PCI-29732

Biological Activity

PCI-29732 is a potent, reversible BTK inhibitor. PCI-29732 blocks B cell antigen receptor (BCR)-mediated gene expression in CD20+ B cells. PCI-29732 inhibits the function of ABCG2 by competitively binding to the ATP-binding site of ABCG2 and enhances the anti-tumor efficacy of substrate chemotherapeutic agents. In vivo, PCI-29732 (20 mg/kg; p.o.; 5 times/3 days) enhances the anticancer efficacy of Topotecan in the H460/MX20 cell xenograft nude mice model.

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

PCI29732, a Bruton's Tyrosine Kinase Inhibitor, Enhanced the Efficacy of Conventional Chemotherapeutic Agents in ABCG2-Overexpressing Cancer Cells
Chunlei Ge, et al. Cell Physiol Biochem. 2018;48(6):2302-2317. PMID: 30114704.

The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy
Lee A Honigberg, et al. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13075-80. PMID: 20615965.