EBE-A22

Biological Activity

EBE-A22 is a derivative of PD 153035. EBE-A22, has no effect on EGF-R TK but maintains a high cytotoxic profile. EBE-A22 binds to DNA and behave as typical intercalating agents. EBE-A22 unwinds supercoiled plasmid, stabilizes duplex DNA against heat denaturation, and produces negative CD and ELD signals, as expected for an intercalating agent.

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 resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 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 resveratrol of 11.2 mg/kg.

Chemical Information

References

Upregulation of retinoic acid receptor-beta by the epidermal growth factor-receptor inhibitor PD153035 is not mediated by blockade of ErbB pathways.
Grunt TW, et al. J Cell Physiol. 2007 Jun;211(3):803-15. PMID: 17286282.

DNA interaction of the tyrosine protein kinase inhibitor PD153035 and its N-methyl analogue.
Goossens JF, et al. Biochemistry. 2001 Apr 17;40(15):4663-71. PMID: 11294633.