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PCI-32765 (Ibrutinib)
Bruton's tyrosine kinase (BTK) inhibitor

PCI-32765 (Ibrutinib)

Catalog No. A3001
Size Price Stock Qty
Evaluation Sample $28.00 In stock
5mg $50.00 In stock
10mg $80.00 In stock
50mg $180.00 In stock
200mg $450.00 In stock

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Sample solution is provided at 25 µL, 10mM.

Quality Control

Chemical structure

PCI-32765 (Ibrutinib)

Related Biological Data

PCI-32765
In the Burkitt lymphoma cell line Namalwa, the anti-IgM–induced phosphorylation of protein kinase B (PKB/AKT) and ERK were inhibited by PCI-32765 , whereas phosphorylation of the activating LYN/SYK substrate site Y551 of BTK was actually upregulated.

Review (University of Minnesota)

PCI-32765
Fura-2 loaded purified basophils were incubated with vehicle control (0.0005% DMSO) or 50 nM PCI-32765 for 10 minutes prior to the addition of 0.5 μg/ml anti-IgE antibody and the cytosolic calcium response monitored. The 350/380 excitation ratio is plotted for the average of two experiments.

Review (Thomas Jefferson University)

PCI-32765
Src expression in BMMs cultured with RANKL and M-CSF for 3 days in the presence of ibrutinib at indicated concentration.

Biological Activity

Description Ibrutinib is a potent and highly selective inhibitor of Btk with IC50 of 0.5 nM, modestly potent to Bmx, CSK, FGR, BRK, HCK, less potent to EGFR, Yes, ErbB2, JAK3, etc.
Targets Btk          
IC50 0.5 nM          

Protocol

Cell experiment:

Cell lines

CLL cell lines

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reacting condition

24 h,48 h and 72 h; 1 μM.

Applications

Anti-IgM–supported CLL cell viability was reduced in the presence of PCI-32765 from 69% to 33% at 24 hours, and to 31% and 29% after 48 and 72 hours, respectively. Anti-IgM stimulation induced an average 27%±12% increase in viability after 24 hours compared with unstimulated controls. Preincubation with 1 μM PCI-32765 before anti-IgM stimulation significantly reduced CLL cell viability to 98%±8% of unstimulated controls. Survival signals from NLCs were also effectively inhibited by PCI-32765.

Animal experiment:

Animal models

CB17 SCID mice and Eμ-TCL1 transgenic (Tg) mice on a C3H/BL6 background

Dosage form

Suboptimal (2.5 mg/kg/d); optimal (25 mg/kg/d)

Application

In the adoptive transfer TCL1 mouse model, animals treated PCI-32765 at 2 weeks post cell transfer with the suboptimal (2.5 mg/kg/d) and optimal (25 mg/kg/d) doses exhibited a transient lymphocytosis at day 4, with an average of 7- and 10-fold increases in circulating TCL1 leukemia cells, respectively.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Ponader S, Chen S S, Buggy J J, et al. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo[J]. Blood, 2012, 119(5): 1182-1189.

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Chemical Properties

Cas No. 936563-96-1 SDF Download SDF
Synonyms PCI-32765,Ibrutinib,CRA-032765
Chemical Name 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide
Canonical SMILES C=CC(=O)N1CCCC(C1)N2C3=C(C(=N2)C4=CC=C(C=C4)OC5=CC=CC=C5)C(=NC=N3)N
Formula C25H24N6O2 M.Wt 440.5
Solubility Soluble in DMSO > 10 mM Storage Desiccate at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

Research Update

1. Ibrutinib (PCI-32765) in chronic lymphocytic leukemia. Hematol Oncol Clin North Am. 2013 Aug;27(4):851-60, x. doi: 10.1016/j.hoc.2013.01.006.
Abstract
PCI-32765, an inhibitor of Bruton tyrosine kinase, has the potential to be an integral component of CLL therapy for its inhibition against CLL cell survival and proliferation and its impacts on CLL cell migration and homing.
2. [Effect of PCI-32765 and bortezomib on proliferation and apoptosis of B-cell tumor cell lines and its mechanisms]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013 Oct;21(5):1178-82. doi: 10.7534/j.issn.1009-2137.2013.05.018.
Abstract
PCI-32765, a Btk inhibitor, dose- and time- dependently inhibited proliferation and significantly induced apoptosis in Raji and Ramos cells; while the combination of PCI-32765 and bortezomib synergistically enhanced those effects with down-regulation of Btk, NFKB, Bcl-cl and c-IAP1 and up-regulation of caspase-3.
3. The Bruton tyrosine kinase (BTK) inhibitor PCI-32765 synergistically increases proteasome inhibitor activity in diffuse large-B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells sensitive or resistant to bortezomib. Br J Haematol. 2013 Apr;161(1):43-56. doi: 10.1111/bjh.12206. Epub 2013 Jan 30.
Abstract
The combination of PCI-32765 and bortezomib increased mitochondrial injury, apoptosis and ROS generation in DLBCL and MCL cells with minimal toxicity towards normal CD34(+) bone marrow cells.
4. The orally available Btk inhibitor ibrutinib (PCI-32765) protects against osteoclast-mediated bone loss. Bone. 2014 Mar;60:8-15. doi: 10.1016/j.bone.2013.11.025. Epub 2013 Dec 4.
Abstract
PCI-32765 inhibits both osteoclast differentiation and function leading to suppressed osteoclastic bone resorption, where it downregulates NFATc1 expression and disrupts the actin ring formation in mature osteoclasts. PCI-32765 also alleviated bone loss in an osteoporosis mouse model.

Background

PCI-32765, also named as Ibrutinib, is a Bruton tyrosine kinase inhibitor which is used to study the biological effects of Bruton tyrosine kinase inhibition on mature B-cell function and the progression of B cell-associated diseases in vivo. The Bruton tyrosine kinase is specifically necessary for BCR signaling as demonstrated by human and mouse mutations that disrupt Bruton tyrosine kinase function and prevent B-cell maturation at steps which need a functional BCR pathway. PCI-32765 also inhibited autoantibody production. Occupancy of the Bruton tyrosine kinase active site by PCI-32765 was monitored in vitro and in vivo using a fluorescent affinity probe for Bruton tyrosine kinase.

Reference

Lee A. Honigberga, Ashley M. Smitha, Mint Sirisawada, Erik Vernera, David Lourya, Betty Changa, Shyr Lib, Zhengying Panb,d, Douglas H. Thamme, Richard A. Millera, and Joseph J. Buggya. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. PNAS. 2010; 107(29): 13075 – 80.