Target Information
| Target General Information | Top | |||||
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| Target ID |
T25005
(Former ID: TTDR00233)
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| Target Name |
Tyrosine-protein kinase BTK (ATK)
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| Synonyms |
Bruton's tyrosine kinase; Bruton tyrosine kinase; BPK; B-cell progenitor kinase; B cell progenitor kinase; Agammaglobulinemia tyrosine kinase; Agammaglobulinaemia tyrosine kinase; AGMX1
Click to Show/Hide
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| Gene Name |
BTK
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Malignant haematopoietic neoplasm [ICD-11: 2B33] | |||||
| 2 | Mature B-cell lymphoma [ICD-11: 2A85] | |||||
| Function |
Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members. PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK. BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways. Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway. The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense. Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells. Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation. BTK plays also a critical role in transcription regulation. Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes. BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B. Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR. GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression. ARID3A and NFAT are other transcriptional target of BTK. BTK is required for the formation of functional ARID3A DNA-binding complexes. There is however no evidence that BTK itself binds directly to DNA. BTK has a dual role in the regulation of apoptosis. Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.10.2
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| Sequence |
MAAVILESIFLKRSQQKKKTSPLNFKKRLFLLTVHKLSYYEYDFERGRRGSKKGSIDVEK
ITCVETVVPEKNPPPERQIPRRGEESSEMEQISIIERFPYPFQVVYDEGPLYVFSPTEEL RKRWIHQLKNVIRYNSDLVQKYHPCFWIDGQYLCCSQTAKNAMGCQILENRNGSLKPGSS HRKTKKPLPPTPEEDQILKKPLPPEPAAAPVSTSELKKVVALYDYMPMNANDLQLRKGDE YFILEESNLPWWRARDKNGQEGYIPSNYVTEAEDSIEMYEWYSKHMTRSQAEQLLKQEGK EGGFIVRDSSKAGKYTVSVFAKSTGDPQGVIRHYVVCSTPQSQYYLAEKHLFSTIPELIN YHQHNSAGLISRLKYPVSQQNKNAPSTAGLGYGSWEIDPKDLTFLKELGTGQFGVVKYGK WRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANG CLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDF GLSRYVLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYER FTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFKILLSNILDVMDEES Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T58FWN | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
| 1 | Acalabrutinib | Drug Info | Approved | Mantle cell lymphoma | [4] | |
| 2 | Ibrutinib | Drug Info | Approved | Mantle cell lymphoma | [5], [6], [7] | |
| Clinical Trial Drug(s) | [+] 14 Clinical Trial Drugs | + | ||||
| 1 | GDC-0853 | Drug Info | Phase 3 | Multiple sclerosis | [10] | |
| 2 | ARQ 531 | Drug Info | Phase 2 | Hematologic tumour | [14] | |
| 3 | BGB-3112 | Drug Info | Phase 2 | Follicular lymphoma | [15] | |
| 4 | BMS-986142 | Drug Info | Phase 2 | Rheumatoid arthritis | [16] | |
| 5 | CC-292 | Drug Info | Phase 2 | Chronic lymphocytic leukaemia | [17] | |
| 6 | GS-4059 | Drug Info | Phase 2 | B-cell lymphoma | [15] | |
| 7 | LOU064 | Drug Info | Phase 2 | Chronic idiopathic urticaria | [18] | |
| 8 | M2951 | Drug Info | Phase 2 | Multiple sclerosis | [19] | |
| 9 | PRN1008 | Drug Info | Phase 2 | Pemphigus vulgaris | [16], [18] | |
