PKC Inhibitor Specificity

Prod No.	Ref No.	Product Description	PKA	PKC	PKG	CAM Kinase	MLCK	Casein Kinase	PTK	Notes & MAPK, CDK & Other Protein Kinases
A-165	1-5	Adenosine 3',5'-cyclic- Monophosphothioate, RP-Isomer	11 uM
A7410	6	Amiloride HCl							EGFR
A3145	7-9	Apigenin		10 uM					FGFR(20uM)
A8186	10	Arg-Lys-Arg- Ala-Arg-Lys-GLu	350- 460 uM		85- 100 uM
A4308	11	Autocamtide 2-Related Inhibitory Peptide				CAMKII (40nM)
B6292	12	Bisindolylmaleimide I Hydrochloride (GF 109203X)	2.0 uM	14 nM
B-178	13-15	Butein	>500 uM	>500 uM					See Notes	EGFR(16uM); p60c-src (65uM)
P1431	18-19	Calmodulin								GRK 2&3 (2uM) GRK5 (40nM) & GRK6
C6303	20-21	Calphostin C	>50 uM	50 nM					>50uM
C2932	23	Chelerythrine chloride		0.66 uM
C-240	24	Rp-8- [(4Chlorophenyl)thio]- cGMPS Triethylamine			0.5 uM
D7802	25	Daidzein						CKII		Does not inhibit MAP2Kinase
D3768	27	Dequalinium Chloride		8- 15 uM						ß 1 (8-15uM), I,II,III (11uM)
D1916	29	5,6- Dichlorobenzimidazole riboside						CKII (4-10uM)
D4681	30-32	L-threo-Dihydrosphingosine		X
D2667	33,34	2,5-Dihydroxycinnamic Acid Methyl Ester							EGFR
E2250	36	Ellagic Acid	2uM	8 uM
E7881	37-39	Emodin	>200 uM	>200 uM				CKII (2uM)
E3645	40	rac-2-Ethoxy-3- Hexadecanamido-1- Propyl Phosphocholine		X						ID50=2.32uM for Leukemic HL60 cells
E3770	40	rac-2-Ethoxy-3- Octadecanamido-1- Propyl Phosphocholine		X						ID50= 1.64uM for Leukemic HL60 cells
G3381	41-43	Geldanamycin							erbB, EGFR, v-src
G6649/ G6776	44-50	Genistein	>100 uM	15 uM					See Notes	EGFR(2.6uM) insulin(41uM) V-src(26uM) V-abl(39uM)
G0897	51	Genistin							Neg. Control
G2911	12	GF 109203X (Bisindolylmaleimide I Hydrochloride)	2.0 uM	10 nM
I7016	52,53	H-7 Dihydrochloride (1-(5-Isoquinolinesulfonyl)- 2-methylpiperazine Dihydrochloride)	3.0 uM	6.0 uM	5.8 uM		97 uM	CKI (100uM) KII (780uM)
I6891	52,53	H-7 Free Base (1-(5-Isoquinolinesulfonyl) -2-methylpiperazine)	3.0 uM	6.0 uM	5.8 uM		97 uM	CKI (100uM) CKII (780uM)
M9656	52	H-8, N-(2-[Methylamino]ethyl)- 5-isoquinolinesulfonamide Hydrochloride	1.2 uM	14.4 uM	0.48 uM		68 uM	CKI (133uM) CKII (950uM)
B1427	54-57	H-89	48 nM	14 uM	340 nM	CAMKII (11uM)	39 uM	CKI (34uM), CKII (124uM)
I1392	59	HA 100	8uM	12 uM	4uM		240 uM
G1274	59-65	HA 1004	2.3 uM	40 uM	1.3 uM	CAMKII (13uM)	150 uM
H-139	66	HA-1077 2HCL	1.6 uM		1.6 uM		36 uM
H6649	67-69	Herbimycin A							p210bcr-abl
H5257	71	Hispidin		X
H7904	72	Hydroxytamoxifen		88 uM
H9252	73,74	Hypericin	>50 uM	3.3 uM
I0404	75	Indirubin 3'-monoxime								Glycogen synthase Kinase (5-50nM)& CDK (5-100nM)
I2142	76-82	KN-62	>100 uM	>100 uM		CAMKII (0.3- 1.8uM)	>100 uM
K-112	81-86	KN-92				Neg. Control
K1385	83	KN-93
K3761	87	KT5720	60 nM		2.4 nM
L2400	88-91	Lavendustin A							EGFR=4.4ng/ml
L5025	92	Leflunomide							BTK
M2272	93,94	Melittin		1-4 uM			0.08- 1.4 uM
M7795	40	rac-2-Methoxy-3- Hexadecanamido-1- Propyl phosphocholine		X
M8045	40	rac-2-Methoxy-3- Octadecanamido -1-Propyl phosphocholine		X
I2764	95-97	ML-7	21 uM	42 uM			300 nM
C1172	97-103	ML-9				X	X
M6760	104-105	Myricetin	27.5 uM	12.1 uM			1.7 uM	CKI (9uM), CKII (0.6uM)	pp130fps (1.8uM), insulin receptor(2.6)
N-161	106	NPC-15437 DiHCl		X
O0886	107	Olomoucine								CDK Inhibitor
P4509	108-109	Palmitoyl-DL-Carnitine Chloride		34 uM
P-215	110-112	PD 098,059								prevents the activation of MAPKK1 by Raf or MEK kinase
P7912	113	Phloretin		~5 uM
P0453	114-118	Piceatannol	3 uM	8uM			12 uM		See notes	Tyrosine kinases Syk, p40(15uM), p56lck(66uM) and p72. CDK(19uM)
P1004	119	Polymyxin B Sulfate		~10 uM
