Insulin-like Growth Factor(IGF)Family

Insulin-like growth factor (IGF) is a group of growth hormones that play a key role in regulating the signaling processes critical to cell proliferation, differentiation, and survival. These growth factors are expressed in various tissues and cell types, with autocrine, paracrine and endocrine functions. There are two types of IGFs, type I(IGF-I) and type II (IGF-II), act by binding to their specific membrane receptors: IGF-I R and IGF-II R.

As with IGF, IGF receptors are also potential targets for targeted therapies. IGF-I R is a heterotetrameric transmembrane protein with two disulfide-linked alpha subunits and two transmembrane beta subunits. Activation of this pathway has been linked to cancer initiation and growth, with many types of tumor cells overexpressing IGF-IR to promote resistance to radiotherapy, chemotherapy and targeted therapies. To overcome this resistance, IGF / IGF-IR targeted therapies have become a viable cancer treatment strategy. Teprotumumab, a representative drug targeting IGF-IR, was approved by the US Food and Drug Administration (FDA) in 2020 for the treatment of thyroid-associated ophthalmopathy (TAO). Initial studies suggest that combined targeting of IGF-IR and STAT3 may inhibit tumor metastasis and overcome resistance to STAT3-mediated anti-IGF-IR therapy, maximizing the efficacy of cancer treatment.

Schematic diagram of IGF-targeted drugs

Schematic diagram of IGF-targeted drugs

https://doi.org/10.1016/j.gendis.2022.03.002
Therapeutic strategies to inhibit IGF-IR signaling

Therapeutic strategies to inhibit IGF-IR signaling

https://doi.org/10.3390/ijms231911781

ACROBiosystems has developed a series of HEK293-expressed IGF and IGF receptor family proteins, including IGF-IR tetrameric protein, IGF-I, IGF-II, IGFBP-3, IGFBP-4 and IGFBP-7. The IGF family proteins are available in various species and tags, with high purity and high structural homogeneity verified by SDS-PAGE/SEC-MALS. High bioactivity was also validated by ELISA/SPR. Our proteins also undergo a strict quality control system to ensure stable performance in immunization, antibody drug screening and characterization studies to help drug development targeting IGF.

PRODUCT LIST

IGF-I R / IGF-1 R
IGF-I
IGF-II
IGF-II R
IGFBP-1
IGFBP-2
IGFBP-3
IGFBP-3 R
IGFBP-4
IGFBP-5
IGFBP-6
IGFBP-7

Verification Data

High purity and structural homogeneity verified by SDS-PAGE and SEC-MALS
IGR-H5229

The purity of Human IGF-I R, His Tag (Cat. No. IGR-H5229) is more than 90% and the molecular weight of this protein is around 252-308 kDa verified by SEC-MALS.

High biological activity verified by ELISA

IGR-H5229

Immobilized Human IGF-I R, His Tag (Cat. No. IGR-H5229) at 5 μg/mL (100 μL/well) can bind Human IGF-I Protein, Fc Tag (Cat. No. IG1-H5263) with a linear range of 0.01-0.156 μg/mL (Routinely tested).

IGR-H5229

Immobilized Human IGF-I R, His Tag (Cat. No. IGR-H5229) at 5 μg/mL (100 μL/well) can bind Biotinylated Human IGF-I, Avitag,Fc Tag (Cat. No. IG1-H82F7) with a linear range of 0.02-0.625 μg/mL (QC tested).

High biological activity verified by SPR

IL1-H82E8

Human IGFBP-7, His Tag (Cat. No. IG7-H5240) immobilized on CM5 Chip can bind Human C1q R1, His Tag (Cat. No. C11-H5228) with an affinity constant of 16.7 μM as determined in a SPR assay (Biacore 8K) (Routinely tested).

IL3-H82E5

Human IGF-I R, His Tag (Cat. No. IGR-H5229) immobilized on CM5 Chip can bind Biotinylated Human IGF-I, His,Avitag (Cat. No. IG1-H82Q6) with an affinity constant of 68 nM as determined in a SPR assay (Biacore 8K) .

FAQ

Q

Why is structural integrity of recombinant tetrameric IGF-1R important for antibody and ligand-inhibitor screening?

Physiological IGF-1R is a disulfide-linked α2β2 receptor, and its ligand-binding site depends on coordinated extracellular domains. A recombinant soluble tetrameric format can better preserve multivalent extracellular architecture than an isolated domain, but it does not reproduce the transmembrane environment or intracellular kinase function. Incorrect assembly, aggregation, or free subunits may alter ligand binding and antibody epitopes. Molecular-state data and validated IGF binding are therefore important for selecting a screening reagent.
Q

Why should IGF-I, IGF-II, IGF-1R, and IGF-II R be evaluated separately?

IGF-I and IGF-II can both activate IGF-1R, but their availability and receptor interactions differ. IGF-1R is a signaling receptor that promotes growth and survival, whereas IGF-II R mainly regulates IGF-II uptake and turnover rather than functioning as an equivalent signaling receptor. Separate testing helps determine whether a candidate neutralizes one ligand, blocks IGF-1R activation, or changes IGF-II availability through IGF-II R.
Q

Why should IGF-binding proteins be included in IGF-pathway drug screening?

IGF-binding proteins regulate ligand stability, distribution, and the concentration of free IGF available to receptors. A candidate that appears potent in a simplified IGF–IGF-1R assay may behave differently when IGFBPs compete for ligand or alter its presentation. Including relevant IGFBPs can reveal whether an antibody, ligand trap, or engineered receptor remains effective in a more physiologically regulated environment and can clarify the mechanism behind changes in apparent potency.
Q

How do ligand-neutralizing and IGF-1R-targeted strategies differ in pathway coverage?

Ligand-neutralizing approaches can be designed to block IGF-I, IGF-II, or both, while preserving receptor responses to unblocked ligands. IGF-1R-targeted antibodies or inhibitors act at the receptor level and may provide broader pathway suppression, but they can also affect a wider range of normal IGF functions.
Q

Which quality and activity data should be reviewed for IGF-pathway proteins?

For complex receptors such as IGF-1R, useful evidence includes purity, molecular weight, complex homogeneity, and direct ligand-binding activity. SEC-MALS can help identify the molecular state of selected products, while ELISA or SPR confirms interaction with IGF-I or IGF-II. Ligands and IGFBPs may require different qualification packages. Lot-specific specifications should be confirmed before use.

References

  • [1] Wang P, Mak V C Y, Cheung L W T. Drugging IGF-1R in cancer: new insights and emerging opportunities[J]. Genes & Diseases, 2022.https://doi.org/10.1016/j.gendis.2022.03.002.

  • [2] Lin S L, Lin C Y, Lee W, et al. Mini Review: Molecular Interpretation of the IGF/IGF-1R Axis in Cancer Treatment and Stem Cells-Based Therapy in Regenerative Medicine[J]. International Journal of Molecular Sciences, 2022, 23(19): 11781.https://doi.org/10.3390/ijms231911781.

  • [3] Morrione A, Belfiore A. Obesity, Diabetes, and Cancer: The Role of the Insulin/IGF Axis; Mechanisms and Clinical Implications[J]. Biomolecules, 2022, 12(5): 612.https://doi.org/10.3390/biom12050612.

  • Introduction
  • PRODUCT LIST
  • Verification Data
  • FAQ
  • References