| 10 | AC0058TA | Drug Info | Phase 1 | Autoimmune disease | [16] | |
| 11 | BGB-3113 | Drug Info | Phase 1 | B-cell lymphoma | [15] | |
| 12 | M7583 | Drug Info | Phase 1 | Haematological malignancy | [15] | |
| 13 | ONO-4059 | Drug Info | Phase 1 | B-cell lymphoma | [31] | |
| 14 | PRN2246 | Drug Info | Phase 1 | Multiple sclerosis | [19] | |
| Patented Agent(s) | [+] 1 Patented Agents | + | ||||
| 1 | Pyrrolo[2,3-d]pyrimidine derivative 16 | Drug Info | Patented | Solid tumour/cancer | [32] | |
| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | PCI-45292 | Drug Info | Preclinical | Autoimmune diabetes | [33] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | GDC-0834 | Drug Info | Terminated | Rheumatoid arthritis | [34] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 45 Inhibitor drugs | + | ||||
| 1 | Acalabrutinib | Drug Info | [4] | |||
| 2 | Ibrutinib | Drug Info | [35] | |||
| 3 | GDC-0853 | Drug Info | [16] | |||
| 4 | ARQ 531 | Drug Info | [15] | |||
| 5 | BGB-3112 | Drug Info | [15] | |||
| 6 | BMS-986142 | Drug Info | [16] | |||
| 7 | GS-4059 | Drug Info | [15], [16] | |||
| 8 | LOU064 | Drug Info | [18] | |||
| 9 | M2951 | Drug Info | [16], [19] | |||
| 10 | PRN1008 | Drug Info | [16], [18] | |||
| 11 | AC0058TA | Drug Info | [16] | |||
| 12 | BGB-3113 | Drug Info | [15] | |||
| 13 | M7583 | Drug Info | [15] | |||
| 14 | PRN2246 | Drug Info | [19] | |||
| 15 | Imidazopyridine derivative 4 | Drug Info | [37] | |||
| 16 | PMID27774824-Compound-Figure12Example1 | Drug Info | [37] | |||
| 17 | PMID27774824-Compound-Figure12Example61 | Drug Info | [37] | |||
| 18 | Pyrazolo[4,3-c]pyridine derivative 2 | Drug Info | [37] | |||
| 19 | Pyrrolo[2,3-d]pyrimidine derivative 12 | Drug Info | [32] | |||
| 20 | Pyrrolo[2,3-d]pyrimidine derivative 13 | Drug Info | [32] | |||
| 21 | Pyrrolo[2,3-d]pyrimidine derivative 14 | Drug Info | [32] | |||
| 22 | Pyrrolo[2,3-d]pyrimidine derivative 15 | Drug Info | [32] | |||
| 23 | Pyrrolo[2,3-d]pyrimidine derivative 16 | Drug Info | [32] | |||
| 24 | Pyrrolo[2,3-d]pyrimidine derivative 19 | Drug Info | [32] | |||
| 25 | Pyrrolo[2,3-d]pyrimidine derivative 20 | Drug Info | [32] | |||
| 26 | Pyrrolo[2,3-d]pyrimidine derivative 21 | Drug Info | [32] | |||
| 27 | Pyrrolo[2,3-d]pyrimidine derivative 22 | Drug Info | [32] | |||
| 28 | Pyrrolo[2,3-d]pyrimidine derivative 23 | Drug Info | [32] | |||
| 29 | Pyrrolo[2,3-d]pyrimidine derivative 25 | Drug Info | [32] | |||
| 30 | Pyrrolo[2,3-d]pyrimidine derivative 26 | Drug Info | [32] | |||
| 31 | Pyrrolo[2,3-d]pyrimidine derivative 27 | Drug Info | [32] | |||
| 32 | Pyrrolo[2,3-d]pyrimidine derivative 28 | Drug Info | [32] | |||
| 33 | Pyrrolo[2,3-d]pyrimidine derivative 29 | Drug Info | [32] | |||
| 34 | Pyrrolo[2,3-d]pyrimidine derivative 30 | Drug Info | [32] | |||
| 35 | Pyrrolo[2,3-d]pyrimidine derivative 32 | Drug Info | [32] | |||
| 36 | Pyrrolo[2,3-d]pyrimidine derivative 33 | Drug Info | [32] | |||
| 37 | PCI-45292 | Drug Info | [38] | |||
| 38 | GDC-0834 | Drug Info | [34] | |||
| 39 | CGI-1316 | Drug Info | [35] | |||
| 40 | Inositol 1,3,4,5-Tetrakisphosphate | Drug Info | [39] | |||
| 41 | LFM-A13 | Drug Info | [40] | |||
| 42 | PMID24900538C2c | Drug Info | [41] | |||
| 43 | PMID24915291C31 | Drug Info | [42] | |||
| 44 | PMID24915291C38 | Drug Info | [42] | |||
| 45 | RN486 | Drug Info | [43] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | CC-292 | Drug Info | [17] | |||