P6062	120	Protein kinase A inhibitor fragment 6-22 amide	1.6 nM
P8462	121	Protein Kinase C Fragment 19-36	423 uM	147 nM			24 uM
P0393	122-125	Protein Kinase Inhibitor from porcine heart	X
P0300	123-125	Protein Kinase Inhibitor Rabbit Sequence	2.3 nM
P5015	123-125	Protein Kinase Inhibitor from rabbit muscle	X
Q0125	105,126, 127	Quercetin		20- 40 uM				CKG (220nM), CKI (45uM), CKII (100nM)	See Notes	EGF Receptor (410nM), I, IIA, IIB(10uM), III(10uM), Mg++ Dep., P60v-src (50uM)
R2146	128-133	Radicicol							src(0.1ug/ml)
R0395	134-135	Rapamycin							p70s6k, p33cdk2 and p34cdc2.	mTOR
R-136	136-139	Ro 31-8220 (Bisindolylmaleimide IX)	1.5 uM	7.6 nM		CAMKII (17uM)				GRK5, GSK3
R-137	136,140, 141	Ro 32-0432								showed a 10-fold selectivity for PKC- aand a 4-fold selectivity for PKC-ß I over PKC-epsilon. GRK-5 inhibitor; less potent inhibitor of GRK-2 or GRK-3
R7772	142,143	Roscovitine								p34cdc2 (0.45uM), CDK2
R5648	144	Rottlerin		See notes		CAMKIII (5.3uM)				PKCdelta 3-6 5M; PKCa , PKCß, PKCgamma 30-42 5M
S8307	145	SB 203580								p38 MAPK (0.5uM)
S7049	146-148	D-Sphingosine		53 uM		CAMKIII (20uM)				Also Inhibits MAPK
S4400	73,105, 149-155	Staurosporine	6 nM	2.7- 5.5 nM	8.5 nM	CAMKII (20nM)	21 nM		C-src(10nM), EGFR(600nM), Insulin(60nM)V- Src(6nM)V- abl(80nM)	Inhibits CDK 1,2&5
T5648	157,158	Tamoxifen Free Base		5- 15 uM
T9262	157,158	Tamoxifen Citrate		5 uM
T3126	160	(+)-a-Tocopherol Acid Succinate		X
T7254	105	N a-p-Tosyl-L-lysine chloromethyl ketone Hydrochloride		1 mM
T7040	161	Tyrphostin 1							EGFR >1250uM	Negative Control
T7165	161	Tyrphostin 23							EGFR 35uM
T7665	161	Tyrphostin 51							EGFR 0.8uM
T7790	161	Tyrphostin 63							EGFR 6500uM	Negative Control
T-182	162,163	Tyrphostin A9							PDGFR(0.5uM), EGFR(460uM)
T9177	164	Tyrphostin AG 126							X	Blocks TNF-a and NO production in macrophages
T3434	51,165, 166	Tyrphostin AG 490							Jak-2
T2067	167	Tyrphostin AG 879							pp140c-trk(10uM)
T4057	168	Tyrphostin AG 1296							PDGFR
T5317	161	Tyrphostin AG 1433							PDGR & VEGFR	PDGF ß receptor (5 uM); VEGFreceptor (9.3uM)
T4182	169	Tyrphostin AG 1478							EGFR
T4192	161	Tyrphostin SU 1498							VEGFR(700 Nm)
U-120	170-172	U0126								MEK1(72nM), MEK2(58nM)
W1628	173,174	Wortmannin					200 nM			PI3Kinase (3nM)

No.	References
1	Rothermel, J.D., et al., A mechanistic and kinetic analysis of the interactions of the diastereoisomers of adenosine 3',5'-(cyclic)phosphorothioate with purified cyclic AMP-dependent protein kinase, Biochem. J., 251, 757 (1988).
2	Parker Botelho, L.H., et al., cAMP analog antagonists of cAMP action, Methods Enzymol., 159, 159-172 (1988).
3	Richter-Landsberg, C., Jastorff, B., In vitro phosphorylation of microtubule-associated protein 2: Differential effects of cyclic AMP analogues, J. Neurochem., 45, 1218-1222 (1985).
4	Dostmann, W.R.G., et al., Probing the cyclic nucleotide binding sites of cAMP-dependent protein kinases I and II with analogs of adenosine 3',5'-cyclic phosphorothioates, J. Biol. Chem., 265, 10484 (1990).
5	Yokozaki, H., et al., Unhydrolyzable analogues of adenosine 3':5'-monophosphate demonstrating growth inhibition and differentiation in human cancer cells, Cancer Res., 52, 2504 (1992).
6	Davis, R.J., Czech, M.P., Amiloride directly inhibits growth factor receptor tyrosine kinase activity, J. Biol. Chem., 260, 2543-51 (1985)
7	Huang, Y.T., et al., Inhibitions of protein kinase C and proto-oncogene expressions in NIH 3T3 cells by apigenin, Eur. J. Cancer, 32, 146-151 1996).
