NVP-ACC789

Biological Activity

NVP-ACC789, also known as ACC-789 and ZK-202650, is a potent, selective and orally active inhibitor of the VEGF receptor tyrosine kinases with potential anticancer activity. NVP-ACC789 reduces BME cell number to baseline levels from 1 μM. NVP-ACC789 also completely inhibits VEGF-induced BME and BAE cell invasion and VEGF-C-induced BAE cell invasion. The inhibition is dose-dependent in both cell types with a maximal effect from 1 μM. 

In Vivo, NVP-ACC789 oral doses for 6 days blocks VEGF-induced angiogenesis in a dose-dependent manner.

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

Vascular endothelial growth factor (VEGF) receptor-2 antagonists inhibit VEGF- and basic fibroblast growth factor-induced angiogenesis in vivo and in vitro.
Tille JC, et al. J Pharmacol Exp Ther. 2001 Dec;299(3):1073-85. PMID: 11714897.