(S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16,21- dimetheno-1H,13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene- 1,3(2H)-dione (LY333531) and related analogues: Isozyme selective inhibitors of protein kinase Cβ

Journal of Medicinal Chemistry

Volumn 39, Issue 14, 1996, Pages 2664-2671

  Jirousek, Michael R ^a   Gillig, James R ^a   Gonzalez, Cecile M ^a   Heath, William F ^a   McDonald III, John H ^a   Neel, David A ^a   Rito, Christopher J ^a   Singh, Upinder ^a   Stramm, Lawrence E ^a   Melikian Badalian, Anita ^b   Baevsky, Matthew ^b   Ballas, Lawrence M ^b   Hall, Steven E ^b   Winneroski, Leonard L ^a   Faul, Margaret M ^a  

^a ELI LILLY AND COMPANY   (United States)

^b Sphinx Pharmaceutical Corporation   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4BETA PHORBOL DIBUTYRATE; ADENOSINE TRIPHOSPHATE; CALMODULIN; CASEIN KINASE; CYCLIC AMP DEPENDENT PROTEIN KINASE; DIMETHYLAMINE; ISOENZYME; MALEIMIDE DERIVATIVE; PROTEIN KINASE C; PROTEIN KINASE C INHIBITOR; PROTEIN SERINE THREONINE KINASE; PROTEIN TYROSINE KINASE; RUBOXISTAURIN; STAUROSPORINE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CAPILLARY ENDOTHELIUM; CATTLE; DIABETIC RETINOPATHY; ENZYME INHIBITION; NONHUMAN; RETINA; STRUCTURE ACTIVITY RELATION;

AMINO ACID SEQUENCE; ANIMALS; CA(2+)-CALMODULIN DEPENDENT PROTEIN KINASE; CATTLE; CELLS, CULTURED; HUMANS; INDOLES; ISOENZYMES; MALEIMIDES; MOLECULAR SEQUENCE DATA; MOLECULAR STRUCTURE; PLASMINOGEN ACTIVATORS; PROTEIN KINASE C;

EID: 8944246315     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm950588y     Document Type: Article

References (49)

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36. Pile up comparison of the ATP regions of PKC can be obtained from the isoform sequences that are available from the following: (a) Chang, J. D.; Xu, Y.; Raychowdhury, M. K.; Ware, J. A. Molecular cloning and expression of a cDNA encoding a novel isoenzyme of protein kinase C (nPKC). J. Biol. Chem. 1993, 268, 14208-14214. (b) Finkenzeller, G.; Marme, D.; Hug, H. Sequence of human protein kinase Ca. Nucleic Acids Res. 1990, 18, 2183-2183. (c) Kubo, K.; Ohno, S.; Suzuki, K. Primary structures of protein kinase C bl and bll differ only in their C-terminal sequences. FEBS Lett. 1987, 223, 138-142. (d) Coussens, L.; Parker, P. J.; Rhee, L.; Yand-Feng, T. L.; Chen, E.; Waterfield, M. D.; Francke, U.; Ullrich, A. Multiple distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways. Science 1986, 233, 859-866. (e) Aris, J. P.; Basta, P. V.; Holmes, W. D.; Ballas, L. M.; Moomaw, C.; Rankel, N. B.; Blobel, G.; Loomis, C. R.; Burns, D. J. Molecular and biochemical characterization of a recombinant human PKCδ family member. Biochem. Biophys. Acta 1993, 1174, 171-181. (f) Kochs, G.; Meyer, D.; Hug, H.; Marme, D.; Sarre, T. F. Activation and substrate specificity of the human protein kinase C α and ζ isoenzymes. Eur. J. Biochem. 1993, 276, 597-606. (g) Bacher, N.; Zisman, Y.; Berent, E.; Livneh, E. Isolation and characterization of the PKC-L, a new member of the protein kinase C related gene family specifically expressed in lung, skin, and heart. Mol. Cell. Biol. 1991, 11, 126-133. (h) Basta, P.; Strickland, M. B.; Holmes, W.; Loomis, C. R.; Ballas, L. M.; Burns, D. J. Sequence and expression of human protein kinase Ce. Biochim. Biophys. Acta 1992, 1132, 154-160.
37. Pile up comparison of the ATP regions of PKC can be obtained from the isoform sequences that are available from the following: (a) Chang, J. D.; Xu, Y.; Raychowdhury, M. K.; Ware, J. A. Molecular cloning and expression of a cDNA encoding a novel isoenzyme of protein kinase C (nPKC). J. Biol. Chem. 1993, 268, 14208-14214. (b) Finkenzeller, G.; Marme, D.; Hug, H. Sequence of human protein kinase Ca. Nucleic Acids Res. 1990, 18, 2183-2183. (c) Kubo, K.; Ohno, S.; Suzuki, K. Primary structures of protein kinase C bl and bll differ only in their C-terminal sequences. FEBS Lett. 1987, 223, 138-142. (d) Coussens, L.; Parker, P. J.; Rhee, L.; Yand-Feng, T. L.; Chen, E.; Waterfield, M. D.; Francke, U.; Ullrich, A. Multiple distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways. Science 1986, 233, 859-866. (e) Aris, J. P.; Basta, P. V.; Holmes, W. D.; Ballas, L. M.; Moomaw, C.; Rankel, N. B.; Blobel, G.; Loomis, C. R.; Burns, D. J. Molecular and biochemical characterization of a recombinant human PKCδ family member. Biochem. Biophys. Acta 1993, 1174, 171-181. (f) Kochs, G.; Meyer, D.; Hug, H.; Marme, D.; Sarre, T. F. Activation and substrate specificity of the human protein kinase C α and ζ isoenzymes. Eur. J. Biochem. 1993, 276, 597-606. (g) Bacher, N.; Zisman, Y.; Berent, E.; Livneh, E. Isolation and characterization of the PKC-L, a new member of the protein kinase C related gene family specifically expressed in lung, skin, and heart. Mol. Cell. Biol. 1991, 11, 126-133. (h) Basta, P.; Strickland, M. B.; Holmes, W.; Loomis, C. R.; Ballas, L. M.; Burns, D. J. Sequence and expression of human protein kinase Ce. Biochim. Biophys. Acta 1992, 1132, 154-160.
38. Pile up comparison of the ATP regions of PKC can be obtained from the isoform sequences that are available from the following: (a) Chang, J. D.; Xu, Y.; Raychowdhury, M. K.; Ware, J. A. Molecular cloning and expression of a cDNA encoding a novel isoenzyme of protein kinase C (nPKC). J. Biol. Chem. 1993, 268, 14208-14214. (b) Finkenzeller, G.; Marme, D.; Hug, H. Sequence of human protein kinase Ca. Nucleic Acids Res. 1990, 18, 2183-2183. (c) Kubo, K.; Ohno, S.; Suzuki, K. Primary structures of protein kinase C bl and bll differ only in their C-terminal sequences. FEBS Lett. 1987, 223, 138-142. (d) Coussens, L.; Parker, P. J.; Rhee, L.; Yand-Feng, T. L.; Chen, E.; Waterfield, M. D.; Francke, U.; Ullrich, A. Multiple distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways. Science 1986, 233, 859-866. (e) Aris, J. P.; Basta, P. V.; Holmes, W. D.; Ballas, L. M.; Moomaw, C.; Rankel, N. B.; Blobel, G.; Loomis, C. R.; Burns, D. J. Molecular and biochemical characterization of a recombinant human PKCδ family member. Biochem. Biophys. Acta 1993, 1174, 171-181. (f) Kochs, G.; Meyer, D.; Hug, H.; Marme, D.; Sarre, T. F. Activation and substrate specificity of the human protein kinase C α and ζ isoenzymes. Eur. J. Biochem. 1993, 276, 597-606. (g) Bacher, N.; Zisman, Y.; Berent, E.; Livneh, E. Isolation and characterization of the PKC-L, a new member of the protein kinase C related gene family specifically expressed in lung, skin, and heart. Mol. Cell. Biol. 1991, 11, 126-133. (h) Basta, P.; Strickland, M. B.; Holmes, W.; Loomis, C. R.; Ballas, L. M.; Burns, D. J. Sequence and expression of human protein kinase Ce. Biochim. Biophys. Acta 1992, 1132, 154-160.