8	Kuo ML, Yang NC, Reversion of v-H-ras-transformed NIH 3T3 cells by apigenin through inhibiting mitogen activated protein kinase and its downstream oncogenes.Biochem. Biophys. Res. Commun., 212, 767-75 (1995)
9	Yin F.M, Signal pathways involved in apigenin inhibition of growth and induction of apoptosis of human anaplastic thyroid cancer cells. Anticancer Res., 19, 4297-303 (1999)
10	Glass, D., et al., Differential and common recognition of the catalytic sites of the cGMP-dependent and cAMP-dependent protein kinases by inhibitory peptides derived from the heat-stable inhibitor protein, Biochem. J., 213, 159 (1983)
11	Ishida, A., et al., A novel highly specific and potent inhibitor of calmodulin-dependent protein kinase II., Biochem. Biophys. Res. Commun., 212, 806-12 (1995)
12	Toullec, D., et al., The isindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C., J. Biol. Chem., 266, 15771 (1991).
13	Yang, E., et al., Butein, a specific protein tyrosine kinase inhibitor, Biochem. Biophys. Res. Commun., 245, 435-438 (1998).
14	Yu, S.M., et al., Endothelium- dependent relaxation of rat aorta by butein, a novel cyclic AMP-specific phosphodiesterase inhibitor, Eur. J. Pharmacol., 280, 69-77 (1995).
15	Aizu, E., et al., Inhibition of 12-O-tetradecanoylphorbol-13-acetate-mediated epidermal ornithine decarboxylase induction and skin tumor promotion by new lipoxygenase inhibitors lacking protein kinase C inhibitory effects, Carcinogenesis, 7, 1809-1812 (1986).
16	Kitagawa, M., et al., Butyrolactone I, a selective inhibitor of cdk2 and cdc2 kinase., Oncogene, 8, 2425-32 (1993)
17	Okuyama, A., et al., [CDK and MMP inhibitors]., Gan To Kagaku Ryoho, 24, 1547-62 (1997)
18	Chuang, T.T., et al., Inhibition of G protein-coupled receptor kinase subtypes by Ca2+/calmodulin., J. Biol. Chem., 271, 28691-6 (1996)
19	Pitcher, J. A., Freedman, N. J. and Lefkowitz, R. J., G protein-coupled receptor kinases., Ann. Rev. Biochem,. 67, 653-92 (1998).
20	Tamaoki, T. and Nakano, H., Potent and specific inhibitors of protein kinase C of microbial origin, Biotechnology (NY), 8, 732-735 (1990).
21	Kobayashi, E., et al., Calphostin C (UCN-1028C), a novel microbial compound, is a highly potent and specific inhibitor of protein kinase C. Biochem. Biophys. Res. Commun., 159, 548-553 (1989).
22	Smith, et al., Functional determinants in the autoinhibitory domain of calcium/calmodulin-dependent protein kinase II. J. Biol. Chem., 267, 1761-1768 (1992)
23	Herbert, J.M., et al., Chelerythrine is a potent and specific inhibitor of protein kinase C. Biochem. Biophys. Res. Commun., 172, 993-999 (1990).
24	Butt, E., (Rp)-8-pCPT-cGMPS, a novel cGMP-dependent protein kinase inhibitor., Eur J Pharmacol., 269, 265-8 (1994)
25	Higashi, K. and Ogawara, H., Daidzein inhibits insulin- or insulin-like growth factor-1-mediated signaling in cell cycle progression of Swiss 3T3 cells., Biochim. Biophys. Acta., 1221, 29-35 (1994)
26	Faltyrek, C.R., et al., Damnacanthal is a highly potent, selective inhibitor of p56lck tyrosine kinase activity. Biochemistry, 34, 12404 (1995).
27	Rotenberg, S.A., Inhibition of rodent protein kinase C by the anticarcinoma agent dequalinium., Cancer Res., 50, 677-85 (1990)
28	Yen, A., Scoong, S., Retinoic acid-induced RB (retinoblastoma) hypophosphorylation enhanced by CGP 52411 (4,5-dianilinophthalimide), an EGF family tyrosine kinase receptor inhibitor. Eur. J. Cell Biol., 69, 327-334 (1996).
29	Zandomeni, R., et al., Casein kinase type II is involved in the inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole of specific RNA polymerase II transcription, J. Biol. Chem., 261, 3414-9 (1986)
30	Schwartz, G.K., et al., A pilot clinical/pharmacological study of the protein kinase C-specific inhibitor safingol alone and in combination with doxorubicin., Clin. Cancer Res., 3, 537-43 (1997).
31	Schwartz, G.K., et al., Potentiation of apoptosis by treatment with the protein kinase C-specific inhibitor safingol in mitomycin C-treated gastric cancer cells., J. Natl. Cancer Inst., 87, 1394-9 (1995)
32	Sachs, C.W., et al., Partial inhibition of multidrug resistance by safingol is independent of modulation of P-glycoprotein substrate activities and correlated with inhibition of protein kinase C., J. Biol. Chem., 270, 26639-48 (1995)
33	Geltz, et al., The p85 and p110 subunits of phosphatidylinositol 3-kinase-alpha are substrates, in vitro, for a constitutively associated protein tyrosine kinase in platelets. Blood, 91, 930-939 (1998).
34	Haier, et al., Influence of phosphotyrosine kinase inhibitors on adhesive properties of highly and poorly metastatic HT-29 colon carcinoma cells to collagen. Int. J. Colorectal. Dis., 14, 119-127 (1999).
