ALK ALK receptor tyrosine kinase
ENSG00000171094 · protein coding · Open Targets profile
Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system (PubMed:11121404, PubMed:11387242, PubMed:16317043, PubMed:17274988, PubMed:30061385, PubMed:34646012, PubMed:34819673). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:30061385, PubMed:33411331, PubMed:34646012, PubMed:34819673). In contrast, ALKAL1 is not a potent physiological ligand for ALK (PubMed:34646012). Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (PubMed:34819673). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (PubMed:15226403, PubMed:16878150). Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 (PubMed:15226403, PubMed:16878150). ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK) (PubMed:11278720, PubMed:11809760, PubMed:12107166, PubMed:12122009). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720, PubMed:11809760, PubMed:12107166). MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction (PubMed:12122009). Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase (PubMed:15226403, PubMed:16878150). Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK (PubMed:15226403, PubMed:16878150). May function as regulator of gastric epithelial differentiation (By similarity). {ECO:0000250|UniProtKB:P97793, ECO:0000269|PubMed:11121404, ECO:0000269|PubMed:11278720, ECO:0000269|PubMed:11387242, ECO:0000269|PubMed:11809760, ECO:0000269|PubMed:12107166, ECO:0000269|PubMed:12122009, ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:16317043, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:30061385, ECO:0000269|PubMed:33411331, ECO:0000269|PubMed:34646012, ECO:0000269|PubMed:34819673}.
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, UniProt SigP or TMHMM, Human Protein Atlas loc
- PROTAC
- Literature, Database Ubiquitination, Small Molecule Binder
- Other modalities
- Phase 1 Clinical
gnomAD loss of function constraint: o/e 0.4535999894142151 (upper bound 0.5504000186920166). 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 200 registry trials, updated in the last three years, of the most advanced drugs against ALK (alectinib, brigatinib, entrectinib, lorlatinib, crizotinib, ceritinib, ensartinib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Yongchang ZhangHunan Cancer Hospital · 4 of 4 trials Phase 2+
- Matthew KrebsThe Christie Hospital · 3 of 3 trials Phase 2+Ph2/Ph3NCT05722886 · DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial) - Master Screening Protocolbrief
- Michael DURUISSEAUXHospices Civils de Lyon - Hôpital Louis Pradel · 3 of 3 trials Phase 2+
- Yasir Y ElaminM.D. Anderson Cancer Center · 2 of 4 trials Phase 2+
- Caicun ZhouShanghai East Hospital · 2 of 2 trials Phase 2+
- David S HongECOG-ACRIN Cancer Research Group · 2 of 2 trials Phase 2+
- Denis Moro-SibilotGrenoble - CHU · 2 of 2 trials Phase 2+
- Giovanni SelvaggiCEO · 1 of 2 trials Phase 2+
- Yi-Long WuGuangdong Provincial People's Hospital · 1 of 2 trials Phase 2+
- A.J. van der WekkenUniversity Medical Center Groningen · 1 of 1 trials Phase 2+
- Aaron S MansfieldECOG-ACRIN Cancer Research Group · 1 of 1 trials Phase 2+
- Aditi BagchiSt. Jude Children's Research Hospital · 1 of 1 trials Phase 2+
- Alex MenziesMelanoma Institute Australia · 1 of 1 trials Phase 2+
- Alexander ShoushtariMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
- Alice T ShawECOG-ACRIN Cancer Research Group · 1 of 1 trials Phase 2+
Registry trials of alectinib, brigatinib, entrectinib, lorlatinib, crizotinib, ceritinib, ensartinib 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; 124 of 183 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. 17 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
48 trials of drugs against ALK were stopped early; 6 give no reason
Terminated, withdrawn and suspended interventional trials of alectinib, brigatinib, entrectinib, lorlatinib, crizotinib, ceritinib, ensartinib, conteltinib, PLB1003, ASP-3026, CEP-37440, 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 48.
- terminated · 2026-07-21 · ETOP IBCSG Partners Foundation · Alectinib“Low recruitment rate”
- suspended · 2026-06-05 · Megan Kruse, MD · matched by the registry's drug synonyms“Anheart acquired by Nuvation Bio; leadership not moving forward”
- terminated · 2026-06-04 · Pfizer · lorlatinib“The study was prematurely discontinued due to strategic reasons. The PF-07284892 program will continue”
- terminated · 2026-04-23 · National Cancer Institute (NCI) · Alectinib, Brigatinib, Ceritinib, Crizotinib, Ensartinib, Lorlatinib“Inadequate accrual rate”
- terminated · 2026-03-10 · Yael P Mosse · Ceritinib“The goals of Part 1 (molecular screening) were met, but lack of therapies to match molecular aberrations made Part 2 (treatment) no longer feasible.”
- terminated · 2025-07-16 · National Cheng-Kung University Hospital · Crizotinib 250 MG“Patients were recruited during screen phase but fewer patients met criteria.”