39. Pile up comparison of the ATP regions of PKC can be obtained from the isoform sequences that are available from the following: (a) Chang, J. D.; Xu, Y.; Raychowdhury, M. K.; Ware, J. A. Molecular cloning and expression of a cDNA encoding a novel isoenzyme of protein kinase C (nPKC). J. Biol. Chem. 1993, 268, 14208-14214. (b) Finkenzeller, G.; Marme, D.; Hug, H. Sequence of human protein kinase Ca. Nucleic Acids Res. 1990, 18, 2183-2183. (c) Kubo, K.; Ohno, S.; Suzuki, K. Primary structures of protein kinase C bl and bll differ only in their C-terminal sequences. FEBS Lett. 1987, 223, 138-142. (d) Coussens, L.; Parker, P. J.; Rhee, L.; Yand-Feng, T. L.; Chen, E.; Waterfield, M. D.; Francke, U.; Ullrich, A. Multiple distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways. Science 1986, 233, 859-866. (e) Aris, J. P.; Basta, P. V.; Holmes, W. D.; Ballas, L. M.; Moomaw, C.; Rankel, N. B.; Blobel, G.; Loomis, C. R.; Burns, D. J. Molecular and biochemical characterization of a recombinant human PKCδ family member. Biochem. Biophys. Acta 1993, 1174, 171-181. (f) Kochs, G.; Meyer, D.; Hug, H.; Marme, D.; Sarre, T. F. Activation and substrate specificity of the human protein kinase C α and ζ isoenzymes. Eur. J. Biochem. 1993, 276, 597-606. (g) Bacher, N.; Zisman, Y.; Berent, E.; Livneh, E. Isolation and characterization of the PKC-L, a new member of the protein kinase C related gene family specifically expressed in lung, skin, and heart. Mol. Cell. Biol. 1991, 11, 126-133. (h) Basta, P.; Strickland, M. B.; Holmes, W.; Loomis, C. R.; Ballas, L. M.; Burns, D. J. Sequence and expression of human protein kinase Ce. Biochim. Biophys. Acta 1992, 1132, 154-160.
40. Pile up comparison of the ATP regions of PKC can be obtained from the isoform sequences that are available from the following: (a) Chang, J. D.; Xu, Y.; Raychowdhury, M. K.; Ware, J. A. Molecular cloning and expression of a cDNA encoding a novel isoenzyme of protein kinase C (nPKC). J. Biol. Chem. 1993, 268, 14208-14214. (b) Finkenzeller, G.; Marme, D.; Hug, H. Sequence of human protein kinase Ca. Nucleic Acids Res. 1990, 18, 2183-2183. (c) Kubo, K.; Ohno, S.; Suzuki, K. Primary structures of protein kinase C bl and bll differ only in their C-terminal sequences. FEBS Lett. 1987, 223, 138-142. (d) Coussens, L.; Parker, P. J.; Rhee, L.; Yand-Feng, T. L.; Chen, E.; Waterfield, M. D.; Francke, U.; Ullrich, A. Multiple distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways. Science 1986, 233, 859-866. (e) Aris, J. P.; Basta, P. V.; Holmes, W. D.; Ballas, L. M.; Moomaw, C.; Rankel, N. B.; Blobel, G.; Loomis, C. R.; Burns, D. J. Molecular and biochemical characterization of a recombinant human PKCδ family member. Biochem. Biophys. Acta 1993, 1174, 171-181. (f) Kochs, G.; Meyer, D.; Hug, H.; Marme, D.; Sarre, T. F. Activation and substrate specificity of the human protein kinase C α and ζ isoenzymes. Eur. J. Biochem. 1993, 276, 597-606. (g) Bacher, N.; Zisman, Y.; Berent, E.; Livneh, E. Isolation and characterization of the PKC-L, a new member of the protein kinase C related gene family specifically expressed in lung, skin, and heart. Mol. Cell. Biol. 1991, 11, 126-133. (h) Basta, P.; Strickland, M. B.; Holmes, W.; Loomis, C. R.; Ballas, L. M.; Burns, D. J. Sequence and expression of human protein kinase Ce. Biochim. Biophys. Acta 1992, 1132, 154-160.