| 2 | ONO-4059 | Drug Info | [36] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Dasatinib | Ligand Info | |||||
| Structure Description | Structures of human Bruton's tyrosine kinase in active and inactive conformations suggests a mechanism of activation for TEC family kinases. | PDB:3K54 | ||||
| Method | X-ray diffraction | Resolution | 1.94 Å | Mutation | Yes | [44] |
| PDB Sequence |
YGSWEIDPKD
401 LTFLKELGTG411 QFGVVKYGKW421 RGQYDVAIKM431 IKEFIEEAKV448 MMNLSHEKLV 458 QLYGVCTKQR468 PIFIITEYMA478 NGCLLNYLRE488 MRHRFQTQQL498 LEMCKDVCEA 508 MEYLESKQFL518 HRDLAARNCL528 VNDQGVVKVS538 DFGFPVRWSP565 PEVLMYSKFS 575 SKSDIWAFGV585 LMWEIYSLGK595 MPYERFTNSE605 TAEHIAQGLR615 LYRPHLASEK 625 VYTIMYSCWH635 EKADERPTFK645 ILLSNILDVM655 DEE
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LEU408
3.772
GLY409
4.796
PHE413
4.135
VAL416
4.088
ALA428
3.367
ILE429
4.025
LYS430
3.495
GLU445
3.320
MET449
3.940
VAL458
3.717
ILE472
3.599
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Ibrutinib | Ligand Info | |||||
| Structure Description | BTK1 SOAKED WITH IBRUTINIB-Rev | PDB:5P9I | ||||
| Method | X-ray diffraction | Resolution | 1.11 Å | Mutation | No | [45] |
| PDB Sequence |
GLGYGSWEID
398 PKDLTFLKEL408 GTGQFGVVKY418 GKWRGQYDVA428 IKMIKEGSMS438 EDEFIEEAKV 448 MMNLSHEKLV458 QLYGVCTKQR468 PIFIITEYMA478 NGCLLNYLRE488 MRHRFQTQQL 498 LEMCKDVCEA508 MEYLESKQFL518 HRDLAARNCL528 VNDQGVVKVS538 DFGLSRYVLD 548 DEYTSSVGSK558 FPVRWSPPEV568 LMYSKFSSKS578 DIWAFGVLMW588 EIYSLGKMPY 598 ERFTNSETAE608 HIAQGLRLYR618 PHLASEKVYT628 IMYSCWHEKA638 DERPTFKILL 648 SNILDVMDEE658 S
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LEU408
3.579
GLY409
4.000
THR410
3.926
GLY411
3.851
VAL416
3.729
ALA428
3.263
LYS430
3.249
MET449
3.466
VAL458
4.075
ILE472
3.959
THR474
3.342
GLU475
2.858
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| NF-kappa B signaling pathway | hsa04064 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Osteoclast differentiation | hsa04380 | Affiliated Target |
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| Class: Organismal Systems => Development and regeneration | Pathway Hierarchy | ||
| Platelet activation | hsa04611 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| B cell receptor signaling pathway | hsa04662 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Fc epsilon RI signaling pathway | hsa04664 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Degree | 19 | Degree centrality | 2.04E-03 | Betweenness centrality | 7.89E-04 |
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| Closeness centrality | 2.25E-01 | Radiality | 1.40E+01 | Clustering coefficient | 2.22E-01 |
| Neighborhood connectivity | 3.07E+01 | Topological coefficient | 9.41E-02 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Drug Resistance Mutation (DRM) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Ibrutinib (PCI-32765), the first BTK (Bruton's tyrosine kinase) inhibitor in clinical trials. Curr Hematol Malig Rep. 2013 Mar;8(1):1-6. | |||||
| REF 2 | FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 216059. | |||||
| REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019 | |||||
| REF 4 | 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85. | |||||
| REF 5 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6912). | |||||
| REF 6 | Janssen's IMBRUVICA (ibrutinib) Receives Additional European Commission Approval for the Treatment of Waldenstrom's Macroglobulinemia. Janssen-Cilag International NV (Janssen). Jul 10, 2015. | |||||
