KDR kinase insert domain receptor
ENSG00000128052 · protein coding · Open Targets profile
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC. {ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:10368301, ECO:0000269|PubMed:10600473, ECO:0000269|PubMed:11387210, ECO:0000269|PubMed:12649282, ECO:0000269|PubMed:1417831, ECO:0000269|PubMed:15026417, ECO:0000269|PubMed:15215251, ECO:0000269|PubMed:15962004, ECO:0000269|PubMed:16966330, ECO:0000269|PubMed:17303569, ECO:0000269|PubMed:18529047, ECO:0000269|PubMed:19668192, ECO:0000269|PubMed:19834490, ECO:0000269|PubMed:20080685, ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20705758, ECO:0000269|PubMed:21893193, ECO:0000269|PubMed:25825981, ECO:0000269|PubMed:7929439, ECO:0000269|PubMed:9160888, ECO:0000269|PubMed:9804796, ECO:0000269|PubMed:9837777}.
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
- Approved Drug, UniProt loc high conf, GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Small Molecule Binder
- Other modalities
- Advanced Clinical
gnomAD loss of function constraint: o/e 0.2672699987888336 (upper bound 0.344650000333786). 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 KDR (rivoceranib, pazopanib, ramucirumab, cediranib, tivozanib, axitinib, sorafenib, lenvatinib, midostaurin, cabozantinib s-malate, surufatinib, nintedanib esylate), 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
- Alan HoMemorial Sloan Kettering Cancer Center · 2 of 2 trials Phase 2+
- Anwaar SaeedSWOG Cancer Research Network · 2 of 2 trials Phase 2+
- Dingwei YeFudan University · 2 of 2 trials Phase 2+
- Jessica GartrellSt. Jude Children's Research Hospital · 2 of 2 trials Phase 2+
- Joel W NealECOG-ACRIN Cancer Research Group · 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+
- 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+
- Ze-yang DingTongji Hospital · 2 of 2 trials Phase 2+
- Andrea B ApoloAlliance for Clinical Trials in Oncology · 1 of 2 trials Phase 2+
- Mehmet A BilenEmory University Hospital/Winship Cancer Institute · 1 of 2 trials Phase 2+
- Tapan M KadiaM.D. Anderson Cancer Center · 1 of 2 trials Phase 2+
Registry trials of rivoceranib, pazopanib, ramucirumab, cediranib, tivozanib, axitinib, sorafenib, lenvatinib, midostaurin, cabozantinib s-malate, surufatinib, nintedanib esylate 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; 276 of 376 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. 24 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
382 trials of drugs against KDR were stopped early; 11 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of rivoceranib, pazopanib, ramucirumab, cediranib, tivozanib, axitinib, sorafenib, lenvatinib, midostaurin, cabozantinib s-malate, surufatinib, nintedanib esylate, 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 382.
- suspended · 2026-11-02 · National Cancer Institute (NCI) · Cabozantinib S-malate“Scheduled Interim Monitoring”
- suspended · 2026-10-27 · National Cancer Institute (NCI) · Cabozantinib S-malate“Other - Extend the observation period for current patients”
- 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 · 2026-08-21 · 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 · 2026-08-03 · Hoffmann-La Roche · Ramucirumab“The study was closed because the sponsor decided not to continue the development of certain treatment combinations.”
- terminated · 2026-07-30 · Elevar Therapeutics · Rivoceranib“The RM-202 study was terminated by the Sponsor due to redirection of the rivoceranib development plan.”
- 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 · 2026-06-11 · Changhai Hospital · Surufatinib“This investigator-initiated study closed to recruitment early due to slower-than-anticipated patient accrual.”
- 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 · 2026-06-03 · Genprex, Inc. · ramucirumab“Enrollment was slow, due to competition with the many other clinical trials for the same patient population, which led to the decision to end enrollment in the trial.”
- 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”
- suspended · 2026-03-06 · H. Lee Moffitt Cancer Center and Research Institute · Axitinib“Funding unavailable”
- terminated · 2026-03-05 · Jinling Hospital, China · Lenvatinib“Involving changes to the primary endpoint, it is difficult to unify the evaluation criteria for subjects' endpoints before and after the change.”
- withdrawn · 2026-02-17 · University of Alabama at Birmingham · matched by the registry's drug synonyms“due to overall cost of the study”
- withdrawn · 2026-01-22 · Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico · Pembrolizumab + Lenvatinib“The lack of adequate funding has made it impossible to continue with the clinical study As this study was not initiated, no subject was included and no data was collected,thus no result can be obtained SPONSOR_DECISION End of trial date:15 Oct 2025”
- terminated · 2026-01-13 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“Sponsor Decision”
- terminated · 2026-01-09 · Pfizer · Axitinib“Study was terminated due to portfolio re-prioritization and strategic considerations. The decision was not based on any safety concerns and/or regulatory interactions”
- terminated · 2025-12-17 · John Kirkwood · matched by the registry's drug synonyms“Secura Bio, Inc. discontinued support of the trial.”
Paediatric incentives and obligations for KDR's drugs
For rivoceranib, pazopanib, ramucirumab, cediranib, tivozanib, axitinib, sorafenib, lenvatinib, midostaurin, cabozantinib s-malate, surufatinib, nintedanib esylate: 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 · KDR 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-000780-PIP01-09-M08 (Midostaurin, Treatment of acute myeloid leukaemia;Treatment of malignant mastocytosis;Treatment of mast cell leukaemia): PM: decision on the application for modification of an agreed PIP, 16 Aug 2024; EMEA-002489-PIP02-24 (rivoceranib, Treatment of hepatocellular carcinoma): W: decision granting a waiver in all age groups for all conditions or indications, 14 Jun 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; +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/3/24/2950 positive 25 Jul 2024: Treatment of hepatocellular carcinoma; 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; - negative 23 Sept 2019: Treatment of hepatocellular carcinoma; +12 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 · Sorafenib Accord: authorised since 9 Nov 2022; Kisplyx: authorised since 25 Aug 2016; Lenvima: authorised since 28 May 2015; Cyramza: authorised since 19 Dec 2014; +8 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 rivoceranib, pazopanib, ramucirumab, cediranib, tivozanib, axitinib, sorafenib, lenvatinib, midostaurin, cabozantinib s-malate, surufatinib, nintedanib esylateRule: 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 · 138 interventional studies of rivoceranib, pazopanib, ramucirumab, cediranib, tivozanib, axitinib, sorafenib, lenvatinib, midostaurin, cabozantinib s-malate, surufatinib, nintedanib esylate include patients under 18; 39 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 75 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.