- terminated · 2025-05-13 · Massachusetts General Hospital · Alectinib“slow accrual”
- withdrawn · 2025-04-24 · M.D. Anderson Cancer Center · Brigatinib“0 participants enrolled”
- terminated · 2025-01-23 · Pfizer · Crizotinib“Termination of further treatment on the study due to the availability of commercial supply or a rollover study (NCT05160922) that will allow active subjects to continue receiving treatment.”
- terminated · 2025-01-08 · Strata Oncology · lorlatinib“Business decision and enrollment difficulties”
- terminated · 2024-11-08 · Pfizer · Crizotinib“The trial is terminated based on business decision, not due to safety concerns or regulatory requirements.”
- withdrawn · 2024-10-08 · ETOP IBCSG Partners Foundation · Brigatinib“Despite our efforts, the trial faced challenges like a longer activation period and slower accrual. We proposed a redesign, but TAKEDA withdrew. As a non-profit organisation, we can't continue without TAKEDA's support and must discontinue the trial.”
- terminated · 2024-06-21 · Pfizer · lorlatinib“The study stopped due to lack of enrollment”
- terminated · 2024-04-26 · Suzhou Zelgen Biopharmaceuticals Co.,Ltd · matched by the registry's drug synonyms“Sponsor R\&D Strategy Adjustment”
- terminated · 2024-03-04 · OHSU Knight Cancer Institute · Entrectinib, Lorlatinib“Low accrual”
- withdrawn · 2024-01-23 · OHSU Knight Cancer Institute · Alectinib, Entrectinib“Withdrawn due to a change in therapeutic interventions.”
- withdrawn · 2023-12-13 · SCRI Development Innovations, LLC · Lorlatinib“Study withdrawn by pharmaceutical funding partner”
- terminated · 2023-11-22 · Arkadiusz Z. Dudek, MD · Entrectinib“This study required dose reductions to the lower dose level (Dose level -1). But this dose level (Dose level -1) was not further explored because of lack of funding.”
- terminated · 2023-08-07 · Hoffmann-La Roche · Alectinib“The data from this study is no longer needed.”
- terminated · 2023-07-07 · Pfizer · Crizotinib“The study was terminated since there was no need for further safety or efficacy data to be collected. The participants having benefit from the Investigational treatments have been moved to a continuation study (NCT05059522)”
- terminated · 2023-02-03 · University of Texas Southwestern Medical Center · Ceritinib“The study was terminated after UTSW was informed by Novartis that further support for the study would not be provided”
- terminated · 2023-01-26 · Criterium, Inc. · brigatinib“Did not meet enrollment objectives.”
- terminated · 2022-12-27 · University of California, San Francisco · Ceritinib“Low Accrual”
- terminated · 2022-11-03 · Wake Forest University Health Sciences · Crizotinib“Study closed to accrual due to low accrual numbers.”
- terminated · 2022-10-24 · University of Colorado, Denver · Brigatinib“Low accrual”
Paediatric incentives and obligations for ALK's drugs
For alectinib, brigatinib, entrectinib, lorlatinib, crizotinib, ceritinib, ensartinib, conteltinib, PLB1003, ASP-3026, CEP-37440: 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 · ALK 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/0000236723 (brigatinib, Treatment of anaplastic large cell lymphoma): PM: decision on the application for modification of an agreed PIP, 15 Apr 2025; EMEA-002096-PIP01-16-M03 (Entrectinib, Treatment of all conditions included in the category of malignant neoplasms (except haematopoietic and lymphoid tissue neoplasms)): PM: decision on the application for modification of an agreed PIP, 8 Sept 2021; compliance positive 24 Feb 2023; EMEA-001493-PIP03-18-M01 (crizotinib, Treatment of anaplastic large cell lymphoma;Treatment of inflammatory myofibroblastic tumours): PM: decision on the application for modification of an agreed PIP, 27 Jan 2021; compliance positive 31 Mar 2023; EMEA-002431-PIP02-21 (alectinib, Treatment of all conditions included in the category of malignant neoplasms (except haematopoietic and lymphoid tissue neoplasms)): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 31 Jan 2022; +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/3/15/1580 withdrawn 11 Nov 2015: Treatment of neuroblastomaRule: 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 EU/3/15/1580, 2026-11-11
- Authorised in the EU: yes · Rozlytrek: authorised since 31 Jul 2020, conditional; Xalkori: authorised since 23 Oct 2012; Gevalka: opinion; Lorviqua: authorised since 6 May 2019; +3 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 · Entrectinib [Rozlytrek], 20 Oct 2023: Treatment of adult and pediatric patients older than 1 month with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory standard therapy; Crizotinib [Xalkori], 14 Jul 2022: Treatment of adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive; Crizotinib [Xalkori], 14 Jan 2021: Treatment of pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positiveRule: 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 alectinib, brigatinib, entrectinib, lorlatinib, crizotinib, ceritinib, ensartinib, conteltinib, plb1003, asp-3026, cep-37440 include patients under 18; 22 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 12 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.