| BTK, AGMX1, AT, ATK, BPK, IMD1, PSCTK1, XLA, Bruton tyrosine kinase|
OMIM: 300300 MGI: 88216 HomoloGene: 30953 GeneCards: BTK
Bruton's tyrosine kinase (abbreviated Btk or BTK) also known as tyrosine-protein kinase BTK is an enzyme that in humans is encoded by the BTK gene. BTK is a kinase that plays a crucial role in B-cell development.
Bruton's tyrosine kinase Wikipedia
BTK plays a crucial role in B cell maturation as well as mast cell activation through the high-affinity IgE receptor.
Btk contains a PH domain that binds phosphatidylinositol (3,4,5)-trisphosphate (PIP3). PIP3 binding induces Btk to phosphorylate phospholipase C, which in turn hydrolyzes PIP2, a phosphatidylinositol, into two second messengers, inositol triphosphate (IP3) and diacylglycerol (DAG), which then go on to modulate the activity of downstream proteins during B-cell signalling.
Mutations in the BTK gene are implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia); sometimes abbreviated to XLA. Patients with XLA have normal pre-B cell populations in their bone marrow but these cells fail to mature and enter the circulation. The Btk gene is located on the X chromosome. At least 400 mutations of the BTK gene have been identified.
Approved drugs that inhibit BTK :Ibrutinib (PCI-32765), a selective Bruton's tyrosine kinase inhibitor.
Various drugs that inhibit BTK are in clinical trials:Phase 3:
Acalabrutinib, for relapsed CLL, 95% overall remission reported.
ONO-4059 for Non-Hodgkin's Lymphoma and/or CLL. Renamed GS-4059 and now in trial NCT02457598.
spebrutinib (AVL-292, CC-292)
BGB-3111 for CLL. It can be taken orally.
Bruton's tyrosine kinase was discovered in 1993 and is named for Ogden Bruton, who first described XLA in 1952.
Bruton's tyrosine kinase has been shown to interact with: