compound 30 [PMID: 23414845]   Click here for help

GtoPdb Ligand ID: 7864

PDB Ligand
Compound class: Synthetic organic
Comment: Compound 30 [7] is a selective inhibitor of the tyrosine kinase PTK2 (aka FAK). It is a type III inhibitor, meaning that it binds to an allosteric site, not to the ATP active site of the kinase.
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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 5
Hydrogen bond donors 1
Rotatable bonds 4
Topological polar surface area 75.61
Molecular weight 410.18
XLogP 5.15
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 Cn1ncc2c1c1cc(NCc3ccc(cc3)C(C)(C)C)ccc1N(S2(=O)=O)C
Isomeric SMILES Cn1ncc2c1c1cc(NCc3ccc(cc3)C(C)(C)C)ccc1N(S2(=O)=O)C
InChI InChI=1S/C22H26N4O2S/c1-22(2,3)16-8-6-15(7-9-16)13-23-17-10-11-19-18(12-17)21-20(14-24-25(21)4)29(27,28)26(19)5/h6-12,14,23H,13H2,1-5H3
InChI Key AVFJKWOKOZKXRX-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. Halder J, Kamat AA, Landen Jr CN, Han LY, Lutgendorf SK, Lin YG, Merritt WM, Jennings NB, Chavez-Reyes A, Coleman RL et al.. (2006)
Focal adhesion kinase targeting using in vivo short interfering RNA delivery in neutral liposomes for ovarian carcinoma therapy.
Clin Cancer Res, 12 (16): 4916-24. [PMID:16914580]
2. Ilić D, Furuta Y, Kanazawa S, Takeda N, Sobue K, Nakatsuji N, Nomura S, Fujimoto J, Okada M, Yamamoto T. (1995)
Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice.
Nature, 377 (6549): 539-44. [PMID:7566154]
3. McLean GW, Carragher NO, Avizienyte E, Evans J, Brunton VG, Frame MC. (2005)
The role of focal-adhesion kinase in cancer - a new therapeutic opportunity.
Nat Rev Cancer, 5 (7): 505-15. [PMID:16069815]
4. Schlaepfer DD, Hanks SK, Hunter T, van der Geer P. (1994)
Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase.
Nature, 372 (6508): 786-91. [PMID:7997267]
5. Schwock J, Dhani N, Cao MP, Zheng J, Clarkson R, Radulovich N, Navab R, Horn LC, Hedley DW. (2009)
Targeting focal adhesion kinase with dominant-negative FRNK or Hsp90 inhibitor 17-DMAG suppresses tumor growth and metastasis of SiHa cervical xenografts.
Cancer Res, 69 (11): 4750-9. [PMID:19458065]
6. Schwock J, Dhani N, Hedley DW. (2010)
Targeting focal adhesion kinase signaling in tumor growth and metastasis.
Expert Opin Ther Targets, 14 (1): 77-94. [PMID:20001212]
7. Tomita N, Hayashi Y, Suzuki S, Oomori Y, Aramaki Y, Matsushita Y, Iwatani M, Iwata H, Okabe A, Awazu Y et al.. (2013)
Structure-based discovery of cellular-active allosteric inhibitors of FAK.
Bioorg Med Chem Lett, 23 (6): 1779-85. [PMID:23414845]
8. Tsutsumi K, Yamaura T, Nakajima M, Honda T, Kasaoka T. (2009)
Silencing of focal adhesion kinase by tumor direct injection of small interfering RNA decreases in vivo tumor growth.
Cancer Biol Ther, 8 (13): 1292-9. [PMID:19458494]