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Ibrutinib (PCI-32765)
Ibrutinib (PCI-32765)
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Product Name Ibrutinib (PCI-32765)
Price:
CAS No.: 936563-96-1
Catalog No.: CFN60061
Molecular Formula: C25H24N6O2
Molecular Weight: 440.5 g/mol
Purity: >=98%
Type of Compound: Alkaloids
Physical Desc.: Powder
Source:
Solvent: Chloroform, Dichloromethane, Ethyl Acetate, DMSO, Acetone, etc.
Download: COA    MSDS
Similar structural: Comparison
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Related Screening Libraries
Size /Price /Stock 10 mM * 100 uL in DMSO / Inquiry / In-stock
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Biological Activity
Description: Ibrutinib (PCI-32765) is a potent and highly selective Brutons tyrosine kinase (Btk) inhibitor with IC50 of 0.5 nM in cell-free assays, modestly potent to Bmx, CSK, FGR, BRK, HCK, less potent to EGFR, Yes, ErbB2, JAK3, etc. Ibrutinib is applicable as a Btk ligand in the synthesis of a series of PROTACs including P13I.
Targets: Btk | Bmx | CSK | FGR | BRK
In vitro:
Arthritis Res Ther,2011 Jul 13;13(4):R115.
The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells.[Pubmed: 21752263]
The aim was to determine the effect of the Bruton tyrosine kinase (Btk)-selective inhibitor PCI-32765, currently in Phase I/II studies in lymphoma trials, in arthritis and immune-complex (IC) based animal models and describe the underlying cellular mechanisms.
METHODS AND RESULTS:
PCI-32765 was administered in a series of murine IC disease models including collagen-induced arthritis (CIA), collagen antibody-induced arthritis (CAIA), reversed passive anaphylactic reaction (RPA), and passive cutaneous anaphylaxis (PCA). Clinical and pathologic features characteristic of each model were examined following treatment. PCI-32765 was then examined in assays using immune cells relevant to the pathogenesis of arthritis, and where Btk is thought to play a functional role. These included proliferation and calcium mobilization in B cells, cytokine and chemokine production in monocytes/macrophages, degranulation of mast cells and its subsequent cytokine/chemokine production. PCI-32765 dose-dependently and potently reversed arthritic inflammation in a therapeutic CIA model with an ED(50) of 2.6 mg/kg/day. PCI-32765 also prevented clinical arthritis in CAIA models. In both models, infiltration of monocytes and macrophages into the synovium was completely inhibited and importantly, the bone and cartilage integrity of the joints were preserved. PCI-32765 reduced inflammation in the Arthus and PCA assays. In vitro, PCI-32765 inhibited BCR-activated primary B cell proliferation (IC(50) = 8 nM). Following FcγR stimulation, PCI-32765 inhibited TNFα, IL-1β and IL-6 production in primary monocytes (IC(50) = 2.6, 0.5, 3.9 nM, respectively). Following FcεRI stimulation of cultured human mast cells, PCI-32765 inhibited release of histamine, PGD(2), TNF-α, IL-8 and MCP-1.
CONCLUSIONS:
PCI-32765 is efficacious in CIA, and in IC models that do not depend upon autoantibody production from B cells. Thus PCI-32765 targets not only B lymphocytes but also monocytes, macrophages and mast cells, which are important Btk-expressing effector cells in arthritis.
In vivo:
Blood,2012 Feb 2;119(5):1182-9.
The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo.[Pubmed: 22180443]
B-cell receptor (BCR) signaling is a critical pathway in the pathogenesis of several B-cell malignancies, including chronic lymphocytic leukemia (CLL), and can be targeted by inhibitors of BCR-associated kinases, such as Bruton tyrosine kinase (Btk). PCI-32765, a selective, irreversible Btk inhibitor, is a novel, molecularly targeted agent for patients with B-cell malignancies, and is particularly active in patients with CLL.
METHODS AND RESULTS:
In this study, we analyzed the mechanism of action of PCI-32765 in CLL, using in vitro and in vivo models, and performed correlative studies on specimens from patients receiving therapy with PCI-32765. PCI-32765 significantly inhibited CLL cell survival, DNA synthesis, and migration in response to tissue homing chemokines (CXCL12, CXCL13). PCI-32765 also down-regulated secretion of BCR-dependent chemokines (CCL3, CCL4) by the CLL cells, both in vitro and in vivo. In an adoptive transfer TCL1 mouse model of CLL, PCI-32765 affected disease progression. In this model, PCI-32765 caused a transient early lymphocytosis, and profoundly inhibited CLL progression, as assessed by weight, development, and extent of hepatospenomegaly, and survival.
CONCLUSIONS:
Our data demonstrate that PCI-32765 effectively inhibits CLL cell migration and survival, possibly explaining some of the characteristic clinical activity of this new targeted agent.
Ibrutinib (PCI-32765) Description
Source:
Solvent: Chloroform, Dichloromethane, Ethyl Acetate, DMSO, Acetone, etc.
Storage: Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months(2-8C).

Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20C. Generally, these will be useable for up to two weeks. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.

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Recently, ChemFaces products have been cited in many studies from excellent and top scientific journals

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Calculate Dilution Ratios(Only for Reference)
1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.2701 mL 11.3507 mL 22.7015 mL 45.403 mL 56.7537 mL
5 mM 0.454 mL 2.2701 mL 4.5403 mL 9.0806 mL 11.3507 mL
10 mM 0.227 mL 1.1351 mL 2.2701 mL 4.5403 mL 5.6754 mL
50 mM 0.0454 mL 0.227 mL 0.454 mL 0.9081 mL 1.1351 mL
100 mM 0.0227 mL 0.1135 mL 0.227 mL 0.454 mL 0.5675 mL
* Note: If you are in the process of experiment, it's need to make the dilution ratios of the samples. The dilution data of the sheet for your reference. Normally, it's can get a better solubility within lower of Concentrations.
Protocol
Cell Research:
Blood,2011 Jun 9;117(23):6287-96.
Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765.[Pubmed: 21422473]
Cell lines:Chronic lymphocytic leukemia (CLL) cells
Concentrations: 0.01-100 μM
Incubation Time:  48 hours
Method:
MTT (3'[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assays are performed to determine cytotoxicity. Briefly, cells (CLL B cells or healthy volunteer T cells or NK cells) are incubated for 48 hours with different concentrations of Ibrutinib, or vehicle control. MTT reagent is then added, and plates are incubated for an additional 20 hours before washing with protamine sulfate in phosphate-buffered saline. Dimethyl sulfoxide is added, and absorbance is measured by spectrophotometry at 540 nm in a Labsystems plate reader. Cell viability is also measured at various time points with the use of annexin/PI flow cytometry. Data are analyzed with Expo-ADC32 software package. Results are expressed as the percentage of total positive cells over untreated control. Experiments examining caspase-dependent apoptosis includes the addition of 100μM Z-VAD.
Animal Research:
Proc Natl Acad Sci U S A,2010 Jul 20;107(29):13075-80.
The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy.[Pubmed: 20615965]
Animal Models:MRL-Fas(lpr) lupus model and collagen-induced arthritis model.
Dosages: ≤50 mg/kg
Administration: Administered via p.o.
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