35	Basson, et al., Effects of modulation of tyrosine phosphorylation on brush border enzyme activity in human Caco-2 intestinal epithelial cells. Cell. Tissue Res., 292, 553-562 (1998).
36	Wang, B.H., et al., Inhibition of eukaryote serine/threonine-specific protein kinases by piceatannol., Planta Med., 64, 195-9 (1998)
37	Yim, et al., Emodin, an anthraquinone derivative isolated from the rhizomes of Rheum palmatum, selectively inhibits the activity of casein kinase II as a competitive inhibitor. Planta Med., 65, 9-13 (1999).
38	Kumar, et al., Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) inhibits TNF-induced NF-kappaB activation, IkappaB degradation, and expression of cell surface adhesion proteins in human vascular endothelial cells. Oncogene, 17, 913-918 (1998).
39	Zhang, et al., Tyrosine kinase inhibitor emodin suppresses growth of HER-2/neu-overexpressing breast cancer cells in athymic mice and sensitizes these cells to the inhibitory effect of paclitaxel. Clin. Cancer Res., 5, 343-353 (1999).
40	Marx, M.H., et al., Synthesis and evaluation of neoplastic cell growth inhibition of 1-N-alkylamide analogues of glycero-3-phosphocholine., J. Med. Chem., 31, 858 (1988)
41	Whitesell, L., et al., Stable and specific binding of heat shock protein 90 by geldanamycin disrupts glucocorticoid receptor function in intact cells. Mol. Endocrinol., 10, 705-712 (1996).
42	Supko, J.G., et al., Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent. Cancer Chemother. Pharmacol., 36, 305-315 (1995).
43	Chavany, C., et al., p185erbB2 binds to GRP94 in vivo. Dissociation of the p185erbB2/GRP94 heterocomplex by benzoquinone ansamycins precedes depletion of p185erbB2. J. Biol. Chem., 271, 4974-4947 (1996).
44	Geissler, J.F., Thiazolidine-diones. Biochemical and biological activity of a novel class of tyrosine protein kinase inhibitors., J. Biol. Chem., 265, 22255-61 (1990)
45	Akiyama, T., et al., Genistein, a specific inhibitor of tyrosine-specific protein kinases. J. Biol. Chem., 262, 5592-5595 (1987).
46	Koroma, B.M. and de Juan, E., Inhibition of protein tyrosine phosphorylation in endothelial cells: relationship to antiproliferative action of genistein., Biochem. Soc. Trans., 25, 35-40 (1997)
47	O'Dell, T.J., et al., Long-term potentiation in the hippocampus is blocked by tyrosine kinase inhibitors. Nature, 353, 558-560 (1991).
48	Huang J., et al., Genistein inhibits protein Histidine kinase. J. Biol. Chem., 267, 15511-15515 (1992).
49	Hakansson, G., and Allen, J.F., Histidine and tyrosine phosphorylation in pea mitochondria: evidence for protein phosphorylation in respiratory redox signalling. FEBS Lett., 372, 238-242 (1995).
50	Igarashi, M., and Komiya, Y., Tyrosine phosphorylation and immunodetection of vinculin in growth cone particle (GCP) fraction and in CP-cytoskeletal Subfractions.J. Neurosci. Res., 30, 266-274 (1991).
51	Potier, et al., Protein tyrosine kinase inhibitors reduce high-activating calcium currents in CA1 pyramidal neurones from rat hippocampal slices. Brain Res., 816, 587-597 (1999).
52	Bradshaw, D., et al, Therapeutic potential of protein kinase C inhibitors., Agents Actions 1993 Jan;38(1-2):135-47
53	Hidaka, H., et al., Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry, 23, 5036-5041 (1984).
54	Chijiwa, T., et al., J. Biol. Chem., 265, 5267 (1990)
55	Hidaka, et al., The Biology and Medicine of Signal Transduction, pp. 485-90, Nishizuka, Y., et al., eds, Raven Press NY (1990)
56	Murol, M. and Suzuki, T., Cell Signal., 5, 289 (1993)
57	Fujihara, M., et al., J. Biol. Chem., 268, 14898 (1993)
58	Inagaki, et al., N-(2-Aminoethyl)-5-isoquinolinesulfonamide, a newly synthesized protein kinase inhibitor, functions as a ligand in affinity chromatography. J. Biol. Chem., 260, 2922(1985).
59	Hagiwara, M., et al., Selective modulation of calcium-dependent myosin phosphorylation by novel protein kinase inhibitors, isoquinolinesulfonamide derivatives., Mol Pharmacol., 32, 7-12 (1987)
60	Xiao, G.H., et al., cAMP-dependent negative regulation of rat aldehyde dehydrogenase class 3 gene expression. J. Biol. Chem., 272, 3238-3245 (1997).
61	Luo, S.F., et al., Effect of forskolin on bradykinin-induced calcium mobilization in cultured canine tracheal smooth muscle cells. Cell Signal., 9, 159-167 (1997).
62	Svenningsen, A.F. and Kanje, M., Regulation of Schwann cell proliferation in cultured segments of the adult rat sciatic nerve. J. Neurosci. Res., 52, 530-537 (1998).
63	Crowley, M.R., et al., HA1004, an intracellular calcium antagonist, selectively attenuates pulmonary hypertension in newborn lambs. J. Cardiovasc. Pharmacol., 23, 806-813 (1994).
