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Bruton tyrosine kinase

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Target id: 1948

Nomenclature: Bruton tyrosine kinase

Abbreviated Name: Btk

Family: Tec family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 659 Xq22.1 BTK Bruton tyrosine kinase
Mouse - 659 X 56.18 cM Btk Bruton agammaglobulinemia tyrosine kinase
Rat - 660 X q34 Btk Bruton tyrosine kinase
Previous and Unofficial Names Click here for help
AGMX1 | ATK | B-cell progenitor kinase | IMD1 | PSCTK1 | xid | X-linked immune deficiency | Bruton agammaglobulinemia tyrosine kinase
Database Links Click here for help
Alphafold Q06187 (Hs), P35991 (Mm)
BRENDA 2.7.10.2
CATH/Gene3D 2.30.29.30, 3.30.505.10
ChEMBL Target CHEMBL5251 (Hs), CHEMBL3259478 (Mm)
Ensembl Gene ENSG00000010671 (Hs), ENSMUSG00000031264 (Mm), ENSRNOG00000052407 (Rn)
Entrez Gene 695 (Hs), 12229 (Mm), 367901 (Rn)
Human Protein Atlas ENSG00000010671 (Hs)
KEGG Enzyme 2.7.10.2
KEGG Gene hsa:695 (Hs), mmu:12229 (Mm), rno:367901 (Rn)
OMIM 300300 (Hs)
Orphanet ORPHA119094 (Hs)
Pharos Q06187 (Hs)
RefSeq Nucleotide NM_000061 (Hs), NM_013482 (Mm), NM_001007798 (Rn)
RefSeq Protein NP_000052 (Hs), NP_038510 (Mm), NP_001007799 (Rn)
SynPHARM 84961 (in complex with BMS-986142)
81122 (in complex with CGI1746)
83743 (in complex with GDC-0834)
84487 (in complex with ibrutinib)
UniProtKB Q06187 (Hs), P35991 (Mm)
Wikipedia BTK (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  The 1.6 A crystal structure of human bruton's tyrosine kinase bound to a pyrrolopyrimidine-containing compound
PDB Id:  3GEN
Resolution:  1.6Å
Species:  Human
References:  43
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the kinase domain of Bruton's Tyrosine kinase with GDC0834
PDB Id:  4OTF
Ligand:  GDC-0834
Resolution:  1.95Å
Species:  Human
References:  61
Enzyme Reaction Click here for help
EC Number: 2.7.10.2

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BIIB091 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 10.1 pKd 27
⤷ pKd 10.1 (Kd 7x10-11 M) [27]
BIIB068 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.5 pKd 41
⤷ pKd 9.5 (Kd 3x10-10 M) [41]
RN486 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.5 pKd 57
⤷ pKd 9.5 (Kd 3.1x10-10 M) [57]
WZ4002 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pKd 63
⤷ pKd 7.4 (Kd 4.3x10-8 M) [63]
ZYBT1 Small molecule or natural product Click here for species-specific activity table Hs Irreversible inhibition 7.8 pKi 21
⤷ pKi 7.8 (Ki 1.4x10-8 M) [21]
JNJ-64264681 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pKi 50
⤷ pKi 7.3 (Ki 4.85x10-8 M) [50]
PROTAC 23 [PMID: 38321747] Small molecule or natural product Hs Inhibition 6.8 pKi 31
⤷ pKi 6.8 (Ki 1.52x10-7 M) [31]
acalabrutinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition >8.0 pEC50 4
⤷ pEC50 >8.0 (EC50 <1x10-8 M) [4]
luxeptinib Small molecule or natural product Hs Inhibition 10.0 pIC50 26
⤷ pIC50 10.0 (IC50 1x10-10 M) [26]
branebrutinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 10.0 pIC50 39
⤷ pIC50 10.0 (IC50 1.1x10-10 M) [39]
Description: Evaluated in a FLIPR calcium mobilisation assay in Ramos B lymphocytes.
BIIB129 Small molecule or natural product Hs Inhibition 9.5 pIC50 24
⤷ pIC50 9.5 (IC50 3x10-10 M) [24]
sofnobrutinib Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 9.4 pIC50 33
⤷ pIC50 9.4 (IC50 3.9x10-10 M) [33]
Description: Inhibition of unactivated (non-phosphorylated) BTK in vitro.
abivertinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.4 pIC50 58
⤷ pIC50 9.4 (IC50 4x10-10 M) [58]
Description: In a biochemical assay.
spebrutinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition >9.3 pIC50 19
⤷ pIC50 >9.3 (IC50 <5x10-10 M) [19]
BMS-986142 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.3 pIC50 53
⤷ pIC50 9.3 (IC50 5x10-10 M) [53]
BIIB091 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.3 pIC50 27
⤷ pIC50 9.3 (IC50 5x10-10 M) [27]
compound 4g [PMID: 30893553] Small molecule or natural product Hs Inhibition 9.3 pIC50 54
⤷ pIC50 9.3 (IC50 5.2x10-10 M) [54]
Description: Inhibition of recombinant BTK in a biochemical assay
BTK inhibitor 16 [PMID: 30122225] Small molecule or natural product Primary target of this compound Hs Inhibition 9.1 pIC50 46
⤷ pIC50 9.1 (IC50 7x10-10 M) [46]
Description: Using a microfluidic, off-chip mobility shift kinase assay with FITC-AHA-EEPLYWSFPAKKK-NH2 as peptide substrate.
vecabrutinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 9.1 pIC50 28
⤷ pIC50 9.1 (IC50 7.3x10-10 M) [28]
Description: Biochemical assay measuring inhibition of phosphorylation of a fluorescein-labeled polyGAT peptide, in the presence of active BTK enzyme, ATP, and inhibitor.
milrebrutinib Small molecule or natural product Hs Inhibition 9.1 pIC50 32
⤷ pIC50 9.1 (IC50 8.5x10-10 M) [32]
Description: Inhibition of WT BTK
ibrutinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.8 – 9.3 pIC50 10,45
⤷ pIC50 9.3 (IC50 5x10-10 M) [45]
pIC50 8.8 (IC50 1.5x10-9 M) [10]
CNX-774 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition >9.0 pIC50 3
⤷ pIC50 >9.0 (IC50 <1x10-9 M) [3]
remibrutinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 9.0 pIC50 2
⤷ pIC50 9.0 (IC50 1x10-9 M) [2]
Description: Inhibition of hBTK in a biochemical enzyme assay measuring BTK-mediated phosphorylation of a peptide substrate.
BIIB068 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.0 pIC50 41
⤷ pIC50 9.0 (IC50 1x10-9 M) [41]
Description: Biochemical assay measuring enzyme activity inhibition.
ZYBT1 Small molecule or natural product Click here for species-specific activity table Hs Irreversible inhibition 9.0 pIC50 21
⤷ pIC50 9.0 (IC50 1x10-9 M) [21]
compound 71 [WO2018191577A1] Small molecule or natural product Immunopharmacology Ligand Hs Inhibition >9.0 pIC50 29
⤷ pIC50 >9.0 (IC50 <1x10-9 M) [29]
Description: Measuring inhibition of substrate peptide phosphorylation in the presence of active BTK enzyme, ATP, and inhibitor.
rilzabrutinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.8 pIC50 44
⤷ pIC50 8.8 (IC50 1.5x10-9 M) [44]
Description: Measured in a caliper-based kinase assay, to assess inhibition of recombinant human BTK kinase activity (@ 16 μM ATP) using the phosphoacceptor peptide substrate FAM-GEEPLYWSFPAKKK-NH2.
CGI1746 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.7 pIC50 16
⤷ pIC50 8.7 (IC50 1.9x10-9 M) [16]
compound 9 [PMID: 26006010] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.7 pIC50 8
⤷ pIC50 8.7 (IC50 1.9x10-9 M) [8]
compound 36 [PMID: 21958547] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.7 pIC50 34
⤷ pIC50 8.7 (IC50 1.93x10-9 M) [34]
zanubrutinib Small molecule or natural product Approved drug Immunopharmacology Ligand Hs Inhibition 8.7 pIC50 52
⤷ pIC50 8.7 (IC50 2x10-9 M) [52]
Description: Inhibition of the enzymatic activity of recombinant human BTK in a TR-FRET assay.
atuzabrutinib Small molecule or natural product Hs Inhibition 8.7 pIC50 23
⤷ pIC50 8.7 (IC50 2x10-9 M) [23]
Description: Determined in a biochemical enzyme assay measuring inhibition of peptide substrate FAM-GEEPLYWSFPAKKK-NH2 phosphorylation
TAK-020 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition >8.7 pIC50 49
⤷ pIC50 >8.7 (IC50 <1.99x10-9 M) [49]
nemtabrutinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.6 pIC50 47
⤷ pIC50 8.6 (IC50 2.5x10-9 M) [47]
Description: Inhibition of enzyme activity in a biochemical assay
sunvozertinib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 8.5 pIC50 37
⤷ pIC50 8.5 (IC50 2.9x10-9 M) [37]
Description: Inhibition of BTK phosphorylation in Ramos cells (B lymphocyte cell line)
compound 2c [PMID: 24900538] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 51
⤷ pIC50 8.5 (IC50 3.5x10-9 M) [51]
tirabrutinib Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Inhibition 8.4 pIC50 59
⤷ pIC50 8.4 (IC50 4x10-9 M) [59]
compound 38 [PMID: 24915291] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition >8.4 pIC50 35
⤷ pIC50 >8.4 (IC50 <4.4x10-9 M) [35]
compound 31 [PMID: 24915291] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.4 pIC50 35
⤷ pIC50 8.4 (IC50 5x10-9 M) [35]
orelabrutinib Small molecule or natural product Approved drug Immunopharmacology Ligand Hs Inhibition 8.4 pIC50 12
⤷ pIC50 8.4 (IC50 4.4x10-9 M) [12]
Description: Biochemical inhibition determined using a proprietary ADP-Glo kinase assay.
acalabrutinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.3 pIC50 10
⤷ pIC50 8.3 (IC50 5.1x10-9 M) [10]
DD-03-171 Small molecule or natural product Hs Inhibition 8.3 pIC50 17
⤷ pIC50 8.3 (IC50 5.1x10-9 M) [17]
Description: Inhibition of kinase activity in a biochemical assay.
compound 25 [PMID: 31260299] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.3 pIC50 60
⤷ pIC50 8.3 (IC50 5.3x10-9 M) [60]
GDC-0834 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.2 pIC50 61
⤷ pIC50 8.2 (IC50 6x10-9 M) [61]
pirtobrutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.1 – 8.1 pIC50 9
⤷ pIC50 8.1 (IC50 8.6x10-9 M) [9]
Description: Inhibition of autophosphorylation of BTK Y223 in the wild type enzyme stably expressed in HEK293 cells
pIC50 8.1 (IC50 8.8x10-9 M) [9]
Description: Inhibition of autophosphorylation of BTK Y223 in the C481S mutant enzyme stably expressed in HEK293 cells
cinsebrutinib Small molecule or natural product Hs Inhibition >8.0 pIC50 13
⤷ pIC50 >8.0 (IC50 <1x10-8 M) [13]
Description: Pooled value from patent
PRN694 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.8 pIC50 62
⤷ pIC50 7.8 (IC50 1.7x10-8 M) [62]
tolebrutinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 7.7 pIC50 22
⤷ pIC50 7.7 (IC50 2.16x10-8 M) [22]
Description: Determined in a BTK enzymatic activity assay, using proprietary Caliper technology,recombinant human BTK and a phosphoacceptor peptide substrate FAM-GEEPLYWSFPAKKK-NH2.
CHMFL-BTK-11 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Irreversible inhibition 7.6 pIC50 56
⤷ pIC50 7.6 (IC50 2.682x10-8 M) [56]
poseltinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition >7.3 pIC50 11
⤷ pIC50 >7.3 (IC50 <5x10-8 M) [11]
Description: Biochemical assay result. Binned IC50 value provided in patent.
PTD10 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.0 pIC50 36
⤷ pIC50 7.0 (IC50 9.7x10-8 M) [36]
Description: Inhibition of BTK catalytic activity in a cellular assay
evobrutinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition >7.0 pIC50 25
⤷ pIC50 >7.0 (IC50 <1x10-7 M) [25]
Description: Binned value derived from a time-dependent BTK enzyme assay.
elsubrutinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibition >7.0 pIC50 7
⤷ pIC50 >7.0 (IC50 <1x10-7 M) [7]
Description: Inhibition of BTK catalytic domain as measured using TR-FRET based detection of phosphorylated peptide Biotin-(Ahx)-GAEEEIYAAFFA-COOH,
Example A225 [WO2012170976A2] Small molecule or natural product Hs Inhibition >7.0 pIC50 25
⤷ pIC50 >7.0 (IC50 <1x10-7 M) [25]
Description: Enzymatic inhibitio- binned value
PROTAC 23 [PMID: 38321747] Small molecule or natural product Hs Inhibition 6.5 pIC50 31
⤷ pIC50 6.5 (IC50 2.99x10-7 M) [31]
CGI560 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 6.4 pIC50 40
⤷ pIC50 6.4 (IC50 4x10-7 M) [40]
JNJ-64264681 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.3 pIC50 50
⤷ pIC50 6.3 (IC50 5.58x10-7 M) [50]
LFM-A13 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 4.8 pIC50 42
⤷ pIC50 4.8 (IC50 1.72x10-5 M) [42]
Description: IN a cell-free BTK assay using BTK immunoprecipitated from B18.2 cells.
fenebrutinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition - - 14
⤷ [14]
Inhibitor Comments
BI705564 (Boehringer Ingelheim) is a selective, covalent and potent (nM) inhibitor of BTK. It was in early stage clinical stage development, but the first study in patients with systemic lupus erythematosus (NCT03771885) was withdrawn before recruitment began.
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
zelebrudomide Small molecule or natural product Immunopharmacology Ligand Hs Binding 7.7 pKd 48
⤷ pKd 7.7 (Kd 1.8x10-8 M) [48]
Description: Affinity for WT BTK
DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 15,55
Key to terms and symbols Click column headers to sort
Target used in screen: BTK
Ligand Sp. Type Action Value Parameter
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.9 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.3 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.6 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.2 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 7.1 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 6.8 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.7 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx

Reference: 1,20
Key to terms and symbols Click column headers to sort
Target used in screen: BTK/BTK
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 2.1
EGFR/ErbB-2/ErbB-4 inhibitor Small molecule or natural product Hs Inhibitor Inhibition 2.9 47.0 16.0
Lck inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.6 1.0 1.0
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.7
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 2.5 -1.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 8.9 -1.0 -1.0
GSK-3 inhibitor IX Small molecule or natural product Hs Inhibitor Inhibition 13.1 1.0 0.0
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 17.6
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 22.0 10.0 9.0
indirubin derivative E804 Small molecule or natural product Hs Inhibitor Inhibition 24.1 12.0 -2.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [5]. BTK is expressed by all hematopoietic cells, except T cells and differentiated plasma cells.
As BTK is an important mediator of critical B-cell pro-survival mechanisms including apoptosis, cell adhesion, and migration, it has been identified as a drug target for pharmaceutical intervention in B cell malignancies. BTK is the target of several small molecule tyrosine kinase inhibitors, including the approved anti-leukemia drug ibrutinib and several others in the development pipeline.
BTK also plays an essential role in B cell receptor (BCR)-mediated signaling, Fcγ receptor signaling in monocytes, and Fcε receptor signaling in mast cells and basophils. All of these functions have been implicated in the pathophysiology of autoimmune disease, making BTK inhibition a valid strategy for the management of autoimmune diseases. BTK directly interacts with the NLRP3 inflammasome and modifies a number of NLRP3 tyrosine residues, activities that have a significant positive regulatory effect on NLRP3-mediated inflammatory responses [6].
Cell Type Associations
Immuno Cell Type:  B cells
Comment:  BTK is essential for B lymphocyte development, differentiation and signalling, playing an important role in the function of innate immune cells and the adaptive immune response. BTK is involved in cytokine signalling and is a component of the Toll-like receptors (TLR) pathway (linking TLR activation to induction of NF-κB, and downstream cytokine regulation).
References:  18,30
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Agammaglobulinemia, X-linked
Synonyms: Bruton-type agammaglobulinemia [Disease Ontology: DOID:14179]
Disease Ontology: DOID:14179
OMIM: 300755
Orphanet: ORPHA47
Disease:  Isolated growth hormone deficiency, Type III
Synonyms: Short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia
OMIM: 307200
Orphanet: ORPHA632
General Comments
The history, and pros and cons of the various small molecule BTK inhibitor classes that have been developed for clinical applications, and prospects for future drug design are reviewed by Liang et al. (2018) [38].

