BCR BCR activator of RhoGEF and GTPase
ENSG00000186716 · protein coding · Open Targets profile
Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein (GAP) domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form (PubMed:17116687, PubMed:1903516, PubMed:7479768). The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form (PubMed:23940119, PubMed:7479768). The amino terminus contains an intrinsic kinase activity (PubMed:1657398). Functions as an important negative regulator of neuronal RAC1 activity (By similarity). Regulates macrophage functions such as CSF1-directed motility and phagocytosis through the modulation of RAC1 activity (PubMed:17116687). Plays a major role as a RHOA GEF in keratinocytes being involved in focal adhesion formation and keratinocyte differentiation (PubMed:23940119). {ECO:0000250|UniProtKB:Q6PAJ1, ECO:0000269|PubMed:1657398, ECO:0000269|PubMed:17116687, ECO:0000269|PubMed:1903516, ECO:0000269|PubMed:23940119, ECO:0000269|PubMed:7479768}.
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 Withdrawn means the drug was pulled from the market or from development.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, Druggable Family
- Antibody
- GO CC med conf, Human Protein Atlas loc
- PROTAC
- Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.4185900092124939 (upper bound 0.5209100246429443). 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 318 registry trials, updated in the last three years, of the most advanced drugs against BCR (bosutinib, ponatinib, nilotinib hydrochloride monohydrate, bosutinib monohydrate, asciminib, imatinib, dasatinib, nilotinib, olverembatinib, radotinib, vodobatinib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Elias JabbourM.D. Anderson Cancer Center · 9 of 9 trials Phase 2+Ph2NCT03263572 · Blinatumomab, Methotrexate, Cytarabine, and Ponatinib in Treating Patients With Philadelphia Chromosome-Positive, or BCR-ABL Positive, or Relapsed/Refractory, Acute Lymphoblastic Leukemiabrief
- Fadi HaddadUT MD Anderson · 3 of 3 trials Phase 2+
- Farhad Ravandi-KashaniSWOG Cancer Research Network · 3 of 3 trials Phase 2+Ph2NCT00792948 · Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemiabrief
- Fernando L PaganGeorgetown Univeristy · 3 of 3 trials Phase 2+
- Jianxiang WangInstitute of Hematology & Blood Diseases Hospital, China · 2 of 4 trials Phase 2+
- Nicholas ShortM.D. Anderson Cancer Center · 2 of 3 trials Phase 2+Ph1/Ph2NCT06308588 · Phase I/II Study of the Combination of Blinatumomab and Asciminib in Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemiabrief
- Xiaofan ZhuInstitute of Hematology and Blood Diseases Hospital, CAMS & PUMC · 2 of 3 trials Phase 2+
- Anjali S AdvaniSWOG Network Cancer Center · 2 of 2 trials Phase 2+
- Antoine ItalianoInstitut Bergonié · 2 of 2 trials Phase 2+
- Eric LenzeWashington University School of Medicine · 2 of 2 trials Phase 2+
- Fausto Castagnetti"Seragnoli" Institute of Hematology Bologna (Italy) · 2 of 2 trials Phase 2+
- Franck NICOLINIHospices Civils de Lyon · 2 of 2 trials Phase 2+
- Jean-Yves BLAYCentre Leon Berard · 2 of 2 trials Phase 2+
- Jie Jinthe First Affiliated Hospital, College of Medicine · 2 of 2 trials Phase 2+
- Min-Hee RyuAsan Medical Center · 2 of 2 trials Phase 2+
Registry trials of bosutinib, ponatinib, nilotinib hydrochloride monohydrate, bosutinib monohydrate, asciminib, imatinib, dasatinib, nilotinib, olverembatinib, radotinib, vodobatinib 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; 244 of 309 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. 9 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
236 trials of drugs against BCR were stopped early; 23 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of bosutinib, ponatinib, nilotinib hydrochloride monohydrate, bosutinib monohydrate, asciminib, imatinib, dasatinib, nilotinib, olverembatinib, radotinib, vodobatinib, 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 236.
- terminated · 2026-11-04 · City of Hope Medical Center · dasatinib“Terminated early due a shift in resources after lackluster performance of the drug.”
- suspended · 2026-10-01 · Institut Paoli-Calmettes · Dasatinib“Planned interim analyse”
- terminated · 2026-07-13 · Novartis Pharmaceuticals · Nilotinib, Asciminib“Sponsor decision: The primary endpoint of the core/TF1 was achieved, and the sample size of Extension/TFR2 was unlikely to yield meaningful results. No new safety signals were observed. For these reasons, continuing the study was not justified.”
- terminated · 2026-05-29 · Sarit Assouline · Asciminib, Imatinib“Insufficient patient accrual”
- terminated · 2026-05-13 · Sun Pharma Advanced Research Company Limited · Vodobatinib (K0706) capsules“Closed for administrative, non-safety-related reasons.”
- terminated · 2026-04-27 · M.D. Anderson Cancer Center · Ponatinib“< 75% participation”
- terminated · 2026-03-25 · University of Maryland, Baltimore · Imatinib“The Principal Investigator left the institution. The study was halted prematurely.”
