Insulin-like growth factor II

Summary

Insulin-like growth factor II (IGF-2) is an endogenous 67-amino-acid peptide hormone encoded by the IGF2 gene on chromosome 11p15.5. It is primarily expressed during fetal development, where it plays a critical role in fetal growth and organogenesis. IGF-2 signals through IGF-1R and IR-A to drive mitogenic and metabolic effects. It is implicated in several cancers (Wilms tumor, colorectal, breast, hepatocellular) due to loss of imprinting. As an exogenous therapeutic, IGF-2 remains in research stages with no approved clinical indications.

Mechanism of Action

Binds primarily to the IGF-1 receptor (IGF-1R) and insulin receptor isoform A (IR-A), activating PI3K/AKT and MAPK/ERK signaling pathways to promote cell proliferation, differentiation, survival, and fetal growth. Also binds the IGF-2 receptor (mannose-6-phosphate receptor), which acts as a clearance receptor limiting circulating IGF-2 levels.

Routes of Administration

Goals & Uses

• Metabolic regulation / insulin sensitizationMetabolismLow
• Neuroprotection and cognitive functionNeurologyLow
• Oncology biomarker / cancer driver understandingOncology / ResearchModerate
• Fetal and neonatal growth supportEndocrinology / GrowthLow
• Muscle regeneration and repairMusculoskeletalLow

Contraindications

• Active malignancyOncologyHighUse caution or avoid depending on agent and context
• Diabetic retinopathyOphthalmologyModerate
• Acromegaly or gigantismEndocrineHigh
• Hypoglycemia risk / insulin-secreting tumorsEndocrinologyHigh

Adverse Effects

• EdemaFluid BalanceUncommonSwelling from fluid retention
• HypoglycemiaMetabolicCommonAbnormally low blood glucose
• Injection site reactionsLocalCommon
• Tumor growth promotionOncologyUnknown
• Headache and intracranial hypertensionNeurologicalUncommon

Drug Interactions

• Insulin and insulin secretagoguesHigh
• CorticosteroidsModerate
• Anticancer / anti-IGF therapies (e.g., figitumumab, ganitumab)High
• Growth hormoneModerate

Population Constraints

• Pediatric patientsAgeRelative
• Patients with Beckwith-Wiedemann syndromeGeneticAbsolute
• Elderly patientsAgeRelative
• Pregnant womenReproductiveRelative
• Patients with personal or family history of cancerOncology RiskRelative

Regulatory Status

• European UnionUnapprovedEMA has not approved IGF-2 as a therapeutic agent. No marketing authorization exists.
• United StatesUnapprovedIGF-2 is not approved by the FDA for any therapeutic indication. It is available only as a research reagent.
• United KingdomUnapprovedMHRA has not approved IGF-2 for clinical use. Status mirrors EU/US as a research-only compound.

IGF-2 is not approved as a therapeutic agent by the FDA, EMA, or any major regulatory authority. It is used in research and preclinical settings. Related compounds (e.g., mecasermin/IGF-1) have received approval for other indications, but IGF-2 itself has no approved therapeutic application.

Evidence & Sources

No sources recorded yet.