Ibrutinib

Ibrutinib (PCI-32765, PCI32765) is a potent and highly selective Btk inhibitor with IC50 of 0.5 nM; modestly potent to Bmx, CSK, FGR, BRK, HCK, less potent to EGFR, Yes, ErbB2, JAK3, etc.Blood Cancer Approved (In Vitro) :Ibrutinib (PCI-32765) selectively inhibits B-cell signaling and activation. It inhibits autophosphorylation of Btk (IC50=11 nM), phosphorylation of Btk's physiological substrate PLCγ (IC50=29 nM), and phosphorylation of a further downstream kinase, ERK (IC50=13 nM) .Ibrutinib (PCI-32765) inhibits BCR-activated primary B cell proliferation (IC50=8 nM) . Following FcγR stimulation, Ibrutinib (PCI-32765) inhibits TNFα, IL-1β and IL-6 production in primary monocytes (IC50=2.6, 0.5, 3.9 nM, respectively) .Ibrutinib binds C481 (Cysteine481) of BTK with an ideal IC50 of 0.5 nM. Ibrutinib cannot form a covalent bond with the hydroxyl group of serine, C481S mutation increases the IC50 against BTK-C481S phosphorylation from 2.2 nM to 1 μM. (In Vivo) :Ibrutinib (PCI-32765) (3.125-50 mg/kg, p.o.) reduces the level of circulating autoantibodies and completely suppresses disease in mice with collagen-induced arthritis. Ibrutinib (PCI-32765) inhibits autoantibody production and the development of kidney disease in the MRL-Fas (lpr) lupus model. Ibrutinib (PCI-32765) (3.125-50 mg/kg, p.o.) reduces renal disease and autoantibody production in MRL-Fas (lpr) mice. Ibrutinib (PCI-32765) (0.1 μM) inhibits activation-induced proliferation of CLL cells, induces selective cytotoxicity in B cells compared with T cells, but alters activation induced T-cell cytokine production. Ibrutinib (PCI-32765) dose-dependently and potently reverses arthritic inflammation in a therapeutic CIA model with an ED50 of 2.6 mg/kg/day. Ibrutinib (PCI-32765) also prevents clinical arthritis in CAIA models.

936563-96-1

PCI-32765 | PCI32765 | PCI 32765

Pharmacology & Drug Discovery

>98% (HPLC)

DMSO: ≥ 52 mg/mL

C=CC (N1C[C@H] (N2N=C (C3=CC=C (OC4=CC=CC=C4) C=C3) C5=C (N) N=CN=C52) CCC1) =O

C25H24N6O2

440.4971

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.