Go6976

Manufactured by Bio-Techne

Sourced in United Kingdom, United States

Go6976 is a small molecule inhibitor that inhibits the activity of protein kinase C (PKC). It has a potent and selective inhibitory effect on PKC, particularly the alpha and beta isoforms. Go6976 is commonly used as a research tool to study the role of PKC in various cellular processes.

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Lab products found in correlation

Gf109203x, by Bio-Techne (5 mentions) Rottlerin, by Bio-Techne (3 mentions) Go6983, by Bio-Techne (3 mentions) Pd98059, by Bio-Techne (3 mentions) Daunorubicin, by Merck Group (2 mentions) Bio5192, by Bio-Techne (2 mentions) Cellevent caspase 3 7 green flow cytometry assay kit, by Thermo Fisher Scientific (2 mentions) Cytarabine, by Bio-Techne (2 mentions) Bms 582949, by Cayman Chemical (2 mentions) Accuri c6, by BD (2 mentions) Bafilomycin a1, by Bio-Techne (2 mentions) Sb203580, by Bio-Techne (2 mentions) Fla st ultrapure, by InvivoGen (1 mentions) Sch772984, by Chemietek (1 mentions) U0126, by Bio-Techne (1 mentions) Dual luciferase reporter assay system, by Promega (1 mentions) Skf96365, by Bio-Techne (1 mentions) Xestospongin c, by Santa Cruz Biotechnology (1 mentions) Trans ned19, by Bio-Techne (1 mentions) 8 br adpr, by Biolog (1 mentions)

Spelling variants of this product

5,6,7,13-tetrahydro-13-methyl-5-oxo-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-12-propanenitrile (Go6976) (2 citations)

22 protocols using go6976

Flagellin and Kinase Inhibitor Combination

Cited 1 time

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FLA-ST Ultrapure (purified flagellin from Salmonella Typhimurium, a TLR5 agonist) and the vehicle solution, endotoxin-free water, were purchased from InvivoGen (San Diego, CA, USA). In this experiment, it was applied at 0.1 μg, 0.3 μg and 0.9 μg in 10 μL vehicle solution separately, which was modified from the previous procedure of intraplantar administration with flagellin [19 (link)].
Go 6976 was purchased from Tocris Bioscience (Ellisville, MO, USA) and prepared in 0.1% DMSO in 0.1 M PB [57 (link)]. FLA-ST Ultrapure 0.9 μg (InvivoGen, San Diego, CA, USA) was used to combine with Go 6976, which separated into four subgroups (0 μM, 5 μM, 20 μM and 50 μM; n = 3 per subgroup) respectively. Likewise, DAMGO 25 μg (Tocris Bioscience, Ellisville, MO, USA) was used to combine with Go 6976 and also assigned into four subgroups separately.

Chang C., Liu H.K., Yeh C.B., Yang M.L., Liao W.C., Liu C.H, & Tseng T.J. (2021). Cross-Talk of Toll-Like Receptor 5 and Mu-Opioid Receptor Attenuates Chronic Constriction Injury-Induced Mechanical Hyperalgesia through a Protein Kinase C Alpha-Dependent Signaling. International Journal of Molecular Sciences, 22(4), 1891.

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Inhibitor Screening for Cell Signaling

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U0126 (Cat. # 1144, MEK inhibitor) and Go6976 (Cat. # 2253/1, PKCα inhibitor) were purchased from TOCRIS (Bristol UK). TBCA (Cat. # 934358–00–6, CK2 inhibitor) and S2101 (Cat. # 48977, LSD1 inhibitor) were purchased from Calbiochem (San Diego, CA, USA). SCH772984 (Cat. # CT-SCH772, ERK inhibitor) and Tamoxifen were purchased from Chemie Tek (Indianapolis, IN, USA) and Sigma, respectively. Dual-Luciferase Reporter Assay system was purchased from Promega (Madison, WI, USA).

Lee K., Kitagawa M., Liao P.J., Virshup D.M, & Lee S.H. (2020). A Ras-LSD1 axis activates PI3K signaling through PIK3IP1 suppression. Oncogenesis, 9(1), 2.

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Inhibitors of Sarcoplasmic Reticulum Calcium Release

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Xestospongin C was obtained from Santa Cruz Biotechnology. Trans-Ned19, GF10923X, Go6976, rottlerin, and SKF96365 were obtained from Tocris Bioscience. 8-Br-ADPR and ara-2’-F-NAD were obtained from Biolog Life Science Institute. All other reagents were obtained from Sigma-Aldrich.

