Synonym
GO6976; GO-6976; GO 6976; Goe 6976; Goe6976; Goe-6976; PD406976; PD 406976; PD-406976.
IUPAC/Chemical Name
3-(13-methyl-5-oxo-6,7-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12(13H)-yl)propanenitrile
InChi Key
VWVYILCFSYNJHF-UHFFFAOYSA-N
InChi Code
InChI=1S/C24H18N4O/c1-27-17-9-4-2-7-14(17)20-21-16(13-26-24(21)29)19-15-8-3-5-10-18(15)28(12-6-11-25)23(19)22(20)27/h2-5,7-10H,6,12-13H2,1H3,(H,26,29)
SMILES Code
N#CCCN(C1=C2C(CNC3=O)=C3C4=C1N(C)C5=C4C=CC=C5)C6=C2C=CC=C6
Appearance
white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Go6976 is a Protein Kinase C (PKC) inhibitor, with an IC50 of 20 nM.
In vitro activity:
In vitro experiments were conducted to explore the effect of Gö6976 on leukemia cells. The CCK-8 assay results showed that the optical density (OD) of K562 cells in the Gö6976 groups was decreased at 24, 48 and 72 h compared with that in the control group. To further explore whether Gö6976 affects the anti-CML effect of TKIs, imatinib was added for the study. At the same time, the proliferation of K562 cells in the groups treated with imatinib and Gö6976 was more inhibited than in the group treated with imatinib alone, and the difference was statistically significant. The above results indicate that Gö6976 has a significant inhibitory effect on the growth of K562 cells and can enhance the sensitivity of K562 cells to imatinib.
Reference: Hematology. 2021 Dec;26(1):543-551. https://pubmed.ncbi.nlm.nih.gov/34348586/
In vivo activity:
To explore the effects of Gö6976 in the body, a mouse model of CML was created. Mice began to develop leukemic symptoms at approximately 3 weeks after injection of tumor cells. Compared with the control group, the mice in the Gö6976 group had significantly less weight loss 5 weeks after injection. The number of WBCs in the 2.5 mg/kg Gö6976 group was significantly decreased compared with that in the control group from the 3rd to the 5th weeks. At the fourth week, the CD45+ leukemia cells in the 2.5 mg/kg Gö6976 group were significantly fewer than those in the control group. The survival time of the mice in the 2.5 mg/kg Gö6976 group was significantly longer than that of the mice in the control group. In summary, Gö6976 can directly inhibit the progression of CML and effectively increase the survival rate of mice.
Reference: Hematology. 2021 Dec;26(1):543-551. https://pubmed.ncbi.nlm.nih.gov/34348586/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
25.0 |
67.26 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
378.44
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Cao ZR, Chen XP, Feng M, Hou YL, Li Y, Hu XL, Huang ZL, Hu J. The effect of Gö6976 on chronic myeloid leukemia in vitro and in vivo. Hematology. 2021 Dec;26(1):543-551. doi: 10.1080/16078454.2021.1945235. PMID: 34348586.
2. Yoshida A, Ookura M, Zokumasu K, Ueda T. Gö6976, a FLT3 kinase inhibitor, exerts potent cytotoxic activity against acute leukemia via inhibition of survivin and MCL-1. Biochem Pharmacol. 2014 Jul 1;90(1):16-24. doi: 10.1016/j.bcp.2014.04.002. Epub 2014 Apr 13. PMID: 24735609.
3. Yoon TW, Kim YI, Cho H, Brand DD, Rosloniec EF, Myers LK, Postlethwaite AE, Hasty KA, Stuart JM, Yi AK. Ameliorating effects of Gö6976, a pharmacological agent that inhibits protein kinase D, on collagen-induced arthritis. PLoS One. 2019 Dec 6;14(12):e0226145. doi: 10.1371/journal.pone.0226145. PMID: 31809526; PMCID: PMC6897462.
In vitro protocol:
1. Cao ZR, Chen XP, Feng M, Hou YL, Li Y, Hu XL, Huang ZL, Hu J. The effect of Gö6976 on chronic myeloid leukemia in vitro and in vivo. Hematology. 2021 Dec;26(1):543-551. doi: 10.1080/16078454.2021.1945235. PMID: 34348586.
2. Yoshida A, Ookura M, Zokumasu K, Ueda T. Gö6976, a FLT3 kinase inhibitor, exerts potent cytotoxic activity against acute leukemia via inhibition of survivin and MCL-1. Biochem Pharmacol. 2014 Jul 1;90(1):16-24. doi: 10.1016/j.bcp.2014.04.002. Epub 2014 Apr 13. PMID: 24735609.
