IGF-1R

The insulin-like growth factor 1 receptor (IGF1R) is a cell-surface tyrosine kinase receptor that is synthesized as a single polypeptide chain which is then processed to yield an around 180-kDa glycopeptide. The IGF1R is involved in growth, development, and differentiation processes. The IGF1R displays a very strong antiapoptotic activity and protects IGF1R-expressing cells from programmed cell death.

1001350-96-4
BMS-754807
1001350-96-4
1054315-48-8
BMS695735
1054315-48-8
1089283-49-7
GSK-1904529a
1089283-49-7
196868-63-0
PQ 401
196868-63-0
NBI 31772
374620-70-9
468740-43-4
BMS-536924
468740-43-4
475488-23-4
ADW742
475488-23-4
475489-16-8
AEW-541
475489-16-8
477-47-4
Picropodophyllin
477-47-4
B0084-186154
Sunitinib
557795-19-4
65678-07-1
AG-1024
65678-07-1
78860-34-1
867160-71-2
Linsitinib
867160-71-2

Background


An overview of IGF-1R

The type 1 insulin kike growth factor receptor (IGF-1R) is glycoprotein, a member of the tyrosine protein kinase family, and consists of two disulfide-linked α-chains that bind IGF-1 and IGF-2 and two β-chains that include a tyrosine kinase domain and a transmembrane. A conformational change is induced by high-affinity binding of IGF-1 or IGF-2 to the IGF-1R extracellular domain, resulting in autophosphorylation of intracellular tyrosine residues. In 1989, scientists at the University of Vanderbilt found that monoclonal antibodies to IGF-1R inhibited tumor growth in mice.

Inhibition of IGF-1R

As the first cloned tyrosine protein kinase, IGF-1R has become a hot target for lots of pharmaceutical companies. In some cells, IGF-1R can induce signal transduction and phosphorylate transcription-activated protein activators, inhibiting cell proliferation and apoptosis. In addition, IGF-1R signal transduction can also cause cell malignancy and change cell adhesion. Therefore, IGