ERBB3 erb-b2 receptor tyrosine kinase 3
ENSG00000065361 · protein coding · Open Targets profile
Tyrosine kinase receptor that, despite substitutions of key catalytic residues in the kinase domain, retains residual catalytic activity enabling autophosphorylation (PubMed:9148746, PubMed:20351256). Functions primarily as a heterodimer, preferentially partnering with ERBB2/HER2, which phosphorylates ERBB3 on specific tyrosine residues and provides the kinase activity required for downstream signaling (PubMed:22983903). Binds neuregulins NRG1 and NRG2 through its extracellular domain, which induces conformational change from a tethered autoinhibited state to an extended conformation competent for dimerization (PubMed:20682778). Upon heterodimerization and trans-phosphorylation, acts as the most efficient activator of the PI3K/AKT pathway within the ErbB family (PubMed:22983903). Also activates the RAS/MAPK/ERK cascade to promote cell proliferation (PubMed:22983903). Plays an essential role in cardiac development; required for normal formation of the endocardial cushion and ventricular trabeculation during embryogenesis (Potential). Critical for peripheral nervous system development, where neuregulin-1/ERBB3 signaling drives Schwann cell survival, proliferation, and differentiation, and is required for axonal myelination (By similarity). Involved in epithelial morphogenesis and mammary gland development (By similarity). Also involved in the regulation of myeloid cell differentiation (PubMed:27416908). Participates in a regulatory feedback loop whereby pathway activation induces transcriptional up- regulation of ERBB3 expression (PubMed:21368164). Participates in vesicular sorting by stabilizing the ARF6-GGA3-RABEP1 endosomal sorting complex, to promote early recycling of TFRC and ITGB1 (PubMed:41348103). May also be activated by additional ligands including CSPG5 and EGFL6; the latter triggers assembly of an ERBB2/ERBB3/ITGB3 signaling complex leading to ERK phosphorylation and cell proliferation (PubMed:15358134, PubMed:41151154). {ECO:0000250|UniProtKB:Q61526, ECO:0000269|PubMed:15358134, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:21368164, ECO:0000269|PubMed:22983903, ECO:0000269|PubMed:27416908, ECO:0000269|PubMed:41151154, ECO:0000269|PubMed:41348103, ECO:0000269|PubMed:9148746}.
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
- Advanced Clinical, UniProt loc high conf, GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM, Human Protein Atlas loc
- PROTAC
- Half-life Data, Small Molecule Binder
- Other modalities
- Advanced Clinical
gnomAD loss of function constraint: o/e 0.6125199794769287 (upper bound 0.7257599830627441). 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 50 registry trials, updated in the last three years, of the most advanced drugs against ERBB3 (patritumab deruxtecan, zenocutuzumab, vandetanib, poziotinib, patritumab, duligotuzumab, seribantumab, MM-111, CDX-3379, istiratumab, sapitinib, tarloxotinib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Alison SchramMemorial Sloan Kettering Medical Center · 1 of 1 trials Phase 2+
- Barbara PISTILLIGustave Roussy, Cancer Campus, Grand Paris · 1 of 1 trials Phase 2+
- Erika HamiltonSCRI Development Innovations, LLC · 1 of 1 trials Phase 2+
- Ernesto WassermanMerus B.V. · 1 of 1 trials Phase 2+
- Fabrice ANDREGustave Roussy, Villejuif · 1 of 1 trials Phase 2+
- Fabrice BARLESICHU Hopital Nord Marseille · 1 of 1 trials Phase 2+
- Gary MiddletonRoyal Surrey County Hospital NHS Foundation Trust · 1 of 1 trials Phase 2+
- Jaba KokhreidzeSpectrum Pharmaceuticals, Inc · 1 of 1 trials Phase 2+
- Joop de LangenAntoni van Leeuwenhoek · 1 of 1 trials Phase 2+
- Laura EssermanUniversity of California, San Francisco · 1 of 1 trials Phase 2+
- Matthias PreusserMedical Oncologist. Head of Clinical Division of Oncology, Medical University of Vienna · 1 of 1 trials Phase 2+
- Physician ScientistDaiichi Sankyo · 1 of 1 trials Phase 2+
- Rupert BartschConsultant Hematology and Medical Oncology, Medical University of Vienna · 1 of 1 trials Phase 2+
- Se-Hoon LeeSamsung Medical Center · 1 of 1 trials Phase 2+
- Yasir Y ElaminM.D. Anderson Cancer Center · 1 of 1 trials Phase 2+
Registry trials of patritumab deruxtecan, zenocutuzumab, vandetanib, poziotinib, patritumab, duligotuzumab, seribantumab, MM-111, CDX-3379, istiratumab, sapitinib, tarloxotinib 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; 20 of 50 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. Source: ClinicalTrials.gov, fetched live.
57 trials of drugs against ERBB3 were stopped early; 2 give no reason
Terminated, withdrawn and suspended interventional trials of patritumab deruxtecan, zenocutuzumab, vandetanib, poziotinib, patritumab, duligotuzumab, seribantumab, MM-111, CDX-3379, istiratumab, sapitinib, tarloxotinib, 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 57.
- suspended · 2026-10-28 · Spectrum Pharmaceuticals, Inc · Poziotinib“The study has not enrolled any patients. The study design is under discussion and will likely be redesigned in consultation with the FDA.”
- terminated · 2026-07-28 · Spectrum Pharmaceuticals, Inc · Poziotinib“Business reasons, not related to safety.”
