KU-0060648   Click here for help

GtoPdb Ligand ID: 8011

Synonyms: KU 0060648
Compound class: Synthetic organic
Comment: KU-0060648 is a dual inhibitor of DNA dependent protein kinase (DNA-PK) and the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) α, β and δ subunits. This compound is an analogue of NU-7441 with improved solubility and potency, and additional activity against PI3Ks [1]. This is compound 39 in Cano et al. (2013) [1].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 1
Rotatable bonds 7
Topological polar surface area 106.5
Molecular weight 582.23
XLogP 5.92
No. Lipinski's rules broken 1
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Canonical SMILES CCN1CCN(CC1)CC(=O)Nc1ccc(c2c1c1ccccc1s2)c1cccc2c1oc(cc2=O)N1CCOCC1
Isomeric SMILES CCN1CCN(CC1)CC(=O)Nc1ccc(c2c1c1ccccc1s2)c1cccc2c1oc(cc2=O)N1CCOCC1
InChI InChI=1S/C33H34N4O4S/c1-2-35-12-14-36(15-13-35)21-29(39)34-26-11-10-23(33-31(26)25-6-3-4-9-28(25)42-33)22-7-5-8-24-27(38)20-30(41-32(22)24)37-16-18-40-19-17-37/h3-11,20H,2,12-19,21H2,1H3,(H,34,39)
1. Cano C, Saravanan K, Bailey C, Bardos J, Curtin NJ, Frigerio M, Golding BT, Hardcastle IR, Hummersone MG, Menear KA et al.. (2013)
1-substituted (Dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-ones endowed with dual DNA-PK/PI3-K inhibitory activity.
J Med Chem, 56 (16): 6386-401. [PMID:23855836]
2. 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]
3. Munck JM, Batey MA, Zhao Y, Jenkins H, Richardson CJ, Cano C, Tavecchio M, Barbeau J, Bardos J, Cornell L et al.. (2012)
Chemosensitization of cancer cells by KU-0060648, a dual inhibitor of DNA-PK and PI-3K.
Mol Cancer Ther, 11 (8): 1789-98. [PMID:22576130]
4. 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]
5. Smith GC, Jackson SP. (1999)
The DNA-dependent protein kinase.
Genes Dev, 13 (8): 916-34. [PMID:10215620]
6. 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]