BTK Bruton tyrosine kinase
ENSG00000010671 · protein coding · Open Targets profile
Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling (PubMed:19290921). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (PubMed:19290921). 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 (PubMed:11606584). PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK (PubMed:11606584). BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways (PubMed:16517732, PubMed:17932028). 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 (PubMed:16517732). The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense (PubMed:16517732). Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells (PubMed:16517732, PubMed:17932028). Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation (PubMed:16415872). BTK also plays a critical role in transcription regulation (PubMed:19290921). Induces the activity of NF- kappa-B, which is involved in regulating the expression of hundreds of genes (PubMed:19290921). BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B (PubMed:19290921). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (PubMed:34554188). Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR (PubMed:9012831). GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression (PubMed:9012831). ARID3A and NFAT are other transcriptional target of BTK (PubMed:16738337). BTK is required for the formation of functional ARID3A DNA-binding complexes (PubMed:16738337). There is however no evidence that BTK itself binds directly to DNA (PubMed:16738337). BTK has a dual role in the regulation of apoptosis (PubMed:9751072). Plays a role in STING1- mediated induction of type I interferon (IFN) response by phosphorylating DDX41 (PubMed:25704810). {ECO:0000269|PubMed:11606584, ECO:0000269|PubMed:16415872, ECO:0000269|PubMed:16517732, ECO:0000269|PubMed:16738337, ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:25704810, ECO:0000269|PubMed:34554188, ECO:0000269|PubMed:9012831, ECO:0000303|PubMed:19290921, ECO:0000303|PubMed:9751072}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf, Human Protein Atlas loc
- PROTAC
- Phase 1 Clinical, Literature, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.08708599954843521 (upper bound 0.18310999870300293). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 400 registry trials, updated in the last three years, of the most advanced drugs against BTK (orelabrutinib, ritlecitinib, rilzabrutinib, acalabrutinib, tirabrutinib, pirtobrutinib, zanubrutinib, ibrutinib, abivertinib, evobrutinib, fenebrutinib, elsubrutinib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Luhua (Michael) WangM.D. Anderson Cancer Center · 6 of 6 trials Phase 2+
- Shuhua YiBlood Disease Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, CAMS) · 5 of 5 trials Phase 2+
- Jennifer A WoyachAlliance for Clinical Trials in Oncology · 4 of 4 trials Phase 2+Ph3NCT03737981 · Testing the Addition of a New Anti-cancer Drug, Venetoclax, to the Usual Treatment (Ibrutinib and Obinutuzumab) in Untreated, Older Patients With Chronic Lymphocytic Leukemiabrief
- Nitin JainM.D. Anderson Cancer Center · 4 of 4 trials Phase 2+
- Steven LE GOUILLInstitut Curie · 4 of 4 trials Phase 2+
- Christopher J MelaniECOG-ACRIN Cancer Research Group · 3 of 4 trials Phase 2+
- Barbara EichhorstUniversitätsklinikum Köln · 3 of 3 trials Phase 2+Ph3NCT03836261 · Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLLbrief
- Jan A BurgerM.D. Anderson Cancer Center · 3 of 3 trials Phase 2+
- Kerry A RogersOhio State University Comprehensive Cancer Center · 3 of 3 trials Phase 2+
- Mazyar ShadmanFred Hutch/University of Washington Cancer Consortium · 3 of 3 trials Phase 2+Ph2NCT06839053 · Sonrotoclax, Rituximab, and Zanubrutinib in Treating Participants With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphomabrief
- Toby EyreNCRI UK · 3 of 3 trials Phase 2+
- Christian GrommesMemorial Sloan Kettering Cancer Center · 2 of 3 trials Phase 2+
- Laura S SamplesNational Heart, Lung, and Blood Institute (NHLBI) · 2 of 3 trials Phase 2+Ph2NCT07796373 · Nemtabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) Refractory to Covalent Bruton Tyrosine Kinase Inhibitor or Pirtobrutinib and Previously Treated With a BCL2 Inhibitorbrief
- Preetesh JainM.D. Anderson Cancer Center · 2 of 3 trials Phase 2+Early Ph1NCT05495464 · A Pilot "Window-3" Study of Acalabrutinib Plus Rituximab Followed by Brexucabtagene Autoleucel Therapy in Patients With Previously Untreated High-risk Mantle Cell Lymphomabrief
- Alessandra FerrajoliM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
Registry trials of orelabrutinib, ritlecitinib, rilzabrutinib, acalabrutinib, tirabrutinib, pirtobrutinib, zanubrutinib, ibrutinib, abivertinib, evobrutinib, fenebrutinib, elsubrutinib updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 272 of 392 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 8 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
102 trials of drugs against BTK were stopped early; 6 give no reason
Terminated, withdrawn and suspended interventional trials of orelabrutinib, ritlecitinib, rilzabrutinib, acalabrutinib, tirabrutinib, pirtobrutinib, zanubrutinib, ibrutinib, abivertinib, evobrutinib, fenebrutinib, elsubrutinib, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 102.
- terminated · 2026-05-22 · University of California, San Diego · Ibrutinib 560mg PO daily (Imbruvica)“Lack of scientific process of cancer-related clinical intervention”
- terminated · 2026-05-22 · Mayo Clinic · Ibrutinib“poor accrual”
- terminated · 2026-05-05 · Mayo Clinic · Ibrutinib“Discontinued after interim analysis for futility; no treatment successes observed in the first 12 patients”
- terminated · 2026-04-27 · Xuanwu Hospital, Beijing · zanubrutinib“Difficult in participant recruiting”
- terminated · 2026-03-02 · H. Lee Moffitt Cancer Center and Research Institute · Ibrutinib“Funding unavailable”
- terminated · 2025-12-30 · Mayo Clinic · Ibrutinib“Slow accrual”
- terminated · 2025-12-30 · Swiss Cancer Institute · Ibrutinib“The board decision has been made to conclude the trial ahead of schedule. The primary endpoint has been successfully achieved and published, and funding was secured to support these three years of followup.”
