Therapeutic Targets Database
BIDD Pharmainformatics Databases


Target Validation Information
Target NameProtein kinase C, alpha type    
Type of TargetClinical trial target    
Drug Potency against TargetSotrastaurin acetateKi = 0.22 nM[1]
Sotrastaurin acetateKi = 0.95 nM[2]
TANNIN analogueIC50 = 10000 nM[3]
(-)-CercosporamideIC50 = 1020 nM[4]
Dequalinium AnalogueIC50 = 11000 nM[5]
TANNIN analogueIC50 = 11000 nM[3]
TANNIN analogueIC50 = 12000 nM[3]
Plantainoside DIC50 = 14800 nM[6]
TANNIN analogueIC50 = 15000 nM[3]
Indolocarbazole analogueIC50 = 1600 nM[7]
TANNINIC50 = 16000 nM[3]
TANNINIC50 = 17000 nM[3]
Ro-32-0557IC50 = 2.85 nM[8]
TANNIN analogueIC50 = 2000 nM[3]
Indolocarbazole analogueIC50 = 222 nM[7]
Dequalinium AnalogueIC50 = 2600 nM[5]
Indolocarbazole analogueIC50 = 2600 nM[7]
Dequalinium AnalogueIC50 = 2800 nM[5]
Indolocarbazole analogueIC50 = 3 nM[7]
TANNIN analogueIC50 = 3000 nM[3]
[2,2';5',2'']Terthiophen-4-yl-methanolIC50 = 3000 nM[9]
Indolocarbazole analogueIC50 = 400 nM[7]
PUNICAFOLINIC50 = 4000 nM[3]
TANNIN analogueIC50 = 4000 nM[3]
TANNIN analogueIC50 = 4000 nM[3]
TANNIN analogueIC50 = 4000 nM[3]
Indolocarbazole analogueIC50 = 450 nM[7]
Dequalinium AnalogueIC50 = 5000 nM[5]
TANNIN analogueIC50 = 5000 nM[3]
[2,2';5',2'']Terthiophene-4-carbaldehydeIC50 = 5000 nM[9]
RO-316233IC50 = 550 nM[11]
LY-326449IC50 = 630 nM[12]
LY-317644IC50 = 6400 nM[13]
BALANOLIC50 = 70 nM[14]
[2,2';5',2'']Terthiophene-4,5''-dicarbaldehydeIC50 = 700 nM[9]
TANNIN analogueIC50 = 7000 nM[3]
3-(1H-Indol-3-yl)-4-phenylamino-pyrrole-2,5-dioneIC50 = 7233 nM[15]
RO-320432IC50 = 8.8 nM[8]
TANNIN analogueIC50 = 8000 nM[3]
TANNIN analogueIC50 = 8000 nM[3]
ACETOSIDEIC50 = 9300 nM[6]
Indolocarbazole analogueIC50 = 980 nM[7]
PROSTRATINKi = 12.5 nM[16]
diheptan-3-yl 5-(hydroxymethyl)isophthalateKi = 319 nM[17]
1,2-dioctanoyl-sn-glycerolKi = 40.1 nM[17]
dihexan-3-yl 5-(hydroxymethyl)isophthalateKi = 661 nM[17]
Action against Disease ModelSotrastaurin acetateTotal protein kinase C (PKC) activity and the expression of 9 isoforms were determined in the estrogen receptor (ER) positive MCF-7 h uMan breast cancer cell line, this line transfected to overexpress either PKC-Ø¢ or erbB2, and in 3 ER negative breast cancer cell lines.[18]
The Effect of Target Knockout, Knockdown or Genetic VariationsThe Prkca(-/-) mice showed no signs of retinal degeneration up to 12 months of age, but ERG measurements indicated a decelerated increase in the ascending limb of the scotopic (rod-sensitive) b-wave as well as a delayed return to baseline. These results suggest that PKC¦Į is an important modulator that affects bipolar cell signal transduction and termination. Confocal microscopy of retinal sections showed that PKC¦Į co-localized with calbindin, which indicates a PKC¦Į localization in close proximity to the horizontal cell terminals. In addition, the implicit time of the ERG c-alpha originating from the retinal pigment epitheli uM (RPE) and the recovery of photoreceptors from bleaching conditions were substantially faster in the knockout mice than in the wild-type control animals”£hese results suggest that PKC¦Į is a modulator of rod-bipolar cell function by accelerating glutamate-driven signal transduction and termination[19]
Ref 1Curr Top Med Chem. 2009;9(7):640-54.Small molecule inhibitors of PKCTheta as potential antiinflammatory therapeutics. To Reference
Ref 2J Clin Invest. 2008 Sep;118(9):3151-9.The PKC inhibitor AEB071 may be a therapeutic option for psoriasis. To Reference
Ref 3Bioorg. Med. Chem. Lett. 2(3):239-244 (1992) To Reference
Ref 4Bioorg Med Chem Lett. 2009 Feb 1;19(3):724-6. Epub 2008 Dec 11.(-)-Cercosporamide derivatives as novel antihyperglycemic agents. To Reference
Ref 5J Med Chem. 2000 Apr 6;43(7):1413-7.Inhibition of protein kinase C(alpha) by dequalinium analogues: dependence on linker length and geometry. To Reference
Ref 6J Nat Prod. 1998 Nov;61(11):1410-2.Phenylethanoid glycosides from Digitalis purpurea and Penstemon linarioides with PKCalpha-inhibitory activity. To Reference
Ref 7Bioorg Med Chem Lett. 2002 Jan 21;12(2):147-50.Mixed lineage kinase activity of indolocarbazole analogues. To Reference
Ref 8Bioorg. Med. Chem. Lett. 4(11):1303-1308 (1994) To Reference
Ref 9Bioorg Med Chem Lett. 1999 Aug 2;9(15):2279-82.Novel protein kinase C inhibitors: synthesis and PKC inhibition of beta-substituted polythiophene derivatives. To Reference
Ref 10Biochem J. 2000 Oct 1;351(Pt 1):95-105.Specificity and mechanism of action of some commonly used protein kinase inhibitors. To Reference
Ref 11J Med Chem. 1992 Jan;35(1):177-84.Inhibitors of protein kinase C. 1. 2,3-Bisarylmaleimides. To Reference
Ref 12J 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. To Reference
Ref 13Bioorg. Med. Chem. Lett. 5(18):2093-2096 (1995) To Reference
Ref 14Bioorg. Med. Chem. Lett. 5(18):2155-2160 (1995) To Reference
Ref 15Bioorg Med Chem Lett. 2004 Oct 18;14(20):5171-4.Synthesis of anilino-monoindolylmaleimides as potent and selective PKCbeta inhibitors. To Reference
Ref 16J 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. To Reference
Ref 17J Med Chem. 2009 Jul 9;52(13):3969-81.Design, synthesis, and biological activity of isophthalic acid derivatives targeted to the C1 domain of protein kinase C. To Reference
Ref 18Int J Oncol. 1998 Jun;12(6):1349-54. Protein kinase C and its isoforms in human breast cancer cells: relationship to the invasive phenotype. To Reference
Ref 19Invest Ophthalmol Vis Sci. 2010 Nov;51(11):6051-8. Epub 2010 Jun 16.PKC{alpha} is essential for the proper activation and termination of rod bipolar cell response. To Reference


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