生物活性

• 描述Bruton's tyrosine kinase (BTK), a member of the Tec family of tyrosine kinases and expressed in B cells, macrophages, and monocytes but not in T cells, plays a crucial role in signaling through the B cell receptor (BCR) and the Fcγ receptor (FcγR) in B cells and myeloid cells, respectively ^[1]. Vecabrutinib is a potent, noncovalent BTK and ITK (interleukin-2-inducible kinase) inhibitor, with K_d of 0.3 nM and 2.2 nM, respectively. It inhibits WT and C481S BTK with IC₅₀s of 2.9 nM and 4.4 nM, respectively. Vecabrutinib decreases viability of primary CLL cells in the presence of HS5 stromal protection by 5.5%. Vecabrutinib has good oral bioavailability in rat and dog (%F ≥ 40%) and a terminal half-life of 5 to 6 hours and is well tolerated with continuous drug levels.
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03037645	Chronic Lymphocytic Leukemia ... more >> Small Lymphocytic Lymphoma Lymphoplasmacytoid Lymphoma Mantle-Cell Lymphoma Waldenstrom Macroglobulinemia Diffuse Large B Cell Lymphoma Follicular Lymphoma Collapse <<	Phase 1 Phase 2	Recruiting	June 30, 2021	United States, California ... more >> University of California Irvine Medical Center Recruiting Orange, California, United States, 92868-3201 Contact: General Contact    877-827-8839    ucstudy@uci.edu    UC San Diego Moores Cancer Center Recruiting San Diego, California, United States, 92093 Contact: Barbara Ivers    858-822-6281    bivers@ucsd.edu    United States, Florida Moffitt Cancer Center and Research Institute Recruiting Tampa, Florida, United States, 33612 Contact: Natalie Miller    813-745-2591    Natalie.Miller@moffitt.org    United States, Massachusetts Dana-Farber Cancer Institute Recruiting Boston, Massachusetts, United States, 02215 Contact: Conner Shaughnessy    617-582-8437    Conner_Shaughnessy@dfci.harvard.edu    United States, New York Memorial Sloan Kettering Cancer Center Recruiting New York, New York, United States, 10065 Contact: Isaac Deonarine    646-888-1319    deonarii@mskcc.org    Weill Cornell Medicine Recruiting New York, New York, United States, 10065 Contact: Jessica Harper    646-962-9414    jah2070@med.cornell.edu    United States, Texas MD Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Contact: Chongjuan Wei    713-792-3530    cwei@mdanderson.org    United States, Washington Swedish Cancer Institute Recruiting Seattle, Washington, United States, 98104 Contact: Ngan Trinh    206-215-2363    Ngan.Trinh@Swedish.org Collapse <<

• 参考文献

• [1] Caldwell RD, Qiu H, Askew BC, Bender AT, Brugger N, Camps M, Dhanabal M, Dutt V, Eichhorn T, Gardberg AS, Goutopoulos A, Grenningloh R, Head J, Healey B, Hodous BL, Huck BR, Johnson TL, Jones C, Jones RC, Mochalkin I, Morandi F, Nguyen N, Meyring M, Potnick JR, Santos DC, Schmidt R, Sherer B, Shutes A, Urbahns K, Follis AV, Wegener AA, Zimmerli SC, Liu-Bujalski L. Discovery of Evobrutinib: An Oral, Potent, and Highly Selective, Covalent Bruton's Tyrosine Kinase (BTK) Inhibitor for the Treatment of Immunological Diseases. J Med Chem. 2019 Sep 12;62(17):7643-7655. doi: 10.1021/acs.jmedchem.9b00794. Epub 2019 Aug 15. PMID: 31368705.