FLT4 fms related receptor tyrosine kinase 4
ENSG00000037280 · protein coding · Open Targets profile
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'. {ECO:0000269|PubMed:11532940, ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:15474514, ECO:0000269|PubMed:16076871, ECO:0000269|PubMed:16452200, ECO:0000269|PubMed:17210781, ECO:0000269|PubMed:19610651, ECO:0000269|PubMed:19779139, ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20431062, ECO:0000269|PubMed:20445537, ECO:0000269|PubMed:21273538, ECO:0000269|PubMed:7675451, ECO:0000269|PubMed:8700872, ECO:0000269|PubMed:9435229}.
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 Withdrawn means the drug was pulled from the market or from development.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, High-Quality Ligand, Druggable Family
- Antibody
- Phase 1 Clinical, UniProt loc high conf, GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM
- PROTAC
- Database Ubiquitination, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.18378999829292297 (upper bound 0.24929000437259674). 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 FLT4 (tivozanib, lenvatinib, nintedanib esylate, sorafenib, surufatinib, axitinib, cediranib, pazopanib, sunitinib, fruquintinib, vandetanib, regorafenib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Jihui HaoTianjin Medical University Cancer Institute and Hospital · 3 of 3 trials Phase 2+Ph2NCT05908747 · Efficacy and Safety of Surufatinib Combined With Gemcitabine and Albumin-bound Paclitaxel in the Peri-operative Treatment of Pancreatic Cancerbrief
- Joyce F LiuNRG Oncology · 3 of 3 trials Phase 2+Ph3NCT02446600 · Testing the Use of A Single Drug (Olaparib) or the Combination of Two Drugs (Cediranib and Olaparib) Compared to the Usual Chemotherapy for Women With Platinum Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancerbrief
- Lin ShenPeking University Cancer Hospital & Institute · 3 of 3 trials Phase 2+
- Alan HoMemorial Sloan Kettering Cancer Center · 2 of 2 trials Phase 2+
- Amado ZuritaM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
- Dingwei YeFudan University · 2 of 2 trials Phase 2+
- Eric JonaschM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
- Jean-Yves BLAYCentre Leon Berard · 2 of 2 trials Phase 2+
- Jessica GartrellSt. Jude Children's Research Hospital · 2 of 2 trials Phase 2+
- Joseph W KimYale University Cancer Center LAO · 2 of 2 trials Phase 2+
- Jung-min LeeNRG Oncology · 2 of 2 trials Phase 2+
- Kanwal RaghavM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
- Maen AbdelrahimThe Methodist Hospital Research Institute · 2 of 2 trials Phase 2+
- Song GaoTianjin Medical University Cancer Institute and Hospital · 2 of 2 trials Phase 2+
- Vincent ChungCity of Hope Medical Center · 2 of 2 trials Phase 2+
Registry trials of tivozanib, lenvatinib, nintedanib esylate, sorafenib, surufatinib, axitinib, cediranib, pazopanib, sunitinib, fruquintinib, vandetanib, regorafenib 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; 273 of 370 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. 30 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
493 trials of drugs against FLT4 were stopped early; 12 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of tivozanib, lenvatinib, nintedanib esylate, sorafenib, surufatinib, axitinib, cediranib, pazopanib, sunitinib, fruquintinib, vandetanib, regorafenib, 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 493.
- 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”
- withdrawn · 2026-10-01 · City of Hope Medical Center · Tivozanib“Study Abandoned withdrawn”
- terminated · 2026-09-03 · Merck Sharp & Dohme LLC · Lenvatinib“Business Reasons”
- terminated · 2026-08-26 · Bristol-Myers Squibb · RegorafenibNo reason given
- terminated · 2026-08-25 · Association of Urologic Oncology (AUO) · SunitinibNo reason given
- terminated · 2026-08-21 · Merck Sharp & Dohme LLC · Lenvatinib“Trial was rendered as cancelled work ongoing in the book of business.”
- terminated · 2026-08-12 · Providence Health & Services · Lenvatinib“PI opted to close study due to poor accrual.”