64	Leahy, J.C. and Vallano, M.L., Differential effects of isoquinolinesulfonamide protein kinase inhibitors on CA1 responses in hippocampal slices. Neuroscience, 44, 361-370 (1991).
65	Tsushima, H., et al., Human erythropoietin receptor increases GATA-2 and Bcl-xL by a protein kinase C-dependent pathway in human erythropoietin-dependent cell line AS-E2. Cell Growth Differ., 8, 1317-1328 (1997).
66	Asano, T., et al., Vasodilator actions of HA1077 in vitro and in vivo putatively mediated by the inhibition of protein kinase., Br J Pharmacol., 98, 1091-100 (1989)
67	Fukazawa, H., et al., Specific inhibition of cytoplasmic protein tyrosine kinases by herbimycin A in vitro., Biochem. Pharmacol., 42, 1661-71(1991)
68	Zakar, et al., Tyrosine kinase inhibitors block the glucocorticoid stimulation of prostaglandin endoperoxide H synthase expression in amnion cells. Can. J. Physiol. Pharmacol., 77, 138-142 (1999).
69	Davis, et al., Herbimycin A and geldanamycin inhibit okadaic acid-induced apoptosis and p38 activation in NRK-52E renal epithelial cells. Toxicol. Appl. Pharmacol., 16, 59-74 (1999).
70	Uberall, F., et al., Hexadecylphosphocholine inhibits inositol phosphate formation and protein kinase C activity., Cancer Res., 51, 807-12 (1991)
71	Gonindard, C., et al., Synthetic hispidin, a PKC inhibitor, is more cytotoxic toward cancer cells than normal cells in vitro., Cell Biol. Toxicol., 13, 141-53 (1997)
72	Eyster, K.M., Nonsteroidal antiestrogen inhibition of protein kinase C in human corpus luteum and placenta., Biochem. Pharmacol., 38, 3497-503 (1989)
73	Tamaoki, T., et al., The Biology and Medicine of Signal Transduction, pp. 497-501, Nishizuka, Y., et al., eds, Raven Press NY (1990)
74	Takahashi, I., et al., Hypericin and pseudohypericin specifically inhibit protein kinase C: possible relation to their antiretroviral activity. Biochem. Biophys. Res. Commun., 165, 1207-1212 (1989).
75	Leclerc, S., Indirubins Inhibit Glycogen Synthase Kinase-3beta and CDK5/P25, Two Protein Kinases Involved in Abnormal Tau Phosphorylation in Alzheimer's Disease., J. Biol. Chem., 276, 251-260 (2001)
76	Minami, H., The effect of KN-62, Ca2+/calmodulin dependent protein kinase II inhibitor on cell cycle., Biochem. Biophys. Res. Commun., 199, 241-8 (1994)
77	MacLeod, et al., Ca(2+)/Calmodulin kinase II and decreases in intracellular pH are required to activate K(+) channels after substantial swelling in villus epithelial cells. J. Membr. Biol., 172, 59-66 (1999).
78	Fan, et al., Inhibition of calcium/calmodulin-dependent protein kinase II in rat hippocampus attenuates morphine tolerance and dependence. Mol. Pharmacol., 56, 39-45 (1999).
79	Communi, et al., Calcium-calmodulin-dependent protein kinase II and protein kinase C-mediated phosphorylation and activation of D-myo-inositol 1,4, 5-trisphosphate 3-kinase B in astrocytes. J. Biol. Chem., 274, 14734-14742 (1999).
80	Fan, et al., Inhibition of calcium/calmodulin-dependent protein kinase II in rat hippocampus attenuates morphine tolerance and dependence. Mol. Pharmacol., 56, 39-45 (1999).
81	Sumi, M., et al., The newly synthesized selective Ca2+/calmodulin dependent protein kinase II inhibitor KN-93 reduces dopamine contents in PC12h cells., Biochem. Biophys. Res. Commun., 181, 968-75 (1991)
82	Tokumitsu, H., et al., KN-62, 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine, a specific inhibitor of 2+/calmodulin-dependent protein kinase II. J. Biol. Chem., 265, 4315-20 (1990)
83	Tessier, et al., Regulation of the transient outward K(+) current by Ca(2+)/Calmodulin-dependent protein kinases II in human atrial myocytes. Circ. Res., 85, 810-819 (1999).
84	Tombes, R.M., et al., G1 cell cycle arrest and apoptosis are induced in NIH 3T3 cells by KN-93, an inhibitor of CaMK-II (the multifunctional Ca2+/CaM kinase)., Cell Growth Differ., 6, 1063-70 (1995)
85	Smith, et al., Increased calcium/calmodulin protein kinase activity in astrocytes chronically exposed to ethanol: influences on glutamate transport.Neurosci. Lett., 269, 145-148 (1999).
86	Wasmeier, et al., Secretagogue-dependent phosphorylation of phogrin, an insulin granule membrane protein tyrosine phosphatase homologue. Biochem. J., 341, 563-569 (1999).
87	Kase, H., K-252 compounds, novel and potent inhibitors of protein kinase C and cyclic nucleotide-dependent protein kinases., Biochem Biophys. Res. Commun., 142, 436-40 (1987)
88	Hsu, C.Y., et al, Kinetic analysis of the inhibition of the epidermal growth factor receptor tyrosine kinase by Lavendustin-A and its analogue. J. Biol. Chem., 266, 21105-12 (1991)
89	Onoda, T., Isolation of a novel tyrosine kinase inhibitor, lavendustin A, from Streptomyces griseolavendus., J. Nat. Prod., 52, 1252-7 (1989)
90	Huang, et al., Protein tyrosine kinase is required for the induction of long-term potentiation in the rat hippocampus. J. Physiol. (Lond), 520, 783-796 (1999).
