1. Protein Tyrosine Kinase/RTK
  2. Btk

PCI-32765 (Synonyms: Ibrutinib)

Cat. No.: HY-10997 Purity: 99.87% ee.: 99.50%
Data Sheet SDS Handling Instructions

PCI-32765 is a selective, irreversible Btk inhibitor with IC50 value of 0.5 nM.

For research use only. We do not sell to patients.
PCI-32765 Chemical Structure

PCI-32765 Chemical Structure

CAS No. : 936563-96-1

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $55 In-stock
10 mg $50 In-stock
50 mg $70 In-stock
100 mg $90 In-stock
200 mg $110 In-stock
500 mg $190 In-stock
1 g $290 In-stock
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Other Forms of PCI-32765:

    PCI-32765 purchased from MCE. Usage Cited in: Oncotarget. 2015 Oct 13;6(31):31313-22.

    Effect of Ibrutinib on EGFR wt/mutant NSCLCs. Ibrutinib effects on wt EGFR and mutant EGFR- mediated signaling pathways. The results demonstrate that Ibrutinib potently inhibits both EGFR wt/mutant auto-phosphorylation at Y1068.

    PCI-32765 purchased from MCE. Usage Cited in: Oncotarget. 2015 Oct 13;6(31):31313-22.

    Effect of Ibrutinib, WZ4002, AZD9291 and CO1686 on EGFR phosphorylation of tyrosines 1068 and 1173 in EGFR-dependent cancer cell lines.

    PCI-32765 purchased from MCE. Usage Cited in: Mol Cell Proteomics. 2012 Jun;11(6):M112.017764.

    Btk protein tyrosine kinase is involved in TSLP signaling. Western blotting analysis is performed to demonstrate the roles of Btk in TSLP-induced Stat3 and Stat5 phosphorylation. Exponentially growing Ba/F3-IT cells are pretreated with 0.1% DMSO or 1 μM PCI-32765 or 10 μM PCI-32765 for 1 h at 37 °C and then are stimulated with TSLP for the indicated times at 37 °C. The phosphorylation of Btk, Stat3, and Stat5a is probed with phosphospecific antibodies against p-Btk (Y551), p-Stat3 (Y705), and p-

    PCI-32765 purchased from MCE. Usage Cited in: Br J Haematol. 2015 Jul;170(1):134-8.

    Treatment of CXCR4WT and CXCR4S338X BCWM.1 and MWCL-1 cells with Ibrutinib or Idelalisib induced caspase-3 and PARP cleavage at 6 h. Caspase-3 and PAPR cleavage following Ibrutinib (IB), Idelalisib (ID), ABT-199 (ABT), in the presence of absence of CXCL12 (SDF) and AMD3100 (AMD).

    PCI-32765 purchased from MCE. Usage Cited in: Patent. US 20160222465 A1.

    Impact of Ibrutinib on p-AKT, ERK and BTK expression following SDF-1a stimulation of plenti-GFP vector, CXCR4WT and CXCR4S338X expressing BCWM.1 cells. plenti-GFP vector, CXCR4WT and CXCR4S338X expressing BCWM.1 cells are pretreated for 2 hours with either Ibrutinib (0.5 uM) or AMD3100 (30 uM) prior to stimulation with SDF-1a (20 nM) for 2 minutes. Results depict differences in phospho-AKT, phospho-ERK, and phospho-BTK obtained by immunoblotting follow

    PCI-32765 purchased from MCE. Usage Cited in: Patent. US 20160222465 A1.

    CXCR4S338X expressing BCWM.1 and MWCL-1 cells show variable resistance to PARP and caspase 3 cleavage mediated by WM relevant therapeutics in the presence of SDF-1a, and reversed by AMD3100. plenti-GFP vector, CXCR4WT and CXCR4S338X expressing WM cells are treated for 6 hours with Bendamustine (BENDA), Fludarabine (FLUDARA), Bortezomib (BORT), and Idelalisib (IDELA) at their EC50 doses in the presence or absence of SDF-1a (20 nM) and/or the CXCR4 recep

    PCI-32765 purchased from MCE. Usage Cited in: Oncotarget. 2016 Oct 25;7(43):69760-69769.

    Ibrutinib and WZ4002 inhibitory effects on EGFRY1068 auto-phosphorylation in the H1975 cell line at different time points by removal of drug after 4 h pretreatment

    PCI-32765 purchased from MCE. Usage Cited in: J Exp Clin Cancer Res. 2017 Sep 25;36(1):132.

