ong C, Mui A, St -Arnaud R, Dedhar S. (2003)
Conditional knock-out of integrin-linked kinase demonstrates an essential role in protein kinase B/Akt activation.
J Biol Chem, 278 (25): 22374-8. [PMID:12686550]