Rah S.Y., Joe Y., Park J., Ryter S.W., Park C., Chung H.T, & Kim U.H. (2023). CD38/ADP-ribose/TRPM2-mediated nuclear Ca2+ signaling is essential for hepatic gluconeogenesis in fasting and diabetes. Experimental & Molecular Medicine, 55(7), 1492-1505.

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Characterization of Signaling Pathways

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Isoproterenol, formoterol, GO6983, GO6976, RO32–0432, GF109203X, H89, PSB603, ESI-09, TPPB, NECA (adenosine-5′-N-ethyluronamide), MRS5698 and MRS2365 ([[(1R,2R,3S,4R,5S)-4-[6-amino-2-(methylthio)-9H-purin-9-yl]-2,3-dihydroxybicyclo[3.1.0]hex-1-yl]methyl] diphosphoric acid monoester trisodium salt) were purchased from Tocris (Ellisville, MO). CGS21680">CGS21680, carbachol, cholera toxin (CTX) and PTX were from Sigma (St. Louis, MO). YM254890, enzastaurin, LY333531, VTX-27 and AB928 were purchased from MedChemExpress (Monmouth Junction, NJ, USA). BAY60-6583 (LUF6210, termed hereafter ‘BAY’) was synthesized at Leiden/Amsterdam Center for Drug Research and was provided by Ad IJzerman (Leiden, The Netherlands). All compounds were dissolved in DMSO except that CTX and PTX were in water, and proper controls were included in all experiments. AlphaScreen cAMP kit, SureFire p-ERK1/2 (Thr202/Tyr204) Assay Kit and AlphaScreen SureFire p-Akt 1/2/3 (p-Ser473) Assay Kit were purchased from PerkinElmer (Waltham, MA). G_s-null and G_q/11-null HEK293 cells were generated at Tohoku University, Sendai, Japan. HEK293 human embryonic kidney, PC-3 human prostate cancer, NIH-3T3 mouse fibroblast, and H9C2 rat cardiomyoblast cells were from ATCC (Manassas, VA); all other reagents were from standard commercial sources and of analytical grade.

Gao Z.G., Levitan I.M., Inoue A., Wei Q, & Jacobson K.A. (2023). A2B adenosine receptor activation and modulation by protein kinase C. iScience, 26(7), 107178.

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Ang II-Induced Vascular Remodeling

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GF 109203X was purchased from Calbiochem. Ang II, losartan, Go 6976, apocynin, and ML-171 were obtained from Tocris. Primary antibodies against Ca_V3.2, Ca_V3.1 and Nox1 were purchased from Novus Biologicals. Duolink PLA detection kit and all other chemicals were obtained from Sigma Aldrich. Data are expressed as means ± S.E., and n indicates the number of cells or arteries or animals. Paired t-test was performed to compare the effects of a given condition/treatment on whole cell current or arterial diameter. P values ≤ 0.05 were considered statistically significant.

Hashad A.M., Sancho M., Brett S.E, & Welsh D.G. (2018). Reactive Oxygen Species Mediate the Suppression of Arterial Smooth Muscle T-type Ca2+ Channels by Angiotensin II. Scientific Reports, 8, 3445.

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Platelet activation signaling pathways

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MRS2395 [2,2-Dimethyl-propionic acid 3-(2-chloro-6-methylaminopurin-9-yl)-2-(2,2-dimethyl-propionyloxymethyl)-propyl
ester], adenosine diphosphate (ADP), wortmannin, thrombin and all other chemicals and reagents were purchased from Sigma-Aldrich
(St Louis, MO, USA) or previously mentioned sources unless specified otherwise.[12 (link), 13 (link)] TRAP-6 (SFLLRN), U73122, U73343, Ro 31–8220, Rottlerin, Go6976, MRS2179, BAPTA,
PSB 0739 and AR-C 66096 were obtained from Tocris (Bristol, UK). Ticagrelor was purchased from Oxchem Corporation (Wood Dale, IL,
USA). AYPGKF-NH₂ was obtained from Abgent (San Diego, CA, USA). Oregon Green® 488 BAPTA-1 AM (OG488 BAPTA-1 AM)
was from Thermo Fisher Scientific (Carlsbad, CA, USA). PAC-1-FITC and anti-CD62P-APC were obtained from BD Bioscience (San Jose,
CA, USA). Anti-AKT, phospho (p)AKT-Ser473, pGSK3β-Ser9 and pPKC-Ser substrates were from Cell Signaling Technology
(Danvers, MA, USA).

