PRT062607 (acetate)

PRT062607 (P505-15) acetate is an orally available Syk inhibitor (IC₅₀: 1 nM) that inhibits inflammation and induction Apoptosis. PRT062607 acetate exerts potent antitumor activity in tumor xenograft mouse models^[1].^[2]. IC50 & Target:IC50: 1 nM (Syk), 81 nM (Fgr), 88 nM (MLK1), 123 nM (Yes)^[1] In Vitro:PRT062607 acetate also has significant activity against multiple kinases, with IC₅₀s of 81 nM (Fgr), 88 nM (MLK1), 123 nM (Yes), 139 nM (Flt3), 166 nM (PAK5), 192 nM (Lyn), 244 nM (cSRC), 249 nM (Lck), 108 nM (Pyk), 415 nM (FAK), 1.05 nM (ZAP-70)^[1].
PRT062607 acetate (0.01-2 μM; 3 d) inhibits Phosphorylation of ERK(Y204), AKT(S473) and SYK(Y352) in Ramos cells, and inhibition of BLNK Tyr84 phosphorylation^[1][2].
PRT062607 acetate (2 μM; 24 h) in SU-DHL6 cells Induces apoptosis in human whole blood^[1].
In human whole blood, P505-15 can effectively inhibit B cell antigen receptor-mediated B cell signaling and activation (IC₅₀: 0.27 and 0.28 μM) and Fc receptor 1-mediated induced basophil degranulation (IC₅₀: 0.15 μM)^[2].
In Vivo:PRT062607 acetate produced dose-dependent anti-inflammatory activity in two rodent models of rheumatoid arthritis. PRT062607 acetate (15, 30 mg/kg; po; bid; 5 d) causes SYK inhibition in mice and prevents BCR-induced splenomegaly in mice^[1].
PRT062607 acetate (15 mg/kg; po ; bid; 5 d) SYK inhibition in mice prevents Ramos tumor formation in mouse xenograft models^[1].
PRT062607 acetate (10-20 mg/kg; po; bid) prevents BCR mediated splenomegaly and significantly inhibited NHL tumor growth in xenograft models^[2].