- terminated · 2026-06-12 · Spectrum Pharmaceuticals, Inc · Poziotinib“Strategic business decision (unrelated to safety)”
- terminated · 2026-04-27 · Partner Therapeutics, Inc. · matched by the registry's drug synonyms“Merus terminated the study early due to changes in organizational priorities.”
- terminated · 2026-02-20 · M.D. Anderson Cancer Center · Poziotinib“<75% participation”
- terminated · 2025-12-16 · Medical University of South Carolina · Sotorasib and Tarloxotinib“Study drug was discontinued by manufacturer for business reasons.”
- withdrawn · 2025-06-15 · Mustafa Khasraw, MBChB, MD, FRCP, FRACP · Patritumab deruxtecan“Study sponsor, Daiichi, decided to close for mult reasons, including drug near expiration, lack of enrollment, and their priority changes.”
- terminated · 2025-05-18 · Daiichi Sankyo · Patritumab Deruxtecan“Study was terminated early given the Interim Analysis for Part 1 (signal finding) did not meet pre-specified criteria and will not proceed to Part 2. Sponsor will proceed closing the study.”
- terminated · 2025-04-03 · Elevation Oncology · Seribantumab“Business decision”
- terminated · 2024-06-25 · Spectrum Pharmaceuticals, Inc · Poziotinib Once Daily Dosing, Poziotinib Twice Daily Dosing, Poziotinib Once Daily Dosing or Twice Daily Dosing as determined in Phase 1“Business decision, not related to safety.”
- terminated · 2024-03-13 · Spectrum Pharmaceuticals, Inc · Poziotinib Hydrochloride“Strategic business decision (unrelated to safety)”
- withdrawn · 2024-01-05 · Hoffmann-La Roche · Vandetanib“Due to several logistical challenges during start-up which could not be overcome study was withdrawn.”
- withdrawn · 2023-09-13 · M.D. Anderson Cancer Center · Poziotinib Hydrochloride, 1429757-68-5, HM781-36B, NOV-1201 Hydrochloride, NOV120101 Hydrochloride, Poziotinib HCl, POZIOTINIB HYDROCHLORIDE“Study closed due to funding, 0 patient accrual.”
- terminated · 2023-06-28 · Rain Oncology Inc · tarloxotinib bromide“enrollment pause”
- terminated · 2023-04-03 · Celldex Therapeutics · CDX-3379 and cetuximab“Sponsor decision based on emerging risk-benefit profile”
- terminated · 2023-01-12 · Rain Oncology Inc · TH-4000 (Tarloxotinib)“Lack of efficacy”
- terminated · 2023-01-12 · Rain Oncology Inc · TH-4000 (Tarloxotinib)“Lack of efficacy”
- terminated · 2021-11-01 · Ronald Weigel · Vandetanib“Drugs unavailable”
- terminated · 2021-10-12 · Elevation Oncology · matched by the registry's drug synonyms“Based on the preliminary results seen during interim analysis, which were confirmed in the final analysis, the Sponsor terminated the study”
- terminated · 2021-07-14 · H. Lee Moffitt Cancer Center and Research Institute · Vandetanib“Lack of efficacy”
- terminated · 2021-06-15 · Spectrum Pharmaceuticals, Inc · 14C-labeled poziotinib“COVID”
- terminated · 2021-01-26 · National Cancer Institute (NCI) · Vandetanib, Vandetanib/Metformin“Vandetanib is no longer available as Sanofi has decided not to provide additional drug. All subjects are off-study.”
- terminated · 2021-01-15 · Spectrum Pharmaceuticals, Inc · Poziotinib“Dose limiting toxicity”
- terminated · 2020-11-17 · Hanmi Pharmaceutical Company Limited · Poziotinib“Study termination by the Sponsor”
- terminated · 2020-09-02 · Elevation Oncology · Seribantumab“Merrimack Inc. terminated the trial early due to business decision”
Paediatric incentives and obligations for ERBB3's drugs
For patritumab deruxtecan, zenocutuzumab, vandetanib, poziotinib, patritumab, duligotuzumab, seribantumab, MM-111, CDX-3379, istiratumab, sapitinib, tarloxotinib: 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 · ERBB3 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-003519-PIP01-23 (zenocutuzumab, Treatment of lung cancer;Treatment of pancreatic cancer): W: decision granting a waiver in all age groups for all conditions or indications, 7 Mar 2024; EMEA-002977-PIP01-21 (patritumab deruxtecan, Treatment of lung cancer): W: decision granting a waiver in all age groups for all conditions or indications, 8 Jul 2021; EMEA-000052-PIP01-07-M03 (vandetanib, Treatment of medullary thyroid carcinoma): PM: decision on the application for modification of an agreed PIP, 30 Nov 2013; compliance positive 20 Jun 2014Rule: 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/3/05/344 withdrawn 24 Jan 2006: Treatment of medullary thyroid carcinomaRule: 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/3/05/344, 2026-11-11
- Authorised in the EU: yes · Caprelsa: authorised since 16 Feb 2012; Zactima: application withdrawnRule: 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 patritumab deruxtecan, zenocutuzumab, vandetanib, poziotinib, patritumab, duligotuzumab, seribantumab, mm-111, cdx-3379, istiratumab, sapitinib, tarloxotinibRule: 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 · 14 interventional studies of patritumab deruxtecan, zenocutuzumab, vandetanib, poziotinib, patritumab, duligotuzumab, seribantumab, mm-111, cdx-3379, istiratumab, sapitinib, tarloxotinib include patients under 18; 2 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 17 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.