PRT062607 hydrochloride

Research use only, not for human use.

PRT062607 (P505-15, BIIB057) hydrochloride is a novel, highly selective Syk inhibitor with IC50 of 1 nM in cell-free assays.

PRT062607 (P505-15, BIIB057) hydrochloride is a novel, highly selective Syk inhibitor with IC50 of 1 nM in cell-free assays, >80-fold selective for Syk than Fgr, Lyn, FAK, Pyk2 and Zap70.(In Vitro):PRT062607 (P505-15) is a novel, highly specific, and potent orally available small-molecule inhibitor of Syk. The potency of PRT062607 against its target kinase Syk is initially tested in two different purified kinase assays. Using a FRET assay, half-maximal Syk inhibition required 6±0.2 nM (mean±S.E.M.). Similar potency is observed when tested in a radioactive enzyme assay, with a resulting Syk IC50 of 2.1±0.4 nM (mean±S.E.M.). In human whole blood, PRT062607 potently inhibits B cell antigen receptor-mediated B cell signaling and activation (IC50 0.27 and 0.28 μM, respectively) and Fcε receptor 1-mediated basophil degranulation (IC50 0.15 μM).(In Vivo):In the mouse CAIA model, oral administration of PRT062607 (P505-15) results in an average inhibition of paw inflammation, as measured by daily scoring of inflammation compared with vehicle controls, of 12, 44, and 87% with average plasma concentration (C average over 24 h) assessed at the end of the study of 0.38, 0.95, and 1.47 μM, respectively. In mice treated with 30 mg/kg PRT062607, the damage to the joints is significantly reduced and seemed indistinguishable from normal mice. In the rat CIA model, the high dose of PRT062607 (15 mg/kg b.i.d.) completely suppresses inflammation in a majority of the animals (seven of eight), by the end of the study (mean inflammation score±S.E.M.=0.63±1.1; p<0.0001 versus vehicle).

PRT062607 (P505-15) is a novel, highly specific, and potent orally available small-molecule inhibitor of Syk. The potency of PRT062607 against its target kinase Syk is initially tested in two different purified kinase assays. Using a FRET assay, half-maximal Syk inhibition required 6±0.2 nM (mean±S.E.M.). Similar potency is observed when tested in a radioactive enzyme assay, with a resulting Syk IC50 of 2.1±0.4 nM (mean±S.E.M.). In human whole blood, PRT062607 potently inhibits B cell antigen receptor-mediated B cell signaling and activation (IC50 0.27 and 0.28 μM, respectively) and Fcε receptor 1-mediated basophil degranulation (IC50 0.15 μM).

In the mouse CAIA model, oral administration of PRT062607 (P505-15) results in an average inhibition of paw inflammation, as measured by daily scoring of inflammation compared with vehicle controls, of 12, 44, and 87% with average plasma concentration (C average over 24 h) assessed at the end of the study of 0.38, 0.95, and 1.47 μM, respectively. In mice treated with 30 mg/kg PRT062607, the damage to the joints is significantly reduced and seemed indistinguishable from normal mice. In the rat CIA model, the high dose of PRT062607 (15 mg/kg b.i.d.) completely suppresses inflammation in a majority of the animals (seven of eight), by the end of the study (mean inflammation score±S.E.M.=0.63±1.1; p<0.0001 versus vehicle).

P505-15, BIIB057

Angiogenesis

FLT

FLT3| MLK1| FGR| Yes| Syk

Cancer

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1370261-97-4

429.91

C19H23N9O·HCl

>98% (HPLC)

Water: 86 mg/mL (200.04 mM); DMSO: 86 mg/mL (200.04 mM)

C1CC[C@H]([C@H](C1)N)NC2=NC=C(C(=N2)NC3=CC=CC(=C3)N4N=CC=N4)C(=O)N.Cl

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(-20℃)

With Ice Pack

≥ 2 years