NTRK2 neurotrophic receptor tyrosine kinase 2
ENSG00000148053 · protein coding · Open Targets profile
Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity (By similarity). Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2 (PubMed:15494731, PubMed:7574684). Upon ligand- binding, undergoes homodimerization, autophosphorylation and activation (PubMed:15494731). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia. {ECO:0000250|UniProtKB:P15209, ECO:0000269|PubMed:15494731, ECO:0000269|PubMed:7574684}.
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 Withdrawn means the drug was pulled from the market or from development.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
- UniProt loc high conf, GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM, Human Protein Atlas loc
- PROTAC
- Literature, UniProt Ubiquitination, Half-life Data, Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 0.1376200020313263 (upper bound 0.21881000697612762). 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 81 registry trials, updated in the last three years, of the most advanced drugs against NTRK2 (lestaurtinib, larotrectinib, entrectinib, repotrectinib, cenegermin, taletrectinib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Flavio MantelliDompé Farmaceutici S.p.A · 6 of 7 trials Phase 2+Ph2NCT06244316 · A Safety and Efficacy Study of 2 Dosing Regimens of Recombinant Human Nerve Growth Factor (rhNGF) Eye Drop Solution Compared With Vehicle in Patients With Dry Eye Disease.brief
- Bristol-Myers SquibbBristol-Myers Squibb · 3 of 4 trials Phase 2+
- David S HongECOG-ACRIN Cancer Research Group · 2 of 2 trials Phase 2+
- Matthew KrebsThe Christie Hospital · 2 of 2 trials Phase 2+
- Aditi BagchiSt. Jude Children's Research Hospital · 1 of 1 trials Phase 2+
- Arkadiusz DudekHealth Partners Institute · 1 of 1 trials Phase 2+
- Åslaug HellandOslo University Hospital · 1 of 1 trials Phase 2+
- Brad KligmanSightMD, New York, New York · 1 of 1 trials Phase 2+
- Caicun ZhouShanghai East Hospital · 1 of 1 trials Phase 2+
- Daniel MoreiraSt. Jude Children's Research Hospital · 1 of 1 trials Phase 2+
- David HongUT MD Anderson · 1 of 1 trials Phase 2+
- Donald W ParsonsChildren's Oncology Group · 1 of 1 trials Phase 2+
- Dongmei JiFudan University · 1 of 1 trials Phase 2+
- E.E. VoestThe Netherlands Cancer Institute · 1 of 1 trials Phase 2+
- Emily SlotkinMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
Registry trials of lestaurtinib, larotrectinib, entrectinib, repotrectinib, cenegermin, taletrectinib 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; 43 of 76 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. 5 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
15 trials of drugs against NTRK2 were stopped early; 1 give no reason
Terminated, withdrawn and suspended interventional trials of lestaurtinib, larotrectinib, entrectinib, repotrectinib, cenegermin, taletrectinib, CEP-2563, altiratinib, AZD-6918, PLX-7486, selitrectinib, AZD-7451, 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 15 most recent of 15.
- suspended · 2026-06-05 · Megan Kruse, MD · Taletrectinib“Anheart acquired by Nuvation Bio; leadership not moving forward”
- terminated · 2026-01-05 · M.D. Anderson Cancer Center · Repotrectinib“<75% Participation”
- withdrawn · 2025-04-01 · Turning Point Therapeutics, Inc. · matched by the registry's drug synonyms“Insufficient enrollment”
- withdrawn · 2024-12-02 · Dompé Farmaceutici S.p.A · matched by the registry's drug synonyms“The study was withdrawn prior to enrolling subjects due to realignment of strategic priorities.”
- terminated · 2024-04-02 · Turning Point Therapeutics, Inc. · matched by the registry's drug synonyms“Inability to achieve and optimize a dose that could provide a positive benefit risk profile”
- terminated · 2024-03-04 · OHSU Knight Cancer Institute · Entrectinib“Low accrual”
- withdrawn · 2024-01-23 · OHSU Knight Cancer Institute · Entrectinib“Withdrawn due to a change in therapeutic interventions.”
- 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.”
- withdrawn · 2023-09-26 · Turning Point Therapeutics, Inc. · repotrectinib (TPX-0005)“Insufficient enrollment”
- terminated · 2023-08-07 · Hoffmann-La Roche · matched by the registry's drug synonyms“The data from this study is no longer needed.”
- withdrawn · 2023-01-26 · Tufts Medical Center · Cenegermin-Bkbj“Funding of study was withdrawn”
- terminated · 2020-01-27 · University of California, San Francisco · Entrectinib“Funding”
- terminated · 2018-08-02 · Plexxikon · matched by the registry's drug synonyms“Discontinued”
- terminated · 2012-08-23 · Cephalon · matched by the registry's drug synonymsNo reason given
- terminated · 2010-12-10 · AstraZeneca · matched by the registry's drug synonyms“PK results demonstrate low and variable plasma concentrations so that achieving therapeutic concentrations is unlikely.”
Paediatric incentives and obligations for NTRK2's drugs
For lestaurtinib, larotrectinib, entrectinib, repotrectinib, cenegermin, taletrectinib, CEP-2563, altiratinib, AZD-6918, PLX-7486, selitrectinib, AZD-7451: 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 · NTRK2 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 · 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-001971-PIP02-16-M04 (Larotrectinib, Treatment of all conditions included in the category of malignant neoplasms (except central nervous system tumours, haematopoietic and lymphoid tissue neoplasms)): PM: decision on the application for modification of an agreed PIP, 3 Dec 2021; compliance positive 31 Mar 2023; EMEA-002635-PIP02-21-M02 (repotrectinib, Treatment of all conditions included in the category of malignant neoplasms (except haematopoietic neoplasms)): PM: decision on the application for modification of an agreed PIP, 9 Aug 2023; EMEA-001971-PIP03-18-M02 (Larotrectinib, Treatment of malignant neoplasms of the central nervous system): PM: decision on the application for modification of an agreed PIP, 11 Aug 2022; +1 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/3/18/1995 withdrawn 21 Mar 2018: Treatment of salivary gland cancer; EU/3/15/1606 withdrawn 11 Jan 2016: Treatment of soft tissue sarcoma; EU/3/18/2097 withdrawn 19 Nov 2018: Treatment of glioma; EU/3/18/2098 withdrawn 19 Nov 2018: Treatment of papillary thyroid cancer; +3 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 · Rozlytrek: authorised since 31 Jul 2020, conditional; Vitrakvi: authorised since 19 Sept 2019, conditional; Augtyro: authorised since 13 Jan 2025, conditional; Oxervate: authorised since 6 Jul 2017, orphan medicineRule: 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 · Larotrectinib [Vitrakvi], 26 Nov 2018: Treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine 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 no satisfactory alternative treatments or that have progressed following treatment; 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; Repotrectinib [Augtyro], 13 Jun 2024: Treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, are locally advanced or metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapyRule: 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 · 24 interventional studies of lestaurtinib, larotrectinib, entrectinib, repotrectinib, cenegermin, taletrectinib, cep-2563, altiratinib, azd-6918, plx-7486, selitrectinib, azd-7451 include patients under 18; 19 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 13 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.