91	Taskinen, et al., Inhibition of atrial wall stretch-induced cardiac hormone secretion by lavendustin A, a potent tyrosine kinase inhibitor. Endocrinology, 140, 4198-4207 (1999).
92	Mahajan, S., et al., Rational design and synthesis of a novel anti-leukemic agent targeting Bruton's tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta-hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide]., J. Biol. Chem., 274, 9587-99 (1999)
93	Katoh, N., et al., Inhibition by melittin of phospholipid-sensitive and calmodulin-sensitive Ca2+-dependent protein kinases. Biochem. J., 202, 217-24 (1982)
94	Raynor, R.L., et al., Membrane interactions of amphiphilic polypeptides mastoparan, melittin, polymyxin B, and cardiotoxin. Differential inhibition of protein kinase C, Ca2+/calmodulin-dependent protein kinase II and synaptosomal membrane Na,K-ATPase, and Na+ pump and differentiation of HL60 cells., J. Biol. Chem., 266, 2753 (1991)
95	Krarup. T., et al., Na+-K+-2Cl- cotransport in Ehrlich cells: regulation by protein phosphatases and kinases. Am. J. Physiol., 275, 239-50 (1998)
96	Makishima, M., et al., Induction of differentiation of human leukemia cells by inhibitors of myosin light chain kinase., FEBS Lett., 287, 175 (1991).
97	Saitoh, M., et al., Selective inhibition of catalytic activity of smooth muscle myosin light chain kinase. J. Biol. Chem., 262, 7796-7801 (1987)
98	Saitoh, M., et al., The modulatory role of myosin light chain phosphorylation in human platelet activation., Biochem. Biophys. Res. Commun., 140, 280-7 (1986)
99	Hidaka, H., Properties and use of H-series compounds as protein kinase inhibitors., Methods Enzymo., 201, 328-39 (1991)
100	Ito, M., et al., Inhibition of natural killer cell-mediated cytotoxicity by ML-9, a selective inhibitor of myosin light chain kinase. Int. J. Immunopharmacol., 11, 185-190 (1989).
101	Inoue, G., et al., Effects of ML-9 on insulin stimulation of glucose transport in 3T3-L1adipocytes. J. Biol. Chem., 268, 5272-5278 (1993).
102	Nagatsu, T., Effects of myosin light-chain kinase inhibitor on catecholamine secretion from rat pheochromocytoma PC12h cells. Biochem. Biophys. Res. Commun., 143, 1045-8 (1987)
103	Reig, J.A., et al, Naphthalenesulfonamide derivatives ML9 and W7 inhibit catecholamine secretion in intact and permeabilized chromaffin cells. Neurochem. Res., 18, 317-323 (1993).
104	Hagiwara, M., et al., Differential effects of flavonoids as inhibitors of tyrosine protein kinases and serine/threonine protein kinases. Biochem Pharmacol., 37, 2987-92 (1988)
105	Handbook of Enzyme Inhibitors, H. Zollner (1993)
106	Sullivan, et al., 2,6-Diamino-N-([1-(1-oxotridecyl)-2-piperidinyl]-methyl)hexanamide (NPC 15437): A selective inhibitor of protein kinase C. Agents Actions, 34, 138-141 (1991).
107	Vesely, J., et al., Inhibition of cyclin-dependent kinases by purine analogues. Eur. J. Biochem., 224, 771-786 (1994).
108	Nakadate, T., and Blumberg, P.M., Modulation by palmitoylcarnitine of protein kinase C activation. Cancer Res., 47, 6537-6542 (1987)
109	Robinson, P.J., et al., MDL 27,032 [4-propyl-5-(4-pyridinyl)-2(3H)-oxazolone], an active site-directed inhibitor of protein kinase C and cyclic AMP-dependent protein kinase that relaxes vascular smooth muscle., J. Pharmacol. Exp. Ther., 255, 1392-8 (1990)
110	Alessi, et al., PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. J. Biol. Chem., 270, 27489-27494 (1995).
111	Dudley, et al., A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc. Natl. Acad. Sci. USA, 95, 7686-7689 (1995)
112	Pang, et al., Inhibition of MAP kinase blocks the differentiation of PC-12 cells induced by nerve growth factor. J. Biol. Chem., 270, 13585-13588 (1995).
113	Grosman, N., Inhibitory effect of phloretin on histamine release from isolated rat mast cells., Agents Actions, 25, 284-90 (1988)
114	Wang, B.H., Panta Med., 64, 195 (1998)
115	Cambien, et al., Src-regulated extracellular signal-related kinase and syk-regulated c-Jun N-terminal kinase pathways act in conjunction to induce IL-1 synthesis in response to microtubule disruption in HL60 cells. J. Immunol., 163, 5079-85 (1999).
116	Geahlen, R.L., Piceatannol (3,4,3',5'-tetrahydroxy-trans-stilbene) is a naturally occurring protein-tyrosine kinase inhibitor.Biochem. Biophys. Res. Commun., 165, 241-5 (1989)
117	Tkaczyk, et al., Fc epsilon RI-mediated antigen endocytosis turns interferon-gamma-treated mouse mast cells from inefficient into potent antigen-presenting cells. Immunology, 97, 333-340 (1999).
