ABL1 ABL proto-oncogene 1, non-receptor tyrosine kinase
ENSG00000097007 · protein coding · Open Targets profile
Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9 (PubMed:22810897). Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage- induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 also acts as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner (By similarity). Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity). {ECO:0000250|UniProtKB:P00520, ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:12531427, ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:16943190, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:17623672, ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:18945674, ECO:0000269|PubMed:19891780, ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:20417104, ECO:0000269|PubMed:22810897, ECO:0000269|PubMed:28428613, ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}.
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
- GO CC med conf
- PROTAC
- Literature, UniProt Ubiquitination, Database Ubiquitination, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.11618000268936157 (upper bound 0.1923000067472458). 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 ABL1 (ponatinib, asciminib, umbralisib, bosutinib monohydrate, nilotinib hydrochloride monohydrate, bosutinib, nilotinib, dasatinib, regorafenib, imatinib, ruserontinib, radotinib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Elias JabbourM.D. Anderson Cancer Center · 8 of 8 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+
- Jean-Yves BLAYCentre Leon Berard · 2 of 3 trials Phase 2+Ph2NCT02029001 · Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatmentbrief
- Marwan G FakihCity of Hope Medical Center · 2 of 3 trials Phase 2+Ph1/Ph2NCT05672316 · Botensilimab, Balstilimab and Regorafenib for the Treatment of Patients With Microsatellite Stable Metastatic Colorectal Cancer Who Have Progressed on Prior Chemotherapybrief
- 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+
- Kanwal RaghavM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
- Lin ShenPeking University Cancer Hospital & Institute · 2 of 2 trials Phase 2+
- Mehdi BRAHMICentre Leon Berard · 2 of 2 trials Phase 2+
- Nicholas ShortM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
Registry trials of ponatinib, asciminib, umbralisib, bosutinib monohydrate, nilotinib hydrochloride monohydrate, bosutinib, nilotinib, dasatinib, regorafenib, imatinib, ruserontinib, radotinib 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; 308 of 385 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. 15 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
300 trials of drugs against ABL1 were stopped early; 16 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of ponatinib, asciminib, umbralisib, bosutinib monohydrate, nilotinib hydrochloride monohydrate, bosutinib, nilotinib, dasatinib, regorafenib, imatinib, ruserontinib, radotinib, 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 300.
- terminated · 2026-11-04 · City of Hope Medical Center · dasatinib“Terminated early due a shift in resources after lackluster performance of the drug.”
- terminated · 2026-11-03 · Peking University Cancer Hospital & Institute · regorafenib“The study was stopped early due to lack of efficacy.”
- suspended · 2026-10-20 · City of Hope Medical Center · Regorafenib“resources”
- terminated · 2026-10-05 · Children's Oncology Group · Regorafenib“Drug supply issues”
- suspended · 2026-10-01 · Institut Paoli-Calmettes · Dasatinib“Planned interim analyse”
- terminated · 2026-08-26 · Bristol-Myers Squibb · RegorafenibNo reason given
- 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 · 2026-07-06 · Syndax Pharmaceuticals · matched by the registry's drug synonyms“Study was terminated by sponsor after Phase 1b as pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort.”
- withdrawn · 2026-06-15 · University of Miami · Regorafenib“Investigator decision”
- terminated · 2026-05-29 · Sarit Assouline · Asciminib, Imatinib“Insufficient patient accrual”
- terminated · 2026-05-13 · Sun Pharma Advanced Research Company Limited · matched by the registry's drug synonyms“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”
- withdrawn · 2026-03-11 · M.D. Anderson Cancer Center · Regorafenib“0 participants enrolled”
- terminated · 2026-03-09 · Translational Research in Oncology · Regorafenib in combination with pembrolizumab“The trial ended earlier than planned due to slow enrolment, which has made it unfeasible to achieve the target sample size within a reasonable timeframe. Consequently, a business decision has been made to discontinue funding for the trial.”
- terminated · 2026-03-05 · Wake Forest University Health Sciences · Regorafenib“Slow accruals”
- terminated · 2026-03-02 · M.D. Anderson Cancer Center · Asciminib“75% < Participants, Administrativley Complete”
- terminated · 2026-02-27 · Massachusetts General Hospital · Umbralisib“Umbralisib development terminated; closed to accrual 8/29/2022”
- withdrawn · 2026-02-25 · M.D. Anderson Cancer Center · Regorafenib“0 participants enrolled”
- terminated · 2026-01-29 · Indiana University · Imatinib Mesylate“low accrual”
- terminated · 2026-01-20 · Anwaar Saeed · Regorafenib“Terminated per directive from Bayer due to funding.”
- terminated · 2026-01-06 · H. Lee Moffitt Cancer Center and Research Institute · Umbralisib“Drug no longer available”
- 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”
Paediatric incentives and obligations for ABL1's drugs
For ponatinib, asciminib, umbralisib, bosutinib monohydrate, nilotinib hydrochloride monohydrate, bosutinib, nilotinib, dasatinib, regorafenib, imatinib, ruserontinib, radotinib: 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: yes · ABL1 is on the list. Membership alone neither requires nor waives a pediatric study.Rule: 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; EMA/PE/0000182170 (regorafenib, Treatment of all conditions contained in the category of malignant neoplasms (except haematopoietic and lymphoid tissue)): PM: decision on the application for modification of an agreed PIP, 5 Dec 2024; 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; +6 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; +14 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; Nilotinib [Tasigna], 22 Mar 2018: Treatment of adult and pediatric patients greater than or equal to 1 year of age with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase; Nilotinib [Tasigna], 22 Mar 2018: Treatment of pediatric patients greater than or equal to 1 year of age with chronic phase and accelerated phase Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) with resistance or intolerance to prior tyrosine-kinase inhibitor (TKI) therapy; +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 · 202 interventional studies of ponatinib, asciminib, umbralisib, bosutinib monohydrate, nilotinib hydrochloride monohydrate, bosutinib, nilotinib, dasatinib, regorafenib, imatinib, ruserontinib, radotinib include patients under 18; 38 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 27 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.