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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2D Structure
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Physico-chemical Properties
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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
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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)
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]