- terminated · 2026-07-29 · EMD Serono Research & Development Institute, Inc. · Lenvatinib“The study was stopped due to a lack of clear evidence of anti-tumor activity with the combination treatment in the participants treated.”
- 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 · 2026-06-11 · Changhai Hospital · Surufatinib“This investigator-initiated study closed to recruitment early due to slower-than-anticipated patient accrual.”
- suspended · 2026-06-05 · Shanghai 6th People's Hospital · fruquintinib“Recruitment is temporarily suspended to allow for operational adjustments at the study sites. The trial will resume once all site readiness requirements are met”
- terminated · 2026-06-04 · Pfizer · Axitinib“Pfizer has made an internal business decision to not continue further development of PF-07265807. This decision was not due to major safety concerns or requests from any regulatory authorities.”
- terminated · 2026-06-04 · Incyte Corporation · axitinib“This was a strategic business decision. There were no safety concerns contributing to this decision.”
- terminated · 2026-06-04 · Yale University · Lenvatinib“Lack of activity in the drugs”
- terminated · 2026-05-20 · Massachusetts General Hospital · Tivozanib“Slow accrual”
- terminated · 2026-04-30 · RenJi Hospital · Lenvatinib Oral Product Plus VIC1911“The study was terminated because the originally planned VIC-1911 dose-escalation scheme (100 mg, 150 mg, 200 mg BID) was scientifically unjustified, lacking prior clinical safety data to support such starting doses when combined with lenvatinib in HC”
- terminated · 2026-04-24 · Emory University · Lenvatinib“Slow Accrual”
- terminated · 2026-04-14 · Institut Claudius Regaud · Pazopanib“Slow recruitment rate”
- 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.”
- suspended · 2026-03-06 · H. Lee Moffitt Cancer Center and Research Institute · Axitinib“Funding unavailable”
- terminated · 2026-03-05 · Wake Forest University Health Sciences · Regorafenib“Slow accruals”
Paediatric incentives and obligations for FLT4's drugs
For tivozanib, lenvatinib, nintedanib esylate, sorafenib, surufatinib, axitinib, cediranib, pazopanib, sunitinib, fruquintinib, vandetanib, regorafenib: 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 · FLT4 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-001119-PIP02-12-M08 (lenvatinib, Treatment of follicular thyroid cancer;Treatment of osteosarcoma;Treatment of papillary thyroid cancer): PM: decision on the application for modification of an agreed PIP, 10 Aug 2022; compliance positive 26 May 2023; EMEA-001119-PIP03-19-M03 (lenvatinib, Treatment of all conditions included in the category of malignant neoplasms except haematopoietic and lymphoid tissue neoplasms, papillary thyroid cancer, follicular thyroid cancer and osteosarcoma): PM: decision on the application for modification of an agreed PIP, 30 Dec 2022; compliance positive 13 Oct 2023; EMEA-002750-PIP01-19 (surufatinib, Treatment of all conditions included in the category of malignant neoplasms (except central nervous system tumours, haematopoietic and lymphoid tissue neoplasms);Treatment of malignant neoplasms of haematopoietic and lymphoid tissue): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 14 Apr 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/3/13/1200 expired 13 Nov 2013: Treatment of papillary thyroid cancer; EU/3/13/1199 expired 13 Nov 2013: Treatment of follicular thyroid cancer; EU/3/19/2177 withdrawn 28 Jun 2019: Treatment of glioma; - negative 23 Sept 2019: Treatment of hepatocellular carcinoma; +9 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 · Sunitinib Accord: authorised since 11 Feb 2021; Fruzaqla: authorised since 20 Jun 2024; Caprelsa: authorised since 16 Feb 2012; Sorafenib Accord: authorised since 9 Nov 2022; +12 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: no · FDA's table lists no pediatric approval of tivozanib, lenvatinib, nintedanib esylate, sorafenib, surufatinib, axitinib, cediranib, pazopanib, sunitinib, fruquintinib, vandetanib, regorafenibRule: 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 · 166 interventional studies of tivozanib, lenvatinib, nintedanib esylate, sorafenib, surufatinib, axitinib, cediranib, pazopanib, sunitinib, fruquintinib, vandetanib, regorafenib include patients under 18; 45 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 47 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.