INSR insulin receptor
ENSG00000171105 · protein coding · Open Targets profile
Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras- MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin- stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. In adipocytes, inhibits lipolysis (By similarity). {ECO:0000250|UniProtKB:P15208, ECO:0000269|PubMed:12138094, ECO:0000269|PubMed:16314505, ECO:0000269|PubMed:16831875, ECO:0000269|PubMed:8257688, ECO:0000269|PubMed:8276809, ECO:0000269|PubMed:8452530, ECO:0000269|PubMed:9428692}.
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
- Advanced Clinical, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- Antibody
- GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM, Human Protein Atlas loc
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 0.46983999013900757 (upper bound 0.5757799744606018). 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 111 registry trials, updated in the last three years, of the most advanced drugs against INSR (insulin susp isophane recombinant human, insulin purified beef, insulin pork, insulin purified pork, insulin zinc susp recombinant human, insulin degludec, insulin detemir, insulin icodec, insulin glulisine, insulin peglispro, linsitinib, insulin human, isophane), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Kevin KaisermanMannkind Corporation · 3 of 3 trials Phase 2+
- Chunyue HaoGan & Lee Pharmaceuticals. · 2 of 2 trials Phase 2+
- Kartik VenkateshOhio State University · 2 of 2 trials Phase 2+
- Agnieszka SzypowskaDepartment of Pediatrics, Medical University of Warsaw · 1 of 1 trials Phase 2+
- Antoinette MoranUniversity of Minnesota · 1 of 1 trials Phase 2+
- Antonino TuttolomondoUniversity of Palermo · 1 of 1 trials Phase 2+
- Arthi ThirumalaiUniversity of Washington · 1 of 1 trials Phase 2+
- Irl B. HirschUniversity of Washington · 1 of 1 trials Phase 2+
- Jamie HI TeohHospital Pulau Pinang, Malaysis · 1 of 1 trials Phase 2+
- Joana Lopes PerdigaoLoyola University · 1 of 1 trials Phase 2+
- Kevin PantaloneStaff · 1 of 1 trials Phase 2+
- Maya FayfmanEmory University · 1 of 1 trials Phase 2+
- Monica AlvesState University of Campinas (Unicamp) · 1 of 1 trials Phase 2+
- Nabila RekikSTEDIAM · 1 of 1 trials Phase 2+
- Nitesh D KuhadiyaUniversity at Buffalo · 1 of 1 trials Phase 2+
Registry trials of insulin susp isophane recombinant human, insulin purified beef, insulin pork, insulin purified pork, insulin zinc susp recombinant human, insulin degludec, insulin detemir, insulin icodec, insulin glulisine, insulin peglispro, linsitinib, insulin human, isophane 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; 74 of 106 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.
57 trials of drugs against INSR were stopped early; 11 give no reason
Terminated, withdrawn and suspended interventional trials of insulin susp isophane recombinant human, insulin purified beef, insulin pork, insulin purified pork, insulin zinc susp recombinant human, insulin degludec, insulin detemir, insulin icodec, insulin glulisine, insulin peglispro, linsitinib, insulin human, isophane, 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.
- terminated · 2026-11-05 · University of Campinas, Brazil · matched by the registry's drug synonyms“Enrollment closed before the planned 36 eyes were reached because of the limited number of eligible patients and the long recruitment period (July 2024 to December 2025); 20 eyes of 19 participants were enrolled.”
- terminated · 2026-08-31 · Emory University · matched by the registry's drug synonyms“The study was suspended and during this time recruitment and study activities were halted. The study was ultimately terminated in April 2026 without having re-opened for recruitment additional participants.”
- terminated · 2025-09-08 · Sanofi · Insulin degludec 100 U/mL“Sponsor decision to cancel trial due to poor recruitment/ severe recruitment delay and not related to safety concern.”