| REF 7 | ClinicalTrials.gov (NCT01833039) An Open Label Treatment Use Protocol for Ibrutinib in Subjects With Relapsed or Refractory Mantle Cell Lymphoma. U.S. National Institutes of Health. | |||||
| REF 8 | ClinicalTrials.gov (NCT04578613) ICP-022 Versus Chlorambucil Combined With Rituximab in the Treatment of Untreated CLL/SLL. U.S. National Institutes of Health. | |||||
| REF 9 | ClinicalTrials.gov (NCT04411641) A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing SAR442168 to Placebo in Participants With Nonrelapsing Secondary Progressive Multiple Sclerosis. U.S.National Institutes of Health. | |||||
| REF 10 | ClinicalTrials.gov (NCT04586023) Study To Evaluate The Efficacy And Safety Of Fenebrutinib Compared With Teriflunomide In Relapsing Multiple Sclerosis (RMS) (FENhance). U.S. National Institutes of Health. | |||||
| REF 11 | ClinicalTrials.gov (NCT04305444) Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin's Lymphomas. U.S. National Institutes of Health. | |||||
| REF 12 | ClinicalTrials.gov (NCT04186871) A Randomized, Placebo-Controlled, Double-Blind, Multicenter Study to Assess the Efficacy and Safety of Branebrutinib Treatment in Subjects With Active Systemic Lupus Erythematosus or Primary Sj?gren's Syndrome, or Branebrutinib Treatment Followed by Open-label Abatacept Treatment in Subjects With Active Rheumatoid Arthritis. U.S.National Institutes of Health. | |||||
| REF 13 | ClinicalTrials.gov (NCT04992546) A Randomized, Intra-patient, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Topically Administered PRN473 (SAR444727) in Patients With Mild to Moderate Atopic Dermatitis. U.S.National Institutes of Health. | |||||
| REF 14 | ClinicalTrials.gov (NCT04728893) Efficacy and Safety of MK-1026 in Participants With Hematologic Malignancies (MK-1026-003). U.S. National Institutes of Health. | |||||
| REF 15 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 16 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 17 | Inhibition of Btk with CC-292 provides early pharmacodynamic assessment of activity in mice and humans. J Pharmacol Exp Ther. 2013 Aug;346(2):219-28. | |||||
| REF 18 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 19 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 20 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800040955) | |||||
| REF 21 | ClinicalTrials.gov (NCT04477291) A Study of CG-806 in Patients With Relapsed or Refractory Acute Myeloid Leukemia. U.S. National Institutes of Health. | |||||
| REF 22 | ClinicalTrials.gov (NCT03671590) Study of TG-1701, an Irreversible Bruton's Tyrosine Kinase Inhibitor, in Patients With B-Cell Malignancies. U.S. National Institutes of Health. | |||||
| REF 23 | ClinicalTrials.gov (NCT04210219) A Study of JNJ-64264681 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia. U.S. National Institutes of Health. | |||||
| REF 24 | ClinicalTrials.gov (NCT01765478) Safety,PK/PD, Food Effect Study of Orally Administered HM71224 in Healthy Adult Male Volunteers. U.S. National Institutes of Health. | |||||
| REF 25 | ClinicalTrials.gov (NCT03943056) A Phase 1, Randomized, Blinded, Placebo-Controlled, Single- and Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of BIIB091, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Healthy Adult Participants. U.S.National Institutes of Health. | |||||
| REF 26 | ClinicalTrials.gov (NCT04830137) A Phase 1, Dose Escalation, Safety and Tolerability Study of NX-2127, a Bruton's Tyrosine Kinase (BTK) Degrader, in Adults With Relapsed/Refractory B-cell Malignancies. U.S.National Institutes of Health. | |||||