41. Pile up comparison of the ATP regions of PKC can be obtained from the isoform sequences that are available from the following: (a) Chang, J. D.; Xu, Y.; Raychowdhury, M. K.; Ware, J. A. Molecular cloning and expression of a cDNA encoding a novel isoenzyme of protein kinase C (nPKC). J. Biol. Chem. 1993, 268, 14208-14214. (b) Finkenzeller, G.; Marme, D.; Hug, H. Sequence of human protein kinase Ca. Nucleic Acids Res. 1990, 18, 2183-2183. (c) Kubo, K.; Ohno, S.; Suzuki, K. Primary structures of protein kinase C bl and bll differ only in their C-terminal sequences. FEBS Lett. 1987, 223, 138-142. (d) Coussens, L.; Parker, P. J.; Rhee, L.; Yand-Feng, T. L.; Chen, E.; Waterfield, M. D.; Francke, U.; Ullrich, A. Multiple distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways. Science 1986, 233, 859-866. (e) Aris, J. P.; Basta, P. V.; Holmes, W. D.; Ballas, L. M.; Moomaw, C.; Rankel, N. B.; Blobel, G.; Loomis, C. R.; Burns, D. J. Molecular and biochemical characterization of a recombinant human PKCδ family member. Biochem. Biophys. Acta 1993, 1174, 171-181. (f) Kochs, G.; Meyer, D.; Hug, H.; Marme, D.; Sarre, T. F. Activation and substrate specificity of the human protein kinase C α and ζ isoenzymes. Eur. J. Biochem. 1993, 276, 597-606. (g) Bacher, N.; Zisman, Y.; Berent, E.; Livneh, E. Isolation and characterization of the PKC-L, a new member of the protein kinase C related gene family specifically expressed in lung, skin, and heart. Mol. Cell. Biol. 1991, 11, 126-133. (h) Basta, P.; Strickland, M. B.; Holmes, W.; Loomis, C. R.; Ballas, L. M.; Burns, D. J. Sequence and expression of human protein kinase Ce. Biochim. Biophys. Acta 1992, 1132, 154-160.
42. Pile up comparison of the ATP regions of PKC can be obtained from the isoform sequences that are available from the following: (a) Chang, J. D.; Xu, Y.; Raychowdhury, M. K.; Ware, J. A. Molecular cloning and expression of a cDNA encoding a novel isoenzyme of protein kinase C (nPKC). J. Biol. Chem. 1993, 268, 14208-14214. (b) Finkenzeller, G.; Marme, D.; Hug, H. Sequence of human protein kinase Ca. Nucleic Acids Res. 1990, 18, 2183-2183. (c) Kubo, K.; Ohno, S.; Suzuki, K. Primary structures of protein kinase C bl and bll differ only in their C-terminal sequences. FEBS Lett. 1987, 223, 138-142. (d) Coussens, L.; Parker, P. J.; Rhee, L.; Yand-Feng, T. L.; Chen, E.; Waterfield, M. D.; Francke, U.; Ullrich, A. Multiple distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways. Science 1986, 233, 859-866. (e) Aris, J. P.; Basta, P. V.; Holmes, W. D.; Ballas, L. M.; Moomaw, C.; Rankel, N. B.; Blobel, G.; Loomis, C. R.; Burns, D. J. Molecular and biochemical characterization of a recombinant human PKCδ family member. Biochem. Biophys. Acta 1993, 1174, 171-181. (f) Kochs, G.; Meyer, D.; Hug, H.; Marme, D.; Sarre, T. F. Activation and substrate specificity of the human protein kinase C α and ζ isoenzymes. Eur. J. Biochem. 1993, 276, 597-606. (g) Bacher, N.; Zisman, Y.; Berent, E.; Livneh, E. Isolation and characterization of the PKC-L, a new member of the protein kinase C related gene family specifically expressed in lung, skin, and heart. Mol. Cell. Biol. 1991, 11, 126-133. (h) Basta, P.; Strickland, M. B.; Holmes, W.; Loomis, C. R.; Ballas, L. M.; Burns, D. J. Sequence and expression of human protein kinase Ce. Biochim. Biophys. Acta 1992, 1132, 154-160.
43. Pile up comparison of the ATP regions of PKC can be obtained from the isoform sequences that are available from the following: (a) Chang, J. D.; Xu, Y.; Raychowdhury, M. K.; Ware, J. A. Molecular cloning and expression of a cDNA encoding a novel isoenzyme of protein kinase C (nPKC). J. Biol. Chem. 1993, 268, 14208-14214. (b) Finkenzeller, G.; Marme, D.; Hug, H. Sequence of human protein kinase Ca. Nucleic Acids Res. 1990, 18, 2183-2183. (c) Kubo, K.; Ohno, S.; Suzuki, K. Primary structures of protein kinase C bl and bll differ only in their C-terminal sequences. FEBS Lett. 1987, 223, 138-142. (d) Coussens, L.; Parker, P. J.; Rhee, L.; Yand-Feng, T. L.; Chen, E.; Waterfield, M. D.; Francke, U.; Ullrich, A. Multiple distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways. Science 1986, 233, 859-866. (e) Aris, J. P.; Basta, P. V.; Holmes, W. D.; Ballas, L. M.; Moomaw, C.; Rankel, N. B.; Blobel, G.; Loomis, C. R.; Burns, D. J. Molecular and biochemical characterization of a recombinant human PKCδ family member. Biochem. Biophys. Acta 1993, 1174, 171-181. (f) Kochs, G.; Meyer, D.; Hug, H.; Marme, D.; Sarre, T. F. Activation and substrate specificity of the human protein kinase C α and ζ isoenzymes. Eur. J. Biochem. 1993, 276, 597-606. (g) Bacher, N.; Zisman, Y.; Berent, E.; Livneh, E. Isolation and characterization of the PKC-L, a new member of the protein kinase C related gene family specifically expressed in lung, skin, and heart. Mol. Cell. Biol. 1991, 11, 126-133. (h) Basta, P.; Strickland, M. B.; Holmes, W.; Loomis, C. R.; Ballas, L. M.; Burns, D. J. Sequence and expression of human protein kinase Ce. Biochim. Biophys. Acta 1992, 1132, 154-160.
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