IGF1R insulin like growth factor 1 receptor
ENSG00000140443 · protein coding · Open Targets profile
Receptor tyrosine kinase which mediates actions of insulin- like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R.
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 Withdrawn means the drug was pulled from the market or from development.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 SigP or TMHMM
- PROTAC
- Literature, UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 0.3043600022792816 (upper bound 0.3913300037384033). 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 59 registry trials, updated in the last three years, of the most advanced drugs against IGF1R (masoprocol, mecasermin, teprotumumab, veligrotug, figitumumab, linsitinib, ganitumab, AXL-1717, istiratumab, dalotuzumab, BMS-754807, robatumumab), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Alexander KolevzonIcahn School of Medicine at Mount Sinai · 1 of 1 trials Phase 2+
- David ShulmanDana-Farber Cancer Institute · 1 of 1 trials Phase 2+
- Gajanathan MuthuvelCincinnati Childrens Hospital Medical Center · 1 of 1 trials Phase 2+
- Laura EssermanUniversity of California, San Francisco · 1 of 1 trials Phase 2+
- Philippe BackeljauwCincinnati Childrens Hospital · 1 of 1 trials Phase 2+
- Principal Investigator - Czech RepublicGeneral Faculty Hospital, Charles University · 1 of 1 trials Phase 2+
- Principal Investigator - ItalyInstituto Europeo de Oncologia · 1 of 1 trials Phase 2+
- Steven G DuBoisChildren's Oncology Group · 1 of 1 trials Phase 2+
- Joseph LudwigM.D. Anderson Cancer Center · 0 of 1 trials Phase 2+
- Leila ShepherdImperial College London · 0 of 1 trials Phase 2+
- Shancheng RenShanghai Changzheng Hospital · 0 of 1 trials Phase 2+
- Tracy ManuckUniversity of North Carolina, Chapel Hill · 0 of 1 trials Phase 2+
- Yi WangPeking University Third Hospital · 0 of 1 trials Phase 2+
Registry trials of masoprocol, mecasermin, teprotumumab, veligrotug, figitumumab, linsitinib, ganitumab, AXL-1717, istiratumab, dalotuzumab, BMS-754807, robatumumab 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; 27 of 52 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. 7 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
57 trials of drugs against IGF1R were stopped early; 7 give no reason
Terminated, withdrawn and suspended interventional trials of masoprocol, mecasermin, teprotumumab, veligrotug, figitumumab, linsitinib, ganitumab, AXL-1717, istiratumab, dalotuzumab, BMS-754807, robatumumab, 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.
- withdrawn · 2026-04-14 · University of California, Los Angeles · matched by the registry's drug synonyms“The sponsor has notified us that they are not funding the study”
- 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 · 2024-11-08 · NantBioScience, Inc. · matched by the registry's drug synonyms“NCT01318642: Planned independent DMC Interim review: ended for futility”
- terminated · 2024-09-25 · NantCell, Inc. · matched by the registry's drug synonyms“Study was closed due to administrative decision”
- terminated · 2024-08-23 · NantCell, Inc. · matched by the registry's drug synonyms“Subjects discontinued study”
- terminated · 2024-08-20 · NantCell, Inc. · matched by the registry's drug synonyms“Sponsor decision - subjects rolled over to protocol 20101116”
- terminated · 2024-08-01 · Dana-Farber Cancer Institute · Ganitumab“The study closed early due to discontinuation of ganitumab supply.”
- terminated · 2024-06-28 · Amgen · matched by the registry's drug synonyms“Poor enrollment”
- terminated · 2024-02-08 · Icahn School of Medicine at Mount Sinai · matched by the registry's drug synonyms“Decision made to terminate due to difficulty in procurement of adequate supply of treatment drug. Decision made on April 2023 to terminate study.”
- terminated · 2023-05-22 · Rush University Medical Center · matched by the registry's drug synonyms“Investigator went to another institution.”
- terminated · 2023-03-30 · Ipsen · Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])“The study was prematurely terminated due to strategic reasons.”
- terminated · 2022-04-14 · National Cancer Institute (NCI) · Ganitumab“The pharmaceutical company discontinued availability of the drug and we were forced to close the study before phase II was completed. Only one participant was enrolled on phase II.”
- terminated · 2020-12-10 · Pfizer · matched by the registry's drug synonyms“Study was withdrawn due to scientific and business considerations.”
- terminated · 2020-08-14 · Ipsen · rh IGF-1 (mecasermin)“Unacceptable frequency of hypoglycemia observed at and above 200 ug/kg/day”
- terminated · 2020-08-11 · Bristol-Myers Squibb · BMS-754807“Business objectives have changed.”
- terminated · 2020-05-04 · Merck Sharp & Dohme LLC · Dalotuzumab“This trial was halted prematurely for business reasons and low enrollment.”
- terminated · 2018-09-13 · Novartis Pharmaceuticals · 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 · 2018-08-27 · Merck Sharp & Dohme LLC · Robatumumab“Study was terminated for business reasons.”
- terminated · 2018-08-24 · Merck Sharp & Dohme LLC · Robatumumab“This study was terminated for business reasons.”
- terminated · 2018-08-23 · Merck Sharp & Dohme LLC · robatumumab“The study was prematurely terminated for strategic reasons, not for a safety concern.”
- terminated · 2018-08-16 · Merck Sharp & Dohme LLC · dalotuzumab“The study was terminated for business reasons and not due to any safety or efficacy concerns related to dalotuzumab.”
- terminated · 2018-03-02 · Nationwide Children's Hospital · matched by the registry's drug synonyms“PI left institution”
- terminated · 2017-11-21 · Emory University · matched by the registry's drug synonyms“safety issue observed on another hepatocellular study using OSI906”
- terminated · 2017-09-05 · Merrimack Pharmaceuticals · matched by the registry's drug synonyms“Sponsor decision”
Paediatric incentives and obligations for IGF1R's drugs
For masoprocol, mecasermin, teprotumumab, veligrotug, figitumumab, linsitinib, ganitumab, AXL-1717, istiratumab, dalotuzumab, BMS-754807, robatumumab: 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: yes · IGF1R is on the list. Membership alone neither requires nor waives a pediatric study.Rule: 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-001973-PIP02-23 (teprotumumab, Treatment of thyroid eye disease): W: decision granting a waiver in all age groups for all conditions or indications, 7 Sept 2023; EMEA-001973-PIP01-16 (teprotumumab, Treatment of active thyroid eye disease): W: decision granting a waiver in all age groups for all conditions or indications, 2 Dec 2016Rule: 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/3/06/373 expired 22 May 2006: Treatment of primary insulin-like growth factor-1 deficiency due to molecular or genetic defects; EU/3/12/977 withdrawn 2 Apr 2012: Treatment of adrenal cortical carcinoma; EU/3/05/307 positive 26 Aug 2005: Treatment of primary growth hormone insensitivity syndromeRule: 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 · Increlex: authorised since 2 Aug 2007, exceptional circumstances; Tepezza: authorised since 19 Jun 2025Rule: 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 masoprocol, mecasermin, teprotumumab, veligrotug, figitumumab, linsitinib, ganitumab, axl-1717, istiratumab, dalotuzumab, bms-754807, robatumumabRule: 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 · 33 interventional studies of masoprocol, mecasermin, teprotumumab, veligrotug, figitumumab, linsitinib, ganitumab, axl-1717, istiratumab, dalotuzumab, bms-754807, robatumumab include patients under 18; 4 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 20 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.