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PCI-32765

Cat. No. M1825
PCI-32765 Structure
Synonym:

Ibrutinib; CRA-032765

Size Price Availability Quantity
Free Sample (0.5-1 mg)  USD 0 In stock
10mM*1mL in DMSO USD 40  USD40 In stock
5mg USD 35  USD35 In stock
10mg USD 55  USD55 In stock
25mg USD 75  USD75 In stock
50mg USD 110  USD110 In stock
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Quality Control
Biological Activity

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. 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 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. Inhibition of BTK by PCI-32765 overcomes BCR- and chemokine-controlled integrin-mediated retention and homing of malignant B cells in their growth- and survival-supporting lymph node and bone marrow microenvironment, which results in clinically evident CLL regression.

Product Citations
Customer Product Validations & Biological Datas
Source Blood (2011). Figure 3. PCI-32765
Method Western Bolt
Cell Lines CD19+ cells
Concentrations 10 μM
Incubation Time 8 h
Results We found that inhibition of caspase activity by z-VAD-fmk completely prevented the induction of apoptosis provided by PCI-32765 concurrent with a decrease in cleaved PARP expression and a decrease in enzymatic activity of caspase-3
Source Blood (2011). Figure 2. PCI-32765
Method MTT assay
Cell Lines CD19+ cells
Concentrations 10 μM
Incubation Time 12-72 h
Results We found that there were no significant differences in PCI-32765–induced cell death based on interphase cytogenetic analysis
Protocol
Cell Experiment
Cell lines osteoblast cells
Preparation method In vitro osteoblast differentiation Cells derived from calvaria were cultured in an osteogenic medium (50 μM ascorbic acid, 10 nM dexamethasone and 10 mM β- glycerophosphate) in the presence of ibrutinib and subjected to an analysis of the activity of alkaline phosphatase (after 7 days) and bone nodule formation (after 21 days).
Concentrations 0~100nM
Incubation time 7days
Animal Experiment
Animal models RANKL-induced bone loss in mice
Formulation saline
Dosages 6.25, 12.5 or 25 mg/kg 1 h before the first GST-RANKL injection
Administration oral gavage
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information
Molecular Weight 440.5
Formula C25H24N6O2
CAS Number 936563-96-1
Purity 100.00%
Solubility DMSO ≥30 mg/mL
Storage 2-8°C, protect from light, dry, sealed
References

[1] Advani RH, et al. J Clin Oncol. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies.

[2] de Rooij MF, et al. Blood. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia.

[3] Chang BY, et al. Arthritis Res Ther. The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells.

[4] Honigberg LA, et al. Proc Natl Acad Sci U S A. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: PCI-32765, Ibrutinib; CRA-032765 supplier, BTK, inhibitors

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