Mitrugno A., Rigg R.A., Laschober N.B., Ngo A.T., Pang J., Williams C.D., Aslan J.E, & McCarty O.J. (2017). Potentiation of TRAP-6-induced platelet dense granule release by blockade of P2Y12 signaling with MRS2395. Platelets, 29(4), 383-394.

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Investigating IL-10 mRNA Regulation

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HNE with 81 U/mg of activity was purchased
from SERVA Electrophoresis (Heidelberg, Germany).
3,4,5-trimethoxybenzoic acid 8-(diethylamino)
octyl ester (TMB-8, Sigma-Aldrich,
Canada), A23187 (Santa Cruz Biotechnology,
USA), Rottlerin Tumor necrosis factor-alpha
(TNF-α)protease inhibitor I (TAPI-1), U73122,
R59022 (Merck Millipore, USA), and pyrrolidinedithiocarbamate
(PDTC, BioVision, USA)
were employed to investigate the intracellular
signal transduction pathways involved in IL-10
mRNA expression. The actions of these reagents
are summarized in table 1.
In addition, PKC inhibitors including Ro-
318425 (Merck Millipore), Go 6976, Go 6983,
and CGP 41251 (Tocris Bioscience, UK), as
well as a PKC theta/delta inhibitor (Merck Millipore)
were utilized to investigate the roles of
PKC isoforms in IL-10 production. The PKC
isoform-specific inhibition profile of these reagents
is summarized in table 2.
Xestospongin C, which antagonizes the calciumreleasing
action of IP3 at the receptor level, was
obtained from Sigma-Aldrich, USA. Each reagent
solution was negative for endotoxin according to
the Endospecy test (22 (link), 23 (link)).

Kawata J., Yamaguchi R., Yamamoto T., Ishimaru Y., Sakamoto A., Aoki M., Kitano M., Umehashi M., Hirose E, & Yamaguchi Y. (2016). Human Neutrophil Elastase Induce Interleukin-10 Expression in Peripheral Blood Mononuclear Cells through Protein Kinase C Theta/Delta and Phospholipase Pathways. Cell Journal (Yakhteh), 17(4), 692-700.

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Pharmacological Agents in Experimental Study

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GFX, Go6976 and Go6983 were purchased from Tocris Bioscience (Bristol, UK). All other drugs and chemicals used in this study were obtained from Sigma-Aldrich (St. Louis, MO, USA). Phenylephrine, Acetylcholine, catalase and Y27632 were dissolved in water. DMSO solvent was used in all other drugs included plumbagin. Stock solutions of drugs dissolved in DMSO in the bath never exceeded 0.01%.

Kim H.J., Yoo H.Y., Zhang Y.H., Kim W.K, & Kim S.J. (2017). Biphasic augmentation of alpha-adrenergic contraction by plumbagin in rat systemic arteries. The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology, 21(6), 687-694.

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Caspase-3/7 Activity Assay for Chemotherapy

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Cells treatments were as follows: 1.7μM Daunorubicin (chemotherapy, Sigma-Aldrich), 1μM Cytarabine (chemotherapy, Tocris), 1μM GO6976 (PKC inhibitor, Tocris), 20nM BIO5192 (VLA-4 inhibitor, Tocris) or 25nM BMS 582949 (p38 MAP kinase inhibitor, Cayman Chemical) individually or in combination as stated. Caspase-3/−7 activity was measured with the CellEvent™ Caspase-3/7 Green Flow Cytometry Assay Kit as indicated by manufacturer (Thermo Fisher). Cells were analyzed using an Accuri C6 flow cytometer (BD Bioscience) and percent caspase positive cells were normalized to unstained controls.

Floren M., Cruz S.R., Termini C.M., Marjon K.D., Lidke K.A, & Gillette J.M. (2020). Tetraspanin CD82 drives Acute Myeloid Leukemia chemoresistance by modulating Protein Kinase C alpha and β1 integrin activation. Oncogene, 39(19), 3910-3925.

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Caspase-3/7 Activity Assay for Chemotherapy

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