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The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy.
Honigberg LA, Smith AM, Sirisawad M, Verner E, Loury D, Chang B, Li S, Pan Z, Thamm DH, Miller RA, Buggy JJ. Honigberg LA, et al. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13075-80. doi: 10.1073/pnas.1004594107. Epub 2010 Jul 6. Proc Natl Acad Sci U S A. 2010. PMID: 20615965 Free PMC article.
PCI-32765 also inhibited autoantibody production and the development of kidney disease in the MRL-Fas(lpr) lupus model. Occupancy of the Btk active site by PCI-32765 was monitored in vitro and in vivo using a fluorescent affinity probe for Btk. ...
PCI-32765 also inhibited autoantibody production and the development of kidney disease in the MRL-Fas(lpr) lupus model. Occupa
Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies.
Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, Kolibaba KS, Furman RR, Rodriguez S, Chang BY, Sukbuntherng J, Izumi R, Hamdy A, Hedrick E, Fowler NH. Advani RH, et al. J Clin Oncol. 2013 Jan 1;31(1):88-94. doi: 10.1200/JCO.2012.42.7906. Epub 2012 Oct 8. J Clin Oncol. 2013. PMID: 23045577 Free PMC article. Clinical Trial.
PURPOSE: Survival and progression of mature B-cell malignancies depend on signals from the B-cell antigen receptor, and Bruton tyrosine kinase (BTK) is a critical signaling kinase in this pathway. We evaluated ibrutinib (PCI-32765), a small-molecule irreversi …
PURPOSE: Survival and progression of mature B-cell malignancies depend on signals from the B-cell antigen receptor, and Bruton tyrosine kina …
The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo.
Ponader S, Chen SS, Buggy JJ, Balakrishnan K, Gandhi V, Wierda WG, Keating MJ, O'Brien S, Chiorazzi N, Burger JA. Ponader S, et al. Blood. 2012 Feb 2;119(5):1182-9. doi: 10.1182/blood-2011-10-386417. Epub 2011 Dec 16. Blood. 2012. PMID: 22180443 Free PMC article.
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. ...In an adoptive transfer TCL1 mouse model of CLL …
In this study, we analyzed the mechanism of action of PCI-32765 in CLL, using in vitro and in vivo models, and performed corre …
[Effects of PCI-32765 and Dasatinib on the Acute Lymphoblastic Leukemic Cells and Their Mechanisms].
Deng Y, Tao SD, Zhang X, Ma JJ, He ZM, Chen Y, Deng ZK, Yu L. Deng Y, et al. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2017 Feb;25(1):72-79. doi: 10.7534/j.issn.1009-2137.2017.01.012. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2017. PMID: 28245378 Chinese.
PCI-32765 and Dasatinib could decrease the expression and activity of BCR-ABL, Btk, Lyn, Src in Sup-B15 and RS4;11 cells. CONCLUSION: PCI-32765 or Dasatinib can inhibit the proliferation and induce the apoptosis of Sup-B15 and RS4;11 cells, PCI-
PCI-32765 and Dasatinib could decrease the expression and activity of BCR-ABL, Btk, Lyn, Src in Sup-B15 and RS4;11 cells. CONC
The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia.
de Rooij MF, Kuil A, Geest CR, Eldering E, Chang BY, Buggy JJ, Pals ST, Spaargaren M. de Rooij MF, et al. Blood. 2012 Mar 15;119(11):2590-4. doi: 10.1182/blood-2011-11-390989. Epub 2012 Jan 25. Blood. 2012. PMID: 22279054
Furthermore, PCI-32765 also inhibits CXCL12-, CXCL13-, and CCL19-induced signaling, adhesion, and migration of primary CLL cells. Our data indicate that inhibition of BTK by PCI-32765 overcomes BCR- and chemokine-controlled integrin-mediated retention …
Furthermore, PCI-32765 also inhibits CXCL12-, CXCL13-, and CCL19-induced signaling, adhesion, and migration of primary CLL cel …
Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765.
Herman SE, Gordon AL, Hertlein E, Ramanunni A, Zhang X, Jaglowski S, Flynn J, Jones J, Blum KA, Buggy JJ, Hamdy A, Johnson AJ, Byrd JC. Herman SE, et al. Blood. 2011 Jun 9;117(23):6287-96. doi: 10.1182/blood-2011-01-328484. Epub 2011 Mar 21. Blood. 2011. PMID: 21422473 Free PMC article.
No influence of PCI-32765 on T-cell survival is observed. Treatment of CD40 or BCR activated CLL cells with PCI-32765 results in inhibition of BTK tyrosine phosphorylation and also effectively abrogates downstream survival pathways activated by this ki …
No influence of PCI-32765 on T-cell survival is observed. Treatment of CD40 or BCR activated CLL cells with PCI-3276
Ibrutinib (PCI-32765) in chronic lymphocytic leukemia.
Jain N, O'Brien S. Jain N, et al. Hematol Oncol Clin North Am. 2013 Aug;27(4):851-60, x. doi: 10.1016/j.hoc.2013.01.006. Hematol Oncol Clin North Am. 2013. PMID: 23915749 Free PMC article. Review.
Many kinases in the BCR signaling pathway are being studied as potential therapeutic targets. Ibrutinib (PCI-32765) is a novel first-in-class selective inhibitor of Bruton tyrosine kinase. Preclinical evidence suggests that ibrutinib inhibits CLL cell …
Many kinases in the BCR signaling pathway are being studied as potential therapeutic targets. Ibrutinib (PCI-32765) is …
PCI-32765: a novel Bruton's tyrosine kinase inhibitor for the treatment of lymphoid malignancies.
Winer ES, Ingham RR, Castillo JJ. Winer ES, et al. Expert Opin Investig Drugs. 2012 Mar;21(3):355-61. doi: 10.1517/13543784.2012.656199. Epub 2012 Feb 3. Expert Opin Investig Drugs. 2012. PMID: 22300471 Review.
AREAS COVERED: This review will summarize the current knowledge of the Btk pathway and its role in lymphoid malignancies. It will also discuss the present data about PCI-32765 in both the preclinical and clinical setting. EXPERT OPINION: PCI-32765 is a …
AREAS COVERED: This review will summarize the current knowledge of the Btk pathway and its role in lymphoid malignancies. It will also discu …
Targeting BTK in CLL: Beyond Ibrutinib.
Bond DA, Woyach JA. Bond DA, et al. Curr Hematol Malig Rep. 2019 Jun;14(3):197-205. doi: 10.1007/s11899-019-00512-0. Curr Hematol Malig Rep. 2019. PMID: 31028669 Review.
PURPOSE OF REVIEW: While the Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia (CLL), current limitations include off-target toxicities and the development of resistance. ...Early-phase studies are underway …
PURPOSE OF REVIEW: While the Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib has revolutionized the treatment of chronic lymphocy …
Management of adverse effects/toxicity of ibrutinib.
Paydas S. Paydas S. Crit Rev Oncol Hematol. 2019 Apr;136:56-63. doi: 10.1016/j.critrevonc.2019.02.001. Epub 2019 Feb 10. Crit Rev Oncol Hematol. 2019. PMID: 30878129 Review.
Ibrutinib has been approved by FDA for the treatment of mantle cell lymphoma, chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia, marginal zone lymphoma and chronic graft-versus-host disease in allogeneic stem cell transplantation. Ibrutinib is generally
Ibrutinib has been approved by FDA for the treatment of mantle cell lymphoma, chronic lymphocytic leukemia, Waldenstrom's macroglobul
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