GO-6976
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MedKoo CAT#: 406206

CAS#: 136194-77-9

Description: GO 6976, also known as PD-406976, is a potent inhibitor of neurotrophin-receptor intrinsic tyrosine kinase. Gö 6976 blocked neurotrophin-induced signaling and autophosphorylation of neurotrophin-specific tyrosine kinase (Trk) receptors, either Trk B in cortical neurons or Trk A in GT1-1-trk9 cells.

Chemical Structure

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GO-6976
CAS# 136194-77-9
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 406206
Name: GO-6976
CAS#: 136194-77-9
Chemical Formula: C24H18N4O
Exact Mass: 378.15
Molecular Weight: 378.435
Elemental Analysis: C, 76.17; H, 4.79; N, 14.81; O, 4.23

Price and Availability

Size Price Availability Quantity
50mg USD 2950 2 Weeks
100mg USD 4250 2 Weeks
200mg USD 5950 2 Weeks
500mg USD 7950 2 Weeks
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Synonym: GO6976; GO-6976; GO 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

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Product Data:
Product Data
Instruction:
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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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 25.0 67.26

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.

Recalculate based on batch purity %
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.

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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.