Target Validation Information
Target ID T47107
Target Name Protein kinase C gamma type
Target Type
Successful
Drug Potency against Target Midostaurin Drug Info IC50 = 10 nM [552773]
LY-326449 Drug Info IC50 = 630 nM [534154]
8-Octyl-benzolactam-V9 Drug Info Ki = 5200 nM [528158]
RO-320432 Drug Info IC50 = 36.5 nM
[2,2':5',2'']Terthiophen-4-yl-methanol Drug Info IC50 = 3000 nM [525575]
GF-109203 Drug Info IC50 = 30 nM [529049]
BALANOL Drug Info IC50 = 30 nM
PROSTRATIN Drug Info Ki = 12.5 nM [527606]
[2,2':5',2'']Terthiophene-4,5''-dicarbaldehyde Drug Info IC50 = 700 nM [525575]
[2,2':5',2'']Terthiophene-4-carbaldehyde Drug Info IC50 = 5000 nM [525575]
Ro-32-0557 Drug Info IC50 = 5.4 nM
LY-317644 Drug Info IC50 = 6400 nM
(-)-Cercosporamide Drug Info IC50 = 5800 nM [529887]
Indolocarbazole analogue Drug Info IC50 = 3 nM [526234]
RO-316233 Drug Info IC50 = 550 nM [528701]
Monoctanoin component C Drug Info Ki = 2930 nM
Action against Disease Model Midostaurin The effect of midostaurin on IgE-dependent mediator release in normal h uMan blood basophils and cultured cord blood cell-derived MC, and on spontaneous histamine secretion in the MC leukaemia cell line HMC-1 and the basophil cell line KU812 were studied. The effects of midostaurin on histamine release were dose-dependent and occurred at pharmacologic concentrations (IC(50) 10-100 nm). Midostaurin was also found to inhibit the IgE-dependent up-regulation of CD63 on cultured cord blood cell-derived h uMan MC, but did not inhibit IgE-dependent up-regulation of CD63 or CD203c in h uMan blood basophils. [552994] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations We examined the effects of different types of anesthetics on PKC-gamma knockout mice.Isoflurane (2.6%) and sevoflurane (3.4%) used at twice the minim uM alveolar concentration significantly prolonged the rtfLORRs in PKC-gamma knockout mice compared to those in wild-type mice. On the other hand, no significant difference was observed between knockout and wild-type mice treated with propofol (200 mg/kg). Examination of the cellular fractions isolated from volatile anesthetic-treated mouse brains showed that PKC-gamma was significantly decreased in the synaptic membrane fraction (P2), whereas p-PKC-gamma was significantly increased in P2. There was no significant change in the supernatant fraction (S). In propofol-treated mice, PKC-gamma and p-PKC-gamma showed no significant changes in P2 or S. [552773]
References
Ref 552773A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol. 2008 Jan;26(1):127-32. doi: 10.1038/nbt1358.
Ref 534154J Med Chem. 1996 Jul 5;39(14):2664-71.(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.
Ref 528158J Med Chem. 2006 May 4;49(9):2681-8.Design and synthesis of 8-octyl-benzolactam-V9, a selective activator for protein kinase C epsilon and eta.
Ref 525575Bioorg Med Chem Lett. 1999 Aug 2;9(15):2279-82.Novel protein kinase C inhibitors: synthesis and PKC inhibition of beta-substituted polythiophene derivatives.
Ref 529049J Biol Chem. 2007 Nov 9;282(45):33052-63. Epub 2007 Sep 17.Protein kinase C epsilon regulates gamma-aminobutyrate type A receptor sensitivity to ethanol and benzodiazepines through phosphorylation of gamma2 subunits.
Ref 552994Midostaurin (PKC412) inhibits immunoglobulin E-dependent activation and mediator release in human blood basophils and mast cells. Clin Exp Allergy. 2009 Nov;39(11):1711-20. doi: 10.1111/j.1365-2222.2009.03353.x.
Ref 527606J Med Chem. 1992 May 29;35(11):1978-86.A nonpromoting phorbol from the samoan medicinal plant Homalanthus nutans inhibits cell killing by HIV-1.
Ref 525575Bioorg Med Chem Lett. 1999 Aug 2;9(15):2279-82.Novel protein kinase C inhibitors: synthesis and PKC inhibition of beta-substituted polythiophene derivatives.
Ref 525575Bioorg Med Chem Lett. 1999 Aug 2;9(15):2279-82.Novel protein kinase C inhibitors: synthesis and PKC inhibition of beta-substituted polythiophene derivatives.
Ref 529887Bioorg Med Chem Lett. 2009 Feb 1;19(3):724-6. Epub 2008 Dec 11.(-)-Cercosporamide derivatives as novel antihyperglycemic agents.
Ref 526234Bioorg Med Chem Lett. 2002 Jan 21;12(2):147-50.Mixed lineage kinase activity of indolocarbazole analogues.
Ref 528701J Med Chem. 1992 Jan;35(1):177-84.Inhibitors of protein kinase C. 1. 2,3-Bisarylmaleimides.

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