Go 6983

Biological Activity

Go 6983 is a protein kinase C (PKC) inhibitor with IC50 values of 7 nM, 7 nM, 6 nM, 10 nM and 60 nM for PKCα, PKCβ, PKCγ, PKCδ and PKCζ respectively. Go 6983 inhibited intracellular Ca(2+) accumulation, suggesting a mechanism for its vasodilator properties. In vitro, Go 6983 significantly inhibited antigen-induced superoxide release from leukocytes of patients previously sensitized to tree pollen. Go 6983 (100 nM) significantly reduced PMN adherence to the endothelium and infiltration into the myocardium compared with I/R + PMN hearts (P < 0.01), and significantly inhibited superoxide release from PMNs by 90 +/- 2% (P < 0.01). Go 6983 attenuated post-I/R cardiac contractile dysfunction, which may be related in part to decreased superoxide production in the presence of PMNs.

Customer Product Validations & Biological Datas

	Source	Immunobiology (2012). Figure 4. Go 6983
	Method	Flow cytometry
	Cell Lines	Tca8113 cells
	Concentrations	5 μM
	Incubation Time	24 h
	Results	As shown in Fig. 4, after PKD2 was inhibited by Gö6983, IFN-γ could not induce the surface expression of PD-L1 on Tca8113.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information

References

Gö 6983: a fast acting protein kinase C inhibitor that attenuates myocardial ischemia/reperfusion injury.
Young LH, et al. Cardiovasc Drug Rev. 2005 Fall;23(3):255-72. PMID: 16252018.

Protein kinase C-independent effects of protein kinase D3 in glucose transport in L6 myotubes.
Chen J, et al. Mol Pharmacol. 2005 Jan;67(1):152-62. PMID: 15496505.

Gö 6983 exerts cardioprotective effects in myocardial ischemia/reperfusion.
Peterman EE, et al. J Cardiovasc Pharmacol. 2004 May;43(5):645-56. PMID: 15071351.