- terminated · 2025-03-17 · University of Minnesota · matched by the registry's drug synonymsNo reason given
- terminated · 2024-11-20 · Astellas Pharma Inc · matched by the registry's drug synonyms“Company decided not to pursue the development of this drug in this patient population at this time”
- terminated · 2024-02-21 · Centre Hospitalier Universitaire Dijon · matched by the registry's drug synonyms“recruitment difficulties”
- terminated · 2023-11-02 · Charles Drew University of Medicine and Science · matched by the registry's drug synonymsNo reason given
- terminated · 2023-08-14 · Novo Nordisk A/S · insulin detemir“See termination reason in detailed description”
- terminated · 2022-07-26 · Inova Health Care Services · matched by the registry's drug synonyms“Blood sugar status of the enrolled subjects wasn't evaluable”
- terminated · 2022-04-07 · Sanofi · matched by the registry's drug synonyms“Due to "prolonged low participant recruitment"”
- terminated · 2021-05-17 · Hennepin Healthcare Research Institute · matched by the registry's drug synonyms“Enrollment was too low to provide statistically significant data”
- terminated · 2020-09-11 · Northwestern University · matched by the registry's drug synonyms“Unable to recruit sufficient number of patients”
- terminated · 2020-06-09 · Weill Cornell Medical College in Qatar · Insulin Degludec U100“The study was terminated by the IRB and the Institutional Official after the MOPH and WCMQ audits”
- terminated · 2020-04-09 · HealthPartners Institute · Insulin glulisine“Study will not have power to show a difference between groups.”
- withdrawn · 2020-03-10 · Providence Health & Services · matched by the registry's drug synonymsNo reason given
- terminated · 2019-10-11 · University of Texas Southwestern Medical Center · Insulin detemir“Presumed loss of clinical equipoise between the agents being investigated”
- withdrawn · 2019-07-23 · Institut de Recherches Cliniques de Montreal · matched by the registry's drug synonymsNo reason given
- withdrawn · 2019-01-16 · University of Texas Southwestern Medical Center · matched by the registry's drug synonymsNo reason given
- terminated · 2018-09-13 · University Health Network, Toronto · matched by the registry's drug synonyms“The Sponsor decided to stop further manufacture the study drug 'Linsitinib' in Nov 2015.”
- terminated · 2018-09-10 · Novo Nordisk A/S · Insulin detemirNo reason given
- terminated · 2018-09-05 · Novo Nordisk A/S · insulin detemir“See termination reason in detailed description”
- terminated · 2018-08-27 · University Hospital, Strasbourg, France · matched by the registry's drug synonymsNo reason given
- terminated · 2018-04-12 · Nationwide Children's Hospital · insulin detemir [rDNA origin] injection“PI left the institution”
- withdrawn · 2018-01-31 · Institut de Recherches Cliniques de Montreal · matched by the registry's drug synonyms“Medtronic support terminated”
- terminated · 2017-11-21 · Emory University · matched by the registry's drug synonyms“safety issue observed on another hepatocellular study using OSI906”
Paediatric incentives and obligations for INSR's drugs
For insulin susp isophane recombinant human, insulin purified beef, insulin pork, insulin purified pork, insulin zinc susp recombinant human, insulin degludec, insulin detemir, insulin icodec, insulin glulisine, insulin peglispro, linsitinib, insulin human, isophane: 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 · INSR 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-002988-PIP01-21 (insulin icodec;semaglutide, Treatment of type II diabetes mellitus): W: decision granting a waiver in all age groups for all conditions or indications, 11 Aug 2021; EMEA-001097-PIP01-10-M02 (Insulin peglispro, Treatment of type I diabetes mellitus;Treatment of type II diabetes mellitus): PM: decision on the application for modification of an agreed PIP, 8 Jul 2014; EMEA-000479-PIP01-08-M03 (insulin degludec;insulin aspart, Treatment of type I diabetes mellitus;Treatment of type II diabetes mellitus): PM: decision on the application for modification of an agreed PIP, 6 Mar 2015; compliance positive 11 Sept 2015; EMEA-000412-PIP01-08-M01 (Insulin detemir, Treatment of type II diabetes mellitus;Treatment of type I diabetes mellitus): PM: decision on the application for modification of an agreed PIP, 11 Jul 2014; compliance positive 14 Nov 2014; +2 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/3/12/977 withdrawn 2 Apr 2012: Treatment of adrenal cortical 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/3/12/977, 2026-11-11
- Authorised in the EU: yes · Apidra: authorised since 27 Sept 2004; Kyinsu: authorised since 24 Nov 2025; Awiqli: authorised since 17 May 2024; Tresiba: authorised since 20 Jan 2013; +3 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 insulin susp isophane recombinant human, insulin purified beef, insulin pork, insulin purified pork, insulin zinc susp recombinant human, insulin degludec, insulin detemir, insulin icodec, insulin glulisine, insulin peglispro, linsitinib, insulin human, isophaneRule: 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 · 66 interventional studies of insulin susp isophane recombinant human, insulin purified beef, insulin pork, insulin purified pork, insulin zinc susp recombinant human, insulin degludec, insulin detemir, insulin icodec, insulin glulisine, insulin peglispro, linsitinib, insulin human, isophane include patients under 18; 0 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 21 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.