In vivo protocol:
1. Cao ZR, Chen XP, Feng M, Hou YL, Li Y, Hu XL, Huang ZL, Hu J. The effect of Gö6976 on chronic myeloid leukemia in vitro and in vivo. Hematology. 2021 Dec;26(1):543-551. doi: 10.1080/16078454.2021.1945235. PMID: 34348586.
2. Yoon TW, Kim YI, Cho H, Brand DD, Rosloniec EF, Myers LK, Postlethwaite AE, Hasty KA, Stuart JM, Yi AK. Ameliorating effects of Gö6976, a pharmacological agent that inhibits protein kinase D, on collagen-induced arthritis. PLoS One. 2019 Dec 6;14(12):e0226145. doi: 10.1371/journal.pone.0226145. PMID: 31809526; PMCID: PMC6897462.
1: Jung SY, Kim OB, Kang HK, Jang da H, Min BM, Yu FH. Protein kinase Cα/β inhibitor Gö6976 promotes PC12 cell adhesion and spreading through membrane recruitment and activation of protein kinase Cδ. Exp Cell Res. 2013 Feb 1;319(3):153-60. doi: 10.1016/j.yexcr.2012.10.003. Epub 2012 Oct 9. PubMed PMID: 23063429.
2: Thompson R, Meuth M, Woll P, Zhu Y, Danson S. Treatment with the Chk1 inhibitor Gö6976 enhances cisplatin cytotoxicity in SCLC cells. Int J Oncol. 2012 Jan;40(1):194-202. doi: 10.3892/ijo.2011.1187. Epub 2011 Sep 5. PubMed PMID: 21894433.
3: Robinson JW, Potter LR. ATP potentiates competitive inhibition of guanylyl cyclase A and B by the staurosporine analog, Gö6976: reciprocal regulation of ATP and GTP binding. J Biol Chem. 2011 Sep 30;286(39):33841-4. doi: 10.1074/jbc.M111.273565. Epub 2011 Aug 2. PubMed PMID: 21828054; PubMed Central PMCID: PMC3190780.
4: Robinson JW, Lou X, Potter LR. The indolocarbazole, Gö6976, inhibits guanylyl cyclase-A and -B. Br J Pharmacol. 2011 Sep;164(2b):499-506. doi: 10.1111/j.1476-5381.2011.01291.x. PubMed PMID: 21366551; PubMed Central PMCID: PMC3188892.
5: Getz TM, Mayanglambam A, Daniel JL, Kunapuli SP. Go6976 abrogates GPVI-mediated platelet functional responses in human platelets through inhibition of Syk. J Thromb Haemost. 2011 Mar;9(3):608-10. doi: 10.1111/j.1538-7836.2011.04192.x. PubMed PMID: 21251194; PubMed Central PMCID: PMC3057064.
6: Duan GJ, Zhu J, Xu CY, Wan JY, Zhang L, Ge XD, Liu LM, Liu YS. Protective effect of Gö6976, a PKD inhibitor, on LPS/D: -GalN-induced acute liver injury in mice. Inflamm Res. 2011 Apr;60(4):357-66. doi: 10.1007/s00011-010-0278-1. Epub 2010 Nov 10. PubMed PMID: 21063746.
7: Aaltonen V, Peltonen J. PKCalpha/beta I inhibitor Go6976 induces dephosphorylation of constitutively hyperphosphorylated Rb and G1 arrest in T24 cells. Anticancer Res. 2010 Oct;30(10):3995-9. PubMed PMID: 21036713.
8: Feng Z, Xu S, Liu M, Zeng YX, Kang T. Chk1 inhibitor Gö6976 enhances the sensitivity of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy in vitro and in vivo. Cancer Lett. 2010 Nov 28;297(2):190-7. doi: 10.1016/j.canlet.2010.05.011. Epub 2010 Jul 8. PubMed PMID: 20619533.
9: Jia XZ, Yang SY, Zhou J, Li SY, Ni JH, An GS, Jia HT. Inhibition of CHK1 kinase by Gö6976 converts 8-chloro-adenosine-induced G2/M arrest into S arrest in human myelocytic leukemia K562 cells. Biochem Pharmacol. 2009 Mar 1;77(5):770-80. doi: 10.1016/j.bcp.2008.11.008. Epub 2008 Nov 18. PubMed PMID: 19059218.
