An anticancer C-Kit kinase inhibitor is reengineered to make it more active and less cardiotoxic

Journal of Clinical Investigation

Volumn 117, Issue 12, 2007, Pages 4044-4054

  Fernández, Ariel ^a,b,f   Sanguino, Angela ^b   Peng, Zhenghong ^b   Ozturk, Eylem ^b,c   Chen, Jianping ^a   Crespo, Alejandro ^a   Wulf, Sarah ^a   Shavrin, Aleksander ^b   Qin, Chaoping ^d   Ma, Jianpeng ^a,d   Trent, Jonathan ^b   Lin, Yvonne ^b   Han, Hee Dong ^b   Mangala, Lingegowda S ^b   Bankson, James A ^b   Gelovani, Juri ^b   Samarel, Allen ^e   Bornmann, William ^b   Sood, Anil K ^b   Lopez Berestein, Gabriel ^b  

^a RICE UNIVERSITY   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^c HACETTEPE UNIVERSITY   (Turkey)

^d BAYLOR COLLEGE OF MEDICINE   (United States)

^e LOYOLA UNIVERSITY MEDICAL CENTER   (United States)

^f RICE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BCR ABL PROTEIN; IMATINIB; STRESS ACTIVATED PROTEIN KINASE;

ANIMAL EXPERIMENT; ARTICLE; CARDIOTOXICITY; COLORIMETRY; CONTROLLED STUDY; DENSITOMETRY; DRUG SPECIFICITY; FEMALE; IN VITRO STUDY; MOLECULAR DYNAMICS; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SPECTROMETRY;

ANIMALS; CARDIOTOXINS; DRUG SCREENING ASSAYS, ANTITUMOR; GASTROINTESTINAL STROMAL TUMORS; HEART DISEASES; HUMANS; K562 CELLS; MAP KINASE KINASE 4; NEOPLASMS, EXPERIMENTAL; PIPERAZINES; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; PROTO-ONCOGENE PROTEINS C-KIT; PYRIMIDINES; RATS; RATS, SPRAGUE-DAWLEY;

EID: 36849056267     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI32373     Document Type: Article

References (34)

1. Dancey, J., and Sausville, E.A. 2003. Issues and progress with protein kinase inhibitors for cancer treatment. Nat. Rev. Drug Discov. 2:296-313.
2. Levitski, A., and Gazit, A. 1995. Tyrosine kinase inhibition: an approach to drug development. Science. 267:1782-1788.
3. Tibes, R., Trent, J., and Kurzrock, R. 2005. Tyrosine kinase inhibitors and the dawn of molecular cancer therapeutics. Annu. Rev. Pharmacol. Toxicol. 45:357-384.
4. Gibbs, J., and Oliff, A. 1994. Pharmaceutical research in molecular oncology. Cell. 79:193-198.
5. Donato, N.J., and Talpaz, M. 2000. Clinical use of tyrosine kinase inhibitors: therapy for chronic myelogenous leukemia and other cancers. Clin. Cancer Res. 6:2965-2966.
6. Fabian, M.A., et al. 2005. A small molecule kinase interaction map for clinical kinase inhibitors. Nat. Biotechnol. 23:329-336.
7. Gambacorti-Passerini, C., et al. 1997. Inhibition of the ABL kinase activity blocks the proliferation of BCR/ABL+ leukemic cells and induces apoptosis. Blood Cells Mol. Dis. 23:380-394.
8. Schindler, T., et al. 2000. Structural mechanism for STI-571 inhibition of Abelson tyrosine kinase. Science. 289:1938-1942.
9. Attoub, S., et al. 2002. The c-kit tyrosine kinase inhibitor STI-571 for colorectal cancer therapy. Cancer Res. 62:4879-4883.
10. DeMatteo, R.P. 2002. The GIST of targeted cancer therapy: a tumor (gastrointestinal stromal tumor), a mutated gene (c-kit), and a molecular inhibitor (STI571). Ann. Surg. Oncol. 9:831-839.
11. Skene, R.J., et al. 2004. Structural basis for autoinhibition and STI-571 inhibition of C-kit Tyrosine kinase. J. Biol. Chem. 279:31655- 31663.
12. Tuveson, D.A., et al. 2001. STI571 inactivation of the gastrointestinal stromal tumor c-Kit oncoprotein: biological and clinical implications. Oncogene. 20:5054-5058.
13. Chen, J.P., Zhang, X., and Fernández, A. 2007. Molecular basis for specificity in the druggable kinome: sequence-based analysis. Bioinformatics. 23:563-572.
14. Knight, Z.A., and Shokat, K.M. 2005. Features of selective kinase inhibitors. Chem. Biol. 12:621-637.
15. Kerkela, R., et al. 2006. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat. Med. 12:908-916.
16. Druker, B.J. 2004. Molecularly targeted therapy: have the floodgates opened? Oncologist. 9:357-360.
17. Fernández, A., and Scheraga, H.A. 2003. Insufficiently dehydrated hydrogen bonds as determinants of protein interactions. Proc. Natl. Acad. Sci. U. S. A. 100:113-118.
18. 60c-src tyrosine kinase activities using a continuous assay: autoactivation of the enzyme is an intermolecular autophosphorylation process. Biochemistry. 34:14843-14851.
19. Songyang, Z., et al. 1995. Catalytic specificity of protein-tyrosine kinases is critical for selective signalling. Nature. 373:536-539.
20. Clarkson, B., Strife, A., Wisniewski, D., Lambek, C.L. and Liu, C. 2003. Chronic myelogenous leukemia as a paradigm of early cancer and possible curative strategy. Leukemia. 17:1211-1262.
21. Estey, E.H., et al. 1999. Molecular remissions induced by liposomal-encapsulated all-trans retinoic acid in newly diagnosed acute promyelocytic leukemia. Blood. 94:2230-2235.
22. Dorey, K, et al. 2001. Phosphorylation and structure-based functional studies reveal a positive and a negative role for the activation loop of the c-Abl tyrosine kinase. Oncogene. 20:8075-8081.
23. Prenen, H., Deroose, C., Vermaelen, P., Sciot, R., and Debiec-Rychter, M. 2006. Establishment of a mouse gastrointestinal stromal tumour model and evaluation of response to Imatinib by small animal positron emission tomography. Anticancer Res. 26:1247-1252.
24. Baines, C.P., and Molkentin, J.D. 2005. Stress signaling pathways that modulate cardiac myocyte apoptosis. J. Mol. Cell. Cardiol. 38:47-62.
25. Scheuermann-Freestone, M., et al. 2001. A new model of congestive heart failure in the mouse due to chronic volume overload. Eur. J. Heart Fail. 3:535-543.
26. Verweij, J., et al. 2007. Imatinib does not induce cardiac left ventricular failure in gastrointestinal stromal tumours patients: analysis of EORTC-ISG-AGITG study 62005. Eur. J. Cancer. 43:974-978.
27. Brooks, C.L., III, and Karplus, M. 1989. Solvent effects on protein motion and protein effects on solvent motion: dynamics of the active site region of lysozyme. J. Mol. Biol. 208:159-181.
28. Brooks, B.R. 1983. CHARMM: a program for macromolecular energy, minimization, and dynamics calculations. J. Comput. Chem. 4:187-217.
29. Neria, E., Fischer, S., and Karplus, M. 1996. Simulation of activation free energies in molecular systems. J. Chem. Phys. 105:1902-1921.
30. Jorgensen, W.L. 1981. Transferable intermolecular potential functions for water, alcohols, and ethers. Application to liquid water. J. Am. Chem. Soc. 103:335-340.
31. Timokhina, I., Kissel, H., Stella, G., and Besmer, P. 1998. Kit signaling through PI 3-kinase and Src kinase pathways: an essential role for Rac1 and JNK activation in mast cell proliferation. EMBO J. 17:6250-6262.
32. Samarel, A.M., and Engelmann, G.L. 1991. Contractile activity modulates myosin heavy chain-β expression in neonatal rat heart cells. Am. J. Physiol. 261:H1067-H1077.
33. Schlaepfer, D.D., and Hunter, T. 1996. Evidence for in vivo phosphorylation of the Grb2 SH2-domain binding site on focal adhesion kinase by Src-family protein-tyrosine kinases. Mol. Cell. Biol. 16:5623-5633.
34. Thaker, P.H., et al. 2006. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat. Med. 12:939-944.