References

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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]

2. Angst D, Gessier F, Vulpetti A. (2015) Novel amino pyrimidine derivatives. Patent number: WO2015079417A1. Assignee: Novartis Ag. Priority date: 29/11/2013. Publication date: 04/06/2015.

3. Barf T, Kaptein A. (2012) Irreversible protein kinase inhibitors: balancing the benefits and risks. J Med Chem, 55 (14): 6243-62. [PMID:22621397]

4. Barf TA, Jans CGJM, Man PADeA, Oubrie AA, Raaijmakers HCA, Rewinkel JBM, Sterrenburg J-G, Wijkmans JCHM. (2014) 4-imidazopyridazin-1-yl-benzamides and 4-imidazotriazin-1-yl-benzamides as btk inhibitors. Patent number: US20140155385 A1. Assignee: Barf TA, Jans CGJM, Man PADeA, Oubrie AA, Raaijmakers HCA, Rewinkel JBM, Sterrenburg J-G, Wijkmans JCHM. Priority date: 19/07/2011. Publication date: 05/06/2014.

5. Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL. (2005) Tec family kinases in T lymphocyte development and function. Annu Rev Immunol, 23: 549-600. [PMID:15771581]

6. Bittner ZA, Liu X, Mateo Tortola M, Tapia-Abellán A, Shankar S, Andreeva L, Mangan M, Spalinger M, Kalbacher H, Düwell P et al.. (2021) BTK operates a phospho-tyrosine switch to regulate NLRP3 inflammasome activity. J Exp Med, 218 (11). DOI: 10.1084/jem.20201656 [PMID:34554188]

7. Bonafoux D, Davis HM, Frank KE, Friedman MM, Herold JM, Hoemann MZ, Huntley R, Osuma A, Sheppard G, Somal GK et al.. (2014) Primary carboxamides as BTK inhibitors. Patent number: WO2014210255A1. Assignee: Abbvie Inc.. Priority date: 26/06/2013. Publication date: 31/12/2014.

8. Bradshaw JM, McFarland JM, Paavilainen VO, Bisconte A, Tam D, Phan VT, Romanov S, Finkle D, Shu J, Patel V et al.. (2015) Prolonged and tunable residence time using reversible covalent kinase inhibitors. Nat Chem Biol, 11 (7): 525-31. [PMID:26006010]

9. Brandhuber BJ, Brent LT, Eary CT, Kenna A, Khan F, Renshaw VFH, Spencer SR. (2020) Spray-dried dispersions and formulations of (s)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoro propan-2-yl)-1h-pyrazole-4-carboxamide. Patent number: WO2020028258A1. Assignee: Loxo Oncology, Inc.. Priority date: 31/07/2018. Publication date: 06/02/2020.

10. Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR et al.. (2016) Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med, 374 (4): 323-32. [PMID:26641137]

11. Cha MY, Kang SJ, Kim MR, Lee JY, Jeon JY, Jo MG, Kwak EJ, Lee KO, Ha TH, Suh KH, Kim MS. (2011) Novel fused pyrimidine derivatives for inhd3ition of tyrosine kinase activity. Patent number: WO2011162515A2. Assignee: Hanmi Holdings Co. , Ltd.. Priority date: 23/06/2010. Publication date: 29/12/2011.

12. Chen X, Gao Y, Liu C, Ni H, Mulvihill M. (2015) Substituted nicotinimide inhibitors of btk and their preparation and use in the treatment of cancer, inflammation and autoimmune disease. Patent number: WO2015048662A2. Assignee: X-Rx Discovery, Inc.. Priority date: 03/09/2013. Publication date: 02/04/2015.

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How to cite this page

Tec family: Bruton tyrosine kinase. Last modified on 14/08/2024. Accessed on 11/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1948.