TEK TEK receptor tyrosine kinase
ENSG00000120156 · protein coding · Open Targets profile
Tyrosine-protein kinase that acts as a cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of pro-inflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1 and TIE1. {ECO:0000269|PubMed:12816861, ECO:0000269|PubMed:14665640, ECO:0000269|PubMed:15284220, ECO:0000269|PubMed:15851516, ECO:0000269|PubMed:18366015, ECO:0000269|PubMed:18425119, ECO:0000269|PubMed:18425120, ECO:0000269|PubMed:19223473, ECO:0000269|PubMed:20651738, ECO:0000269|PubMed:9204896}.
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
- UniProt Ubiquitination, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.326339989900589 (upper bound 0.4208199977874756). 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 195 registry trials, updated in the last three years, of the most advanced drugs against TEK (regorafenib, vandetanib, foretinib, CEP-11981, glesatinib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Kanwal RaghavM.D. Anderson Cancer Center · 3 of 3 trials Phase 2+Ph2NCT07071961 · Regorafenib (Reg) and Lorigerlimab (Lor), RELO Regimen, in Treatment of High-risk Patients With Colorectal Cancer With Radiographic Occult Molecular Residual Disease After End of Established Definitive Therapy [ReLOAD Trial]brief
- 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
- Lin ShenPeking University Cancer Hospital & Institute · 2 of 2 trials Phase 2+
- Nicolas PENELCentre Oscar Lambret · 2 of 2 trials Phase 2+
- Ying YuanSecond Affiliated Hospital, Zhejiang University, School of Medicine · 2 of 2 trials Phase 2+
- Florence DUFFAUDLa Timone University Hospital · 1 of 2 trials Phase 2+
- Jean-Yves BLAYCentre Leon Berard · 1 of 2 trials Phase 2+
- Abdullah EsmailHouston Methodist Neal Cancer Center · 1 of 1 trials Phase 2+
- Aiping ZhouCancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College · 1 of 1 trials Phase 2+
- Alan HoMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
- Alisha H BentM.D. Anderson Cancer Center · 1 of 1 trials Phase 2+
- Andrea CercekMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
- Andrew KennedySCRI Development Innovations, LLC · 1 of 1 trials Phase 2+
- Anna Raciborskathe Institue of Mother and Child · 1 of 1 trials Phase 2+
- Antoine AdenisInstitut régional du cancer de Montpellier · 1 of 1 trials Phase 2+
Registry trials of regorafenib, vandetanib, foretinib, CEP-11981, glesatinib 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; 146 of 179 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. 16 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
76 trials of drugs against TEK were stopped early; 12 give no reason
Terminated, withdrawn and suspended interventional trials of regorafenib, vandetanib, foretinib, CEP-11981, glesatinib, pexmetinib, altiratinib, 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 76.
- 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”
- terminated · 2026-08-26 · Bristol-Myers Squibb · RegorafenibNo reason given
- 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”
- 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”
- withdrawn · 2026-02-25 · M.D. Anderson Cancer Center · Regorafenib“0 participants enrolled”
- terminated · 2026-01-20 · Anwaar Saeed · Regorafenib“Terminated per directive from Bayer due to funding.”
- terminated · 2025-03-30 · UNICANCER · Regorafenib then Trifluridine/Tipiracil, Trifluridine/Tipiracil then Regorafenib“Following the presentation of the SUNLIGHT study results at ASCO GI and the rapid change in patient management in the majority of centers, the IDMC experts recommended halting inclusion in the SOREGATT study with immediate effect.”
- terminated · 2025-03-11 · Great Novel Therapeutics Biotech & Medicals Corporation · Regorafenib“The overall profile does not support development for Hepatocellular Carcinoma”
- terminated · 2024-12-11 · ImmunityBio, Inc. · Regorafenib“low enrollment”
- withdrawn · 2024-11-21 · City of Hope Medical Center · Regorafenib“Abandoned 9/23/24”
- terminated · 2024-07-16 · Barbara Ann Karmanos Cancer Institute · Pan-VEGFR/TIE2 Tyrosine Kinase Inhibitor CEP-11981“The study was closed to accrual on 3/1/21 due to safety concerns since 2 patients experienced CVA events.”
- terminated · 2024-06-26 · Wake Forest University Health Sciences · Regorafenib“Funder terminated.”
- terminated · 2024-06-05 · Theseus Pharmaceuticals · matched by the registry's drug synonyms“The Sponsor terminated the study due to early dose-limiting toxicities.”
- withdrawn · 2024-04-29 · M.D. Anderson Cancer Center · Regorafenib“0 participant accrual”
- terminated · 2024-04-22 · Mirati Therapeutics Inc. · Glesatinib“This study was terminated as a result of Sponsor portfolio reprioritization.”
- terminated · 2024-03-04 · OHSU Knight Cancer Institute · Regorafenib“Low accrual”
- terminated · 2024-02-07 · Dana-Farber Cancer Institute · matched by the registry's drug synonyms“Difficulty with patient recruitment”
- withdrawn · 2024-01-05 · Hoffmann-La Roche · Vandetanib“Due to several logistical challenges during start-up which could not be overcome study was withdrawn.”
- terminated · 2023-11-07 · Hoffmann-La Roche · Regorafenib“The Sponsor made the decision to terminate the study due to start up and recruitment issues caused by limited resource availability at the treating centers.”
- terminated · 2023-10-23 · Case Comprehensive Cancer Center · Regorafenib“PI discretion based on low accrual”
Paediatric incentives and obligations for TEK's drugs
For regorafenib, vandetanib, foretinib, CEP-11981, glesatinib, pexmetinib, altiratinib: 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 · TEK 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/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-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/3/19/2177 withdrawn 28 Jun 2019: Treatment of glioma; 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 data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Caprelsa: authorised since 16 Feb 2012; Stivarga: authorised since 26 Aug 2013; 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 regorafenib, vandetanib, foretinib, cep-11981, glesatinib, pexmetinib, altiratinibRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 24 interventional studies of regorafenib, vandetanib, foretinib, cep-11981, glesatinib, pexmetinib, altiratinib include patients under 18; 7 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, 2026-11-12
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 7 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.