- terminated · 2025-12-15 · M.D. Anderson Cancer Center · Pirtobrutinib“<75% participation”
- withdrawn · 2025-12-09 · Ahuva D Cices · Ritlecitinib“Sponsor terminated study”
- withdrawn · 2025-10-03 · Karyopharm Therapeutics Inc · Ibrutinib“Sponsor decision”
- terminated · 2025-08-17 · Mayo Clinic · Ibrutinib“Drug company decided to not fund the phase 2 portion”
- terminated · 2025-07-18 · Icahn School of Medicine at Mount Sinai · Ritlecitinib“No significant improvement in disease as graded by our assessments.”
- terminated · 2025-07-11 · Pfizer · matched by the registry's drug synonyms“For business reasons”
- terminated · 2025-06-17 · Gilead Sciences · Tirabrutinib“The goal of the study was to improve tolerability while maintaining or increasing efficacy. The results of this study showed no efficacy advantage although the combinations were well tolerated.”
- terminated · 2025-06-12 · Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany · Evobrutinib“Primary analysis of the RMS phase 3 study (MS200527_0080) resulted in the early termination of the study.”
- withdrawn · 2025-06-05 · AstraZeneca · Pirtobrutinib, Acalabrutinib“AstraZeneca has made the decision to cancel the trial.”
- terminated · 2025-05-31 · University of Miami · Acalabrutinib“Investigator Decision”
- withdrawn · 2025-05-22 · Inhye Ahn · Ibrutinib, Acalabrutinib“Bayer is no longer funding due to lack of accrual”
- terminated · 2025-05-16 · Novartis Pharmaceuticals · ibrutinib“Business reasons”
- terminated · 2025-05-14 · EMD Serono Research & Development Institute, Inc. · Evobrutinib“Results from the EVOLUTION clinical trials showed evobrutinib did not meet its primary endpoint of annualized relapse rate for up to 156 weeks compared to oral teriflunomide in both studies.”
- terminated · 2025-05-13 · Memorial Sloan Kettering Cancer Center · Ibrutinib“Lack of accrual”
- suspended · 2025-04-25 · Henan Cancer Hospital · Zanubrutinib“Data in analysis”
- terminated · 2025-04-10 · MingSight Pharmaceuticals, Inc · acalabrutinib“The study is terminated due to major protocol revisions. A new study in CLL patients is planned.”
- terminated · 2025-03-21 · Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany · Evobrutinib“Primary analysis of the RMS phase 3 study (MS200527_0082) resulted in the early termination of the study.”
- terminated · 2025-03-17 · Aprea Therapeutics · APR-246 (eprenetapopt) + Acalabrutinib in CLL, APR-246 (eprenetapopt) 4.5 g/d + (Acalabrutinib, OR, (Venetoclax +Rituximab)), in CLL and/or MCL and/or RT“Sponsor decision”
Paediatric incentives and obligations for BTK's drugs
For orelabrutinib, ritlecitinib, rilzabrutinib, acalabrutinib, tirabrutinib, pirtobrutinib, zanubrutinib, ibrutinib, abivertinib, evobrutinib, fenebrutinib, elsubrutinib: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · BTK is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMA/PE/0000236669 (ritlecitinib, Treatment of vitiligo): PM: decision on the application for modification of an agreed PIP, 14 Apr 2025; EMEA-002451-PIP02-21 (ritlecitinib, Treatment of ulcerative colitis): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 10 Aug 2022; EMEA-002284-PIP01-17 (Evobrutinib, Treatment of multiple sclerosis): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 6 Dec 2012; EMEA-002354-PIP03-24 (zanubrutinib, Treatment of lymphoplasmacytic lymphoma;Treatment of mature B-cell neoplasms (excluding lymphoplasmacytic lymphoma)): W: decision granting a waiver in all age groups for all conditions or indications, 10 Jul 2024; +12 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/16/1625 withdrawn 21 Mar 2016: Treatment of mantle cell lymphoma; EU/3/25/3120 positive 22 Aug 2025: Treatment of immunoglobulin G4-related disease; EU/3/24/3019 positive 16 Jan 2025: Treatment of autoimmune haemolytic anaemia; EU/3/20/2278 positive 4 Jun 2020: Treatment of immune thrombocytopenia; +11 moreRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Wayrilz: authorised since 22 Dec 2025, orphan medicine; Brukinsa: authorised since 22 Nov 2021; Imbruvica: authorised since 21 Oct 2014; Calquence: authorised since 5 Nov 2020; +2 moreRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of orelabrutinib, ritlecitinib, rilzabrutinib, acalabrutinib, tirabrutinib, pirtobrutinib, zanubrutinib, ibrutinib, abivertinib, evobrutinib, fenebrutinib, elsubrutinibRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 43 interventional studies of orelabrutinib, ritlecitinib, rilzabrutinib, acalabrutinib, tirabrutinib, pirtobrutinib, zanubrutinib, ibrutinib, abivertinib, evobrutinib, fenebrutinib, elsubrutinib include patients under 18; 24 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 24 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.