PCI-32765 (RaceMate)

Definition

ChEBI: 1-[3-[4-amino-3-(4-phenoxyphenyl)-1-pyrazolo[3,4-d]pyrimidinyl]-1-piperidinyl]-2-propen-1-one is an aromatic ether.

Biological Activity

pci-32765 is an inhibitor of bruton tyrosine kinase (btk) with ic50 value of 0.5nm [1].pci-32765 is a covalent and irreversible inhibitor of btk through bonding to cys-481 in the atp binding domain. pci-32765 inhibits phosphorylation of btk in a b cells (ic50 of 11nm) as well as the downstream substrates phosphoinositide phospholipase cγ (plc γ) and erk in cell assays. pci-32765 has in vivo efficacy in b cell lymphoma. in cll cells, pci-32765 induces cells apoptosis through inhibiting the expression of bcr-dependent udp-glucose ceramide glucosyltransferase [1].pci-32765 is oral effective in vivo. it induces lymphocytosis during the first weeks of therapy in patients with cll. it is also efficacious in autoimmune disease. in the mrl-fas lupus model, pci-32765 inhibits collagen-induced arthritis as well as autoantibody production and development of kidney disease. it also diminished fcγriii-induced production of pro-inflammatory cytokines [1].

References

[1] burger ja, buggy jj. bruton tyrosine kinase inhibitor ibrutinib (pci-32765). leuk lymphoma. 2013 nov;54(11):2385-91.