118	Zheng, et al., Piceatannol, a stilbene phytochemical, inhibits mitochondrial F0F1-ATPase activity by targeting the F1 complex. Biochem. Biophys. Res. Commun., 261, 499-503 (1999).
119	Nel, A.E., Polymyxin B causes coordinate inhibition of phorbol ester-induced C-kinase activity and proliferation of B lymphocytes., Biochem. Biophys. Res. Commun., 128, 1364-72 (1985)
120	Glass, D.B., et al., Protein kinase inhibitor-(6-22)-amide peptide analogs with standard and nonstandard amino acid substitutions for phenylalanine 10. Inhibition of cAMP-dependent protein kinase., J. Biol. Chem., 264, 14579 (1989).
121	House, C. and Kemp, B.E., Protein Kinase C contains a pseudosubstrate protope in its regulatory domain., Science, 238, 1726 (1987)
122	Brostrom, C.O. and Kon, C., An improved protein binding assay for cyclic AMP. Anal. Biochem., 58, 459 [1974].
123	Walsh, D.A., et al., Krebs EG: Purification and characterization of a protein inhibitor of adenosine 3',5'-monophosphate-dependent protein kinases. J. Biol. Chem., 246, 1977 (1971).
124	Cheng, H.C., A potent synthetic peptide inhibitor of the cAMP-dependent protein kinase., J. Biol. Chem., 261, 989-92(1986)
125	Van Patten, S.M., et al.,The inhibitor protein of the cAMP-dependent protein kinase-catalytic subunit interaction. Parameters of complex formation., J. Biol. Chem., 261, 5514-23 (1986)
126	Baginski, I., Selective inhibition of tyrosine protein kinase by a synthetic multisubstrate analog., Biochem. Biophys. Res. Commun., 165, 1324-30 (1989)
127	Glossmann, H., at al., Quercetin inhibits tyrosine phosphorylation by the cyclic nucleotide-independent, transforming protein kinase, pp60src. Naunyn Schmiedebergs Arch. Pharmacol., 317, 100-2 (1981)
128	Kwon, H.J., et al., Potent and specific inhibition of p60v-src protein kinase both in vivo and in vitro by radicicol., Cancer Res., 52, 6926-30 (1992)
129	Oikawa, T., et al., Radicicol, a microbial cell differentiation modulator, inhibits in vivo angiogenesis. Eur. J. Pharmacol., 241, 221-227 (1993).
130	Zhao, J.F., et al., Suppression of RAS and MOS transformation by radicicol. Oncogene, 11, 161-173 (1995).
131	Pillay, I., et al., Radicicol inhibits tyrosine phosphorylation of the mitotic Src substrate Sam68 and retards subsequent exit from mitosis of Src-transformed cells. Cell Growth Differ., 7, 1487-1499 (1996).
132	Chanmugan, P., et al., Radicicol, a protein tyrosine kinase inhibitor, suppresses the expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide and in experimental glomerulonephritis. J. Biol. Chem., 270, 5418-5426 (1995).
133	Shimada, Y., et al., Induction of differentiation of HL-60 cells by the anti-fungal antibiotic, radicicol. J. Antibiot., 48, 824-830 (1995).
134	Price, D.J., et al. Rapamycin-induced inhibition of the 70-kilodalton S6, protein kinase. Science, 257, 973-977 (1992).
135	Morice, W.G., et al. Rapamycin inhibition of interleukin-2-dependent p33cdk2 and p34cdc2 kinase activation in T lymphocytes. J. Biol. Chem., 268, 22737-22745 (1993).
136	Moore, J.B., et al., Inhibition of PTH desensitization by inhibition of the G protein-coupled receptor kinase-5 enzyme with Ro 32-0432. FASEB J. Part II, 12, A741 (1998)
137	Beltman, J., et al., The selective protein kinase C inhibitor, Ro-31-8220, inhibits mitogen-activated protein kinase phosphatase-1 (MKP-1) expression, induces c-Jun expression, and activates J N-terminal kinase. J. Biol. Chem., 271, 27018-27024 (1996).
138	Alessi, D.R., The protein kinase C inhibitors Ro 318220 and GF 109203X are equally potent inhibitors of MAPKAP kinase -1beta (Rsk-2) and p70 S6 kinase. FEBS Lett., 402, 121-123 (1997)
139	Twomey, B., The effect of new potent selective inhibitors of protein kinase C on the neutrophil respiratory burst., Biochem. Biophys. Res. Commun., 171, 1087-92 (1990)
140	Wilkinson, S.E., et al., Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C. Biochem. J., 294, 335-337 (1993)
141	Gozal, D., et al., Cardiorespiratory responses to systemic administration of a protein kinase C inhibitor in conscious rats. J. Appl. Physiol., 84, 641-648 (1998).
142	Gray, N., et al., ATP-site directed inhibitors of cyclin-dependent kinases. Curr. Med. Chem., 6, 859-75 (1999)
143	DeAzevado, W.F., et al., Inhibition of cyclin-dependent kinases by purine analogues: crystal structure of human cdk2 complexed with roscovitine. Eur. J. Biochem., 243, 518-526 (1997).