| REF 27 | ClinicalTrials.gov (NCT05131022) A Phase 1, Dose Escalation, and Cohort Expansion Study Evaluating NX-5948, a Bruton's Tyrosine Kinase (BTK) Degrader, in Adults With Relapsed/Refractory B-cell Malignancies. U.S.National Institutes of Health. | |||||
| REF 28 | ClinicalTrials.gov (NCT05176691) A Multicenter, Open-label, Phase 1 Study Evaluating the Safety and Tolerability of HMPL-760 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Other Non-Hodgkin Lymphoma (NHL). U.S.National Institutes of Health. | |||||
| REF 29 | ClinicalTrials.gov (NCT05294731) A Phase 1, Open-Label, Dose-Escalation and Expansion Study of the Bruton Tyrosine Kinase Targeted Protein-Degrader BGB-16673 in Chinese Patients With B-Cell Malignancies. U.S.National Institutes of Health. | |||||
| REF 30 | ClinicalTrials.gov (NCT05683717) A Phase I, Multicenter, Open Label, and Dose-Escalation Study of TT-01488, Administered Orally in Adult Patients With B-Cell Malignancies. U.S.National Institutes of Health. | |||||
| REF 31 | ClinicalTrials.gov (NCT01659255) Phase I Study of ONO-4059 Given as Monotherapy in Patients With Relapsed/Refractory NHL and CLL. U.S. National Institutes of Health. | |||||
| REF 32 | Pyrrolo[2,3-d]pyrimidines active as Btk inhibitors.Expert Opin Ther Pat. 2017 Dec;27(12):1305-1318. | |||||
| REF 33 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029717) | |||||
| REF 34 | Antiarthritis effect of a novel Bruton's tyrosine kinase (BTK) inhibitor in rat collagen-induced arthritis and mechanism-based pharmacokinetic/pharmacodynamic modeling: relationships between inhibition of BTK phosphorylation and efficacy. J Pharmacol Exp Ther. 2011 Jul;338(1):154-63. | |||||
| REF 35 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1948). | |||||
| REF 36 | ONO-4059, a novel oral Bruton's tyrosine kinase (Btk) inhibitor that demonstrates potent pharmacodynamic activity through Phosphorylated Btk (P-Btk) inhibition, in addition to effective anti-tumour activity in a TMD-8 (DLBCL) xenograft model. Cancer Research. 08/2013; 73(8 Supplement):2452-2452. | |||||
| REF 37 | Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 1.Expert Opin Ther Pat. 2017 Feb;27(2):127-143. | |||||
| REF 38 | Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013 October 10; 122(15): 2539-2549. | |||||
| REF 39 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 40 | A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8. | |||||
| REF 41 | Discovery of Disubstituted Imidazo[4,5-b]pyridines and Purines as Potent TrkA Inhibitors. ACS Med Chem Lett. 2012 Jul 26;3(9):705-9. | |||||
| REF 42 | Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors of Bruton's tyrosine kinase with in vivo antitumor activity. J Med Chem. 2014 Jun 26;57(12):5112-28. | |||||
| REF 43 | RN486, a selective Bruton's tyrosine kinase inhibitor, abrogates immune hypersensitivity responses and arthritis in rodents. J Pharmacol Exp Ther. 2012 Apr;341(1):90-103. | |||||
| REF 44 | Structures of human Bruton's tyrosine kinase in active and inactive conformations suggest a mechanism of activation for TEC family kinases. Protein Sci. 2010 Mar;19(3):429-39. | |||||
| REF 45 | Ability of Bruton's Tyrosine Kinase Inhibitors to Sequester Y551 and Prevent Phosphorylation Determines Potency for Inhibition of Fc Receptor but not B-Cell Receptor Signaling. Mol Pharmacol. 2017 Mar;91(3):208-219. | |||||
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