- terminated · 2026-03-13 · Centre Oscar Lambret · Imatinib“Study stopped at the end of the first step”
- terminated · 2026-03-02 · M.D. Anderson Cancer Center · Asciminib“75% < Participants, Administrativley Complete”
- terminated · 2026-01-29 · Indiana University · Imatinib Mesylate“low accrual”
- terminated · 2025-12-08 · M.D. Anderson Cancer Center · Ponatinib“Closed due to slow accrual”
- terminated · 2025-10-03 · National Cancer Institute (NCI) · Dasatinib“Other - Poor accrual”
- terminated · 2025-10-02 · Takeda · Ponatinib“Phase 1 enrollment was terminated due to dose-limiting toxicities, thus the study was terminated by Sponsor.”
- terminated · 2025-08-22 · OHSU Knight Cancer Institute · imatinib mesylateNo reason given
- terminated · 2025-06-27 · AHS Cancer Control Alberta · Imatinib Oral Tablet“Lack of Accrual”
- terminated · 2025-06-08 · M.D. Anderson Cancer Center · Dasatinib“Study was closed early due to low accrual and lack of response.”
- terminated · 2025-06-03 · M.D. Anderson Cancer Center · Dasatinib, Imatinib Mesylate, Nilotinib“Per PI Request. 2) No additional benefit was noted with the addition of Ruxolitinib.”
- terminated · 2025-05-08 · M.D. Anderson Cancer Center · Ponatinib Hydrochloride“The study was terminated early due to slow accrual and low level of interest both by the sponsor and by the department”
- withdrawn · 2025-05-01 · Institute of Hematology & Blood Diseases Hospital, China · Dasatinib“No enough eligable participants enrolled”
- terminated · 2025-05-01 · Institute of Hematology & Blood Diseases Hospital, China · Imatinib“terminated”
- terminated · 2025-01-27 · Handok Inc. · matched by the registry's drug synonyms“Change of Development Plan”
- terminated · 2025-01-17 · Gruppo Italiano Malattie EMatologiche dell'Adulto · Ponatinib“low enrollment rate”
- withdrawn · 2024-12-09 · MedPacto, Inc. · Imatinib“Changing trial strategy”
- terminated · 2024-10-10 · Aerovate Therapeutics · matched by the registry's drug synonyms“Results from the parent study (IMPAHCT) demonstrated that while inhaled imatinib was well tolerated, it did not prove to be efficacious at any of the doses of AV-101 evaluated in the study.”
- terminated · 2024-08-23 · Aerovate Therapeutics · matched by the registry's drug synonyms“The IMPAHCT study demonstrated that while inhaled imatinib was well tolerated, it did not prove to be efficacious at any of the doses of AV-101 evaluated in the study.”
Paediatric incentives and obligations for BCR's drugs
For bosutinib, ponatinib, nilotinib hydrochloride monohydrate, bosutinib monohydrate, asciminib, imatinib, dasatinib, nilotinib, olverembatinib, radotinib, vodobatinib: 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 · BCR 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/0000261034 (ponatinib, Treatment of chronic myeloid leukaemia;Treatment of Philadelphia chromosome positive acute lymphoblastic leukaemia): PM: decision on the application for modification of an agreed PIP, 28 Apr 2025; EMEA-000727-PIP01-09-M07 (Bosutinib, Treatment of chronic myeloid leukaemia (CML)): PM: decision on the application for modification of an agreed PIP, 7 Aug 2023; compliance positive 15 Dec 2023; EMEA-002643-PIP01-19-M01 (imatinib, Treatment of acute lymphoblastic leukaemia;Treatment of chronic myeloid leukaemia): PM: decision on the application for modification of an agreed PIP, 29 Oct 2021; EMEA-002347-PIP01-18 (asciminib, Treatment of chronic myeloid leukaemia): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 29 Jan 2020; +4 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/3/26/3246 positive 22 Jun 2026: Treatment of Diamond-Blackfan anaemia; EU/3/21/2449 positive 21 Jun 2021: Treatment of pulmonary arterial hypertension; EU/3/09/715 expired 2 Feb 2010: Treatment of acute lymphoblastic leukaemia; EU/3/09/716 expired 2 Feb 2010: Treatment of chronic myeloid leukaemia; +16 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 · Glivec: authorised since 7 Nov 2001; Sprycel: authorised since 20 Nov 2006; Scemblix: authorised since 25 Aug 2022, orphan medicine; Iclusig: authorised since 1 Jul 2013; +13 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: yes · Bosutinib [Bosulif], 26 Sept 2023: Treatment of adult and pediatric patients 1 year of age and older with chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML), newly-diagnosed or resistant or intolerant to prior therapy; Imatinib Mesylate [Gleevec] &, 25 Jan 2013: Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy; Imatinib Mesylate [Gleevec] &, 27 Sept 2006: Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase; +4 moreRule: 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 · 198 interventional studies of bosutinib, ponatinib, nilotinib hydrochloride monohydrate, bosutinib monohydrate, asciminib, imatinib, dasatinib, nilotinib, olverembatinib, radotinib, vodobatinib include patients under 18; 39 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 15 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.