    The effects of Ibrutinib on the expression levels of cell cycle-related protein. U87 and U251 cells are treated with Ibrutinib for 12 h. The protein extracts are examined using Western blot analysis with the indicated antibodies.

    PCI-32765 purchased from MCE. Usage Cited in: Blood. 2016 Jun 23;127(25):3237-52.

    Ibrutinib binds to the ATP-binding pocketof HCK and blocks ATP binding. Results from kinase active-site inhibition assaysutilizing an ATP-BTN probe that is used to pull downactive kinases in the presence of Ibrutinib, CC-292, or A419259 in lysates from BCWM.1 WM cells.

    PCI-32765 purchased from MCE. Usage Cited in: Signal Transduction and Targeted Therapy. 27 October 2017.

    BTK inhibitors suppress phosphorylation of STAT3 in JVM-3 cells and CLL patient cells. Cells are treated with varying concentrations of Ibrutinib for indicated time periods and western blotting is performed.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    PCI-32765 is a selective, irreversible Btk inhibitor with IC50 value of 0.5 nM.

    IC50 & Target

    IC50: 0.5 nM (Btk)

    In Vitro

    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)[1]. PCI-32765 inhibits BCR-activated primary B cell proliferation (IC50=8 nM). Following FcγR stimulation, PCI-32765 inhibits TNFα, IL-1β and IL-6 production in primary monocytes (IC50=2.6, 0.5, 3.9 nM, respectively)[3].

    In Vivo

    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. PCI-32765 inhibits autoantibody production and the development of kidney disease in the MRL-Fas(lpr) lupus model. PCI-32765 (3.125-50 mg/kg, p.o.) reduces renal disease and autoantibody production in MRL-Fas(lpr) mice[1]. 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[2]. PCI-32765 dose-dependently and potently reverses arthritic inflammation in a therapeutic CIA model with an ED50 of 2.6 mg/kg/day. PCI-32765 also prevents clinical arthritis in CAIA models[3].

    Clinical Trial
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    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 2.2701 mL 11.3507 mL 22.7015 mL
    5 mM 0.4540 mL 2.2701 mL 4.5403 mL
    10 mM 0.2270 mL 1.1351 mL 2.2701 mL
    Please refer to the solubility information to select the appropriate solvent.
    Cell Assay
    [3]

    PCI-32765 is dissolved in DMSO.

    Primary human B cells are isolated from peripheral blood mononuclear cell of healthy human volunteers by Ficoll-Hypaque gradient separation followed by negative selection using human Miltenyl human B cell Isolation Kit II. In 0.2 mL RPMI plus 10% FBS, 100,000 B cells are treated with PCI-32765 (0.3 nM-10 μM) in triplicate wells or vehicle control in 0.1% DMSO final concentration for 30 minutes at 37°C, 5% CO2, then cells are stimulated with 10 μg/mL anti-IgM F(ab')2, 5 μg/mL anti-CD3/CD28 as a negative control or 0.5 μg/mL PMA (Phorbal 12-myristate 13-acetate) as a positive control. B cells are stimulated for 72 hours at 37°C, 5% CO2. Proliferation is measured with Cell Titer Glo reagent and measured on a luminometer. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [3]

    CI-32765 is formulated in 1% methylcellulose, 0.4% Cremephor® EL, and 98.09% water.

    Male DBA1/1OlaHsd mice are injected on days 0 and 21 with Freunds' Complete Adjuvant containing bovine type II collagen. On days 21 to 35, mice are randomized into treatment groups when the average clinical score of each animal is 1.5 (in a scale of 5). PCI-32765 treatment (1.56-12.5 mg/kg, p.o.) is initiated following enrollment and continues for 18 days. Clinical scores are given to each mouse daily for each paw. Clinical score assessment is made using the following criteria: 0=normal; 1=one hind paw or fore paw joint affected or minimal diffuse erythema and swelling; 2=two hind or fore paw joints affected or mild diffuse erythema and swelling; 3=three hind or fore paw joints affected or moderate diffuse erythema and swelling; 4=marked diffuse erythema and swelling or four digit joints affected; 5=severe diffuse erythema and severe swelling of entire paw, unable to flex digits. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References

    Purity: 99.87% ee.: 99.50%

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    Product Name:
    PCI-32765
    Cat. No.:
    HY-10997
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