PF-06465469

PF-06465469 is a covalent inhibitor of IL-2-inducible T cell kinase (Itk, IC50 = 2 nM). It also inhibits Bruton's tyrosine kinase (BTK, IC50 = 2 nM). PF-06465469 inhibits Itk phosphorylation of phospholipase Cgamma (PLCgamma) induced by an anti-CD3 antibody in Jurkat cells (IC50 = 57 nM). It induces apoptosis in Jurkat cells, MOLT-4 and CCRF CEM T cell lymphoblasts, and Karpas-299 large cell lymphoma cells when used at a concentration of 16 µM. PF-06465469 (2 µM) inhibits chemotaxis induced by chemokine (C-X-C motif) ligand 12 (CXCL12) in Jurkat cells. SMILES NC1=C(C(C2=CC=CC(C(NC3=CC(C)=C(C(C)C)C=C3)=O)=C2)=NN4[C@@]5([H])CN(C(C=C)=O)CCC5)C4=NC=N1 InChi Code InChI=1S/C30H33N7O2/c1-5-25(38)36-13-7-10-23(16-36)37-29-26(28(31)32-17-33-29)27(35-37)20-8-6-9-21(15-20)30(39)34-22-11-12-24(18(2)3)19(4)14-22/h5-6,8-9,11-12,14-15,17-18,23H,1,7,10,13,16H2,2-4H3,(H,34,39)(H2,31,32,33)/t23-/m1/s1 InChi Key CGJVMKJGKFEHTL-HSZRJFAPSA-N