144	Gschwendt, M., Rottlerin, a novel protein kinase inhibitor., Biochem. Biophys. Res. Commun., 199, 93-8 (1994)
145	Saklatvala, J., et al., Role for p38 mitogen-activated protein kinase in platelet aggregation caused by collagen or a thromboxane analogue., J. Biol. Chem., 271, 6586-9 (1996)
146	Jefferson, A.B., et al., Sphingosine inhibits calmodulin-dependent enzymes., J. Biol. Chem., 263, 15241-4 (1988)
147	Junco, M., et al., Substrate-dependent inhibition of protein kinase C by specific inhibitors,. FEBS Lett., 263, 169-71 (1990)
148	Sakakura et al., Selectivity of sphingosine-induced apoptosis. Lack of activity of DL-erythyro-dihydrosphingosine.Biochem. Biophys. Res. Commun., 246, 827-30 (1998).
149	Condrescu, et al., Mode-specific inhibition of sodium-calcium exchange during protein phosphatase blockade. J. Biol. Chem., 274, 33279-33286 (1999).
150	Sielecki, T.M., et al., Cyclin-dependent kinase inhibitors: useful targets in cell cycle regulation., J. Med. Chem., 43, 1-18 (2000)
151	Tamaoki, T., et al., Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase., Biochem. Biophys. Res. Commun., 135, 397-402 (1986)
152	Peet, et al., IkappaB kinases alpha and beta show a random sequential kinetic mechanism and are Inhibited by staurosporine and quercetin. J. Biol. Chem., 274, 32655-32661 (1999).
153	Wisniewski, et al., Assay for IkappaB kinases using an in vivo biotinylated IkappaB protein substrate. Anal. Biochem., 274, 220-228 (1999).
154	Droillard, M.J., et al., Identification of calreticulin-like protein as one of the phosphoproteins modulated in response to oligogalacturonides in tobacco cells. Planta, 202, 341-348 (1997).
155	Radloff, M., and Gercken, G., Protein kinase C activity and phosphoprotein pattern in stimulated alveolar macrophages.Toxicol. Lett., 88, 139-145 (1996).
156	Nekadate and Blumberg, Cancer Res., 47, 6547(1987) get Ki
157	da Rocha, A.B., et al., Tamoxifen inhibits particulate-associated protein kinase C activity, and sensitises cultured human glioblastoma cells not to etoposide but to gamma-radiation and BCNU., Eur. J. Cancer, 35, 833-9 (1999)
158	O'Brian, C.A., et al., Inhibition of protein kinase C by tamoxifen., Cancer Res., 45, 2462-5 (1985)
159	Singh, J., et al., Structure-based design of a potent, selective, and irreversible inhibitor of the catalytic domain of the erbB receptor subfamily of protein tyrosine kinases., J. Med. Chem., 40, 1130-5 (1997)
160	Chatelain, E., et al., Inhibition of smooth muscle cell proliferation and protein kinase C activity by tocopherols and tocotrienols., Biochim. Biophys. Acta., 1176, 83-9 (1993)
161	Supplier Information
162	Levitzki, A., Gilon, C., Tyrphostins as molecular tools and potential antiproliferative drugs. Trends Pharmacol. Sci., 12, 171-174 (1991).
163	Bilder, et al., Tyrphostins inhibit PDGF-induced DNA synthesis and associated early events in smooth muscle cells. Am. J. Physiol., 260, C721-C730 (1991).
164	Novogrodsky, A., et al., Science, 264, 1319 (1994)
165	Abe, et al., Fyn and JAK2 mediate Ras activation by reactive oxygen species. J. Biol. Chem., 274, 21003-21010 (1999).
166	Al-Shami, et al., granulocyte-macrophage colony-stimulating factor-activated signaling pathways in human neutrophils. Involvement of Jak2 in the stimulation of phosphatidylinositol 3-kinase. J. Biol. Chem., 274, 5333-5338 (1999).
167	Ohmichi, M., et al.,The tyrosine kinase inhibitor tyrphostin blocks the cellular actions of nerve growth factor., Biochemistry, 32, 4650-8 (1993)
168	Kovalenko, M., et al., Cancer Res., 54, 6106 (1994)
169	Osherov, N. and Levitzki, A., Eur. J. Biochem., 225, 1047 (1994).
170	Favata, M., et al., Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J. Biol. Chem., 273, 18623-18632 (1998).
171	DeSilva, D., et al, Inhibition of mitogen-activated protein kinase kinase blocks T cell proliferation but does not induce or prevent anergy. J. Immunol., 160, 4175-4181 (1998).
172	Duncia, J.V., et al., MEK inhibitors: The chemistry and biological activity of U0126, its analogs, and cyclization products. Bioorg. Med. Chem. Letts., 8, 2839-2844 (1998).
173	Nakanishi, S., et al., Wortmannin, a microbial product inhibitor of myosin light chain kinase. J. Biol. Chem., 267, 2157-2163 (1992).
174	Yano, H., et al., Biochemical and pharmacological studies with KT7692 and LY294002 on the role of phosphatidylinositol 3-kinase in Fc epsilon RI-mediated signal transduction. Biochem. J., 312, 145-50 (1995)

Selecting an appropriate protein kinase inhibitor can pose a challenge due to the complexity of the protein kinase family. Factors such as inhibitor specificity and cell permeability should be considered. The table below is based on currently available data. For specific information on specific inhibitors, consult the citations. Specific kinetic data for inhibitors marked with an "X" was not available. References may be viewed by clicking in the reference column or scrolling down past the product table.

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