MedKoo product information:

  Ibrutinib

Description of Ibrutinib (PCI-32765): Ibrutinib is a BTK inhibitor, is also an orally bioavailable small-molecule inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. BTK inhibitor PCI-32765 binds to and inhibits BTK activity, preventing B-cell activation and B-cell-mediated signaling and inhibiting the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is required for B cell receptor (BCR) signaling, plays a key role in B-cell maturation, and is overexpressed in a number of B-cell malignancies. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer:    Pharmacyclics, Inc.

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. PCI-32765 significantly inhibited CLL cell survival, DNA synthesis, and migration in response to tissue homing chemokines (CXCL12, CXCL13). PCI-32765 also downregulated 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. 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. (source: Blood. 2011 Dec 16. [Epub ahead of print])

1. Methods for assessing expression of SMAD4 gene in identifying pancreatic cancer patients likely to respond to treatment with BTK inhibitors By Han, Haiyong; Von Hoff, Daniel D.; Diep, Caroline H.; Yin, Hongwei From PCT Int. Appl. (2011), WO 2011133609 A2 20111027.

2. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765 By Herman, Sarah E. M.; Gordon, Amber L.; Hertlein, Erin; Ramanunni, Asha; Zhang, Xiaoli; Jaglowski, Samantha; Flynn, Joseph; Jones, Jeffrey; Blum, Kristie A.; Buggy, Joseph J.; et al From Blood (2011), 117(23), 6287-6296.

3. Protein Kinase C Inhibitor Sotrastaurin Selectively Inhibits the Growth of CD79 Mutant Diffuse Large B-Cell Lymphomas By Naylor, Tara L.; Tang, Huaping; Ratsch, Boris A.; Enns, Andreas; Loo, Alice; Chen, Liqing; Lenz, Peter; Waters, Nigel J.; Schuler, Walter; Doerken, Bernd; et al From Cancer Research (2011), 71(7), 2643-2653.

4. Inhibition of IgE-mediated secretion from human basophils with a highly selective Bruton's tyrosine kinase, Btk, inhibitor By MacGlashan, Donald, Jr.; Honigberg, Lee A.; Smith, Ashley; Buggy, Joseph; Schroeder, John T. From International Immunopharmacology (2011), 11(4), 475-479.

5. Inhibitors of Bruton's tyrosine kinase By Honigberg, Lee; Verner, Erik J.; Buggy, Joseph J.; Loury, David J.; Chen, Wei From U.S. Pat. Appl. Publ. (2010), US 20100254905 A1 20101007.

6. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy By Honigberg, Lee A.; Smith, Ashley M.; Sirisawad, Mint; Verner, Erik; Loury, David; Chang, Betty; Li, Shyr; Pan, Zhengying; Thamm, Douglas H.; Miller, Richard A.; et al From Proceedings of the National Academy of Sciences of the United States of America (2010), 107(29), 13075-13080, S13075/1-S13075/3.

7. Preparation of substituted pyrazolopyrimidinamines as inhibitors of Bruton's tyrosine kinase By Honigberg, Lee; Verner, Erik; Buggy, Joseph; Loury, David; Chen, Wei From PCT Int. Appl. (2010), WO 2010009342 A2 20100121.

8. Preparation of substituted pyrazolopyrimidinamines as therapeutic inhibitors of Bruton's tyrosine kinase and other kinases By Honigberg, Lee; Verner, Erik; Buggy, Joseph J.; Loury, David; Chen, Wei From PCT Int. Appl. (2008), WO 2008121742 A2 20081009.

9. Preparation of substituted pyrazolopyrimidinamines as inhibitors of Bruton's tyrosine kinase By Honigberg, Lee; Verner, Erik; Pan, Zhengying From U.S. Pat. Appl. Publ. (2008), US 20080139582 A1 20080612.

10. Preparation of substituted pyrazolopyrimidinamines as inhibitors of Bruton's tyrosine kinase By Honigberg, Lee; Verner, Erik; Pan, Zhengying From U.S. Pat. Appl. Publ. (2008), US 20080108636 A1 20080508.

11. Preparation of 1H-pyrazolo[3,4-d]pyrimidine derivatives as bruton's tyrosine kinase inhibitors By Honigberg, Lee; Verner, Erik; Pan, Zhengying From U.S. Pat. Appl. Publ. (2008), US 20080076921 A1 20080327.

12. Discovery of selective irreversible inhibitors for bruton's tyrosine kinase By Pan, Zhengying; Scheerens, Heleen; Li, Shyr-Jiann; Schultz, Brian E.; Sprengeler, Paul A.; Burrill, L. Chuck; Mendonca, Rohan V.; Sweeney, Michael D.; Scott, Keana C. K.; Grothaus, Paul G.; et al From ChemMedChem (2007), 2(1), 58-61.