1. AstraZeneca, Sweden

Abstract

PKCδ and PKCθ are PKC isoforms that are activated by diacylglycerol and may be inhibited by calphostin C, Gö 6983 and chelerythrine.

Contents

GtoPdb is an expert-driven guide to pharmacological targets and the substances that act on them. GtoPdb is a reference work which is most usefully represented as an on-line database. As in any publication this work should be appropriately cited, and the papers it cites should also be recognized. This document provides a citation for the relevant parts of the database, and also provides a reference list for the research cited by those parts. For further details see [5].

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References

1. Anastassiadis T, Deacon SW, Devarajan K, Ma H and Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol 29: 1039-45 [PMID:22037377]
2. Baier G, Telford D, Giampa L, Coggeshall KM, Baier-Bitterlich G, Isakov N and Altman A. (1993) Molecular cloning and characterization of PKC theta, a novel member of the protein kinase C (PKC) gene family expressed predominantly in hematopoietic cells. J Biol Chem 268: 4997-5004 [PMID:8444877]
3. Belot A, Kasher PR, Trotter EW, Foray AP, Debaud AL, Rice GI, Szynkiewicz M, Zabot MT, Rouvet I and Bhaskar SS et al.. (2013) Protein kinase cδ deficiency causes mendelian systemic lupus erythematosus with B cell-defective apoptosis and hyperproliferation. Arthritis Rheum 65: 2161-71 [PMID:23666743]
4. Birchall AM, Bishop J, Bradshaw D, Cline A, Coffey J, Elliott LH, Gibson VM, Greenham A, Hallam TJ and Harris W et al.. (1994) Ro 32-0432, a selective and orally active inhibitor of protein kinase C prevents T-cell activation. J Pharmacol Exp Ther 268: 922-9 [PMID:8114006]
5. Buneman P, Christie G, Davies JA, Dimitrellou R, Harding SD, Pawson AJ, Sharman JL and Wu Y. (2020) Why data citation isn't working, and what to do about it Database 2020 [PMID:32367113]
6. Chand S, Mehta N, Bahia MS, Dixit A and Silakari O. (2012) Protein kinase C-theta inhibitors: a novel therapy for inflammatory disorders. Curr Pharm Des 18: 4725-46 [PMID:22830352]
7. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK and Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol 29: 1046-51 [PMID:22037378]
8. Defauw JM, Murphy MM, Jagdmann Jr GE, Hu H, Lampe JW, Hollinshead SP, Mitchell TJ, Crane HM, Heerding JM and Mendoza JS et al.. (1996) Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs that are highly selective for protein kinase C over protein kinase A. J Med Chem 39: 5215-27 [PMID:8978850]
9. Faul MM, Gillig JR, Jirousek MR, Ballas LM, Schotten T, Kahl A and Mohr M. (2003) Acyclic N-(azacycloalkyl)bisindolylmaleimides: isozyme selective inhibitors of PKCbeta. Bioorg Med Chem Lett 13: 1857-9 [PMID:12749884]
10. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R and Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J 451: 313-28 [PMID:23398362]
11. Garcia LC, Donadío LG, Mann E, Kolusheva S, Kedei N, Lewin NE, Hill CS, Kelsey JS, Yang J and Esch TE et al.. (2014) Synthesis, biological, and biophysical studies of DAG-indololactones designed as selective activators of RasGRP. Bioorg Med Chem 22: 3123-40 [PMID:24794745]
12. George DM, Breinlinger EC, Friedman M, Zhang Y, Wang J, Argiriadi M, Bansal-Pakala P, Barth M, Duignan DB and Honore P et al.. (2015) Discovery of selective and orally bioavailable protein kinase Cθ (PKCθ) inhibitors from a fragment hit. J Med Chem 58: 222-36 [PMID:25000588]
13. Gschwendt M, Dieterich S, Rennecke J, Kittstein W, Mueller HJ and Johannes FJ. (1996) Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes. FEBS Lett 392: 77-80 [PMID:8772178]
14. Gschwendt M, Müller HJ, Kielbassa K, Zang R, Kittstein W, Rincke G and Marks F. (1994) Rottlerin, a novel protein kinase inhibitor. Biochem Biophys Res Commun 199: 93-8 [PMID:8123051]
15. Heerding DA, Rhodes N, Leber JD, Clark TJ, Keenan RM, Lafrance LV, Li M, Safonov IG, Takata DT and Venslavsky JW et al.. (2008) Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase. J Med Chem 51: 5663-79 [PMID:18800763]
16. Jirousek MR, Gillig JR, Gonzalez CM, Heath WF, McDonald JH, Neel DA, Rito CJ, Singh U, Stramm LE and Melikian-Badalian A et al.. (1996) (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)-d ione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase C beta. J Med Chem 39: 2664-71 [PMID:8709095]
17. Katoh T, Takai T, Yukawa T, Tsukamoto T, Watanabe E, Mototani H, Arita T, Hayashi H, Nakagawa H and Klein MG et al.. (2016) Discovery and optimization of 1,7-disubstituted-2,2-dimethyl-2,3-dihydroquinazolin-4(1H)-ones as potent and selective PKCθ inhibitors. Bioorg Med Chem 24: 2466-75 [PMID:27117263]
18. Kedei N, Lundberg DJ, Toth A, Welburn P, Garfield SH and Blumberg PM. (2004) Characterization of the interaction of ingenol 3-angelate with protein kinase C. Cancer Res 64: 3243-55 [PMID:15126366]
19. Kuehn HS, Niemela JE, Rangel-Santos A, Zhang M, Pittaluga S, Stoddard JL, Hussey AA, Evbuomwan MO, Priel DA and Kuhns DB et al.. (2013) Loss-of-function of the protein kinase C δ (PKCδ) causes a B-cell lymphoproliferative syndrome in humans. Blood 121: 3117-25 [PMID:23430113]
20. Kwon MJ, Wang R, Ma J and Sun Z. (2010) PKC-θ is a drug target for prevention of T cell-mediated autoimmunity and allograft rejection. Endocr Metab Immune Disord Drug Targets 10: 367-72 [PMID:20923402]
21. Ladduwahetty T, Lee MR, Maillard MC, Cachope R, Todd D, Barnes M, Beaumont V, Chauhan A, Gallati C and Haughan AF et al.. (2022) Identification of a Potent, Selective, and Brain-Penetrant Rho Kinase Inhibitor and its Activity in a Mouse Model of Huntington's Disease. J Med Chem [PMID:35816678]
22. Liu Y, Graham C, Parravicini V, Brown MJ, Rivera J and Shaw S. (2001) Protein kinase C theta is expressed in mast cells and is functionally involved in Fcepsilon receptor I signaling. J Leukoc Biol 69: 831-40 [PMID:11358993]
23. Luzzio MJ, Papillon J and Visser MS. (2016) Protein kinase C inhibitors and methods of their use Patent number: WO2016020864A1. Assignee: Novartis Ag. Priority date: 06/08/2014. Publication date: 11/02/2016.
24. Martiny-Baron G, Kazanietz MG, Mischak H, Blumberg PM, Kochs G, Hug H, Marmé D and Schächtele C. (1993) Selective inhibition of protein kinase C isozymes by the indolocarbazole Gö 6976. J Biol Chem 268: 9194-7 [PMID:8486620]
25. Monks CR, Kupfer H, Tamir I, Barlow A and Kupfer A. (1997) Selective modulation of protein kinase C-theta during T-cell activation. Nature 385: 83-6 [PMID:8985252]
26. Papa P, Whitefield B, Mortensen DS, Cashion D, Huang D, Torres E, Parnes J, Sapienza J, Hansen J and Correa M et al.. (2021) Discovery of the Selective Protein Kinase C-θ Kinase Inhibitor, CC-90005. J Med Chem [PMID:34355886]
27. Seynaeve CM, Kazanietz MG, Blumberg PM, Sausville EA and Worland PJ. (1994) Differential inhibition of protein kinase C isozymes by UCN-01, a staurosporine analogue. Mol Pharmacol 45: 1207-14 [PMID:8022414]
28. Tanaka M, Sagawa S, Hoshi J, Shimoma F, Matsuda I, Sakoda K, Sasase T, Shindo M and Inaba T. (2004) Synthesis of anilino-monoindolylmaleimides as potent and selective PKCbeta inhibitors. Bioorg Med Chem Lett 14: 5171-4 [PMID:15380221]
29. Toullec D, Pianetti P, Coste H, Bellevergue P, Grand-Perret T, Ajakane M, Baudet V, Boissin P, Boursier E and Loriolle F et al.. (1991) The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. J Biol Chem 266: 15771-81 [PMID:1874734]
30. Uddin M, Seumois G, Lau LC, Davies DE and Djukanovic R. (2006) Activation of neutrophils by the repairing epithelium is regulated via PI3-kinase/Akt/PKCdelta-mediated signals Thorax (BTS suppl 2) 61: S21
31. Vyas YM, Mehta KM, Morgan M, Maniar H, Butros L, Jung S, Burkhardt JK and Dupont B. (2001) Spatial organization of signal transduction molecules in the NK cell immune synapses during MHC class I-regulated noncytolytic and cytolytic interactions. J Immunol 167: 4358-67 [PMID:11591760]
32. Wagner J, von Matt P, Sedrani R, Albert R, Cooke N, Ehrhardt C, Geiser M, Rummel G, Stark W and Strauss A et al.. (2009) Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes. J Med Chem 52: 6193-6 [PMID:19827831]
33. Wilkinson SE, Parker PJ and Nixon JS. (1993) Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C. Biochem J 294 ( Pt 2): 335-7 [PMID:8373348]
34. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC and Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol 17: 1241-9 [PMID:21095574]
35. Xu ZB, Chaudhary D, Olland S, Wolfrom S, Czerwinski R, Malakian K, Lin L, Stahl ML, Joseph-McCarthy D and Benander C et al.. (2004) Catalytic domain crystal structure of protein kinase C-theta (PKCtheta). J Biol Chem 279: 50401-9 [PMID:15364937]
36. Zanin-Zhorov A, Dustin ML and Blazar BR. (2011) PKC-θ function at the immunological synapse: prospects for therapeutic targeting. Trends Immunol 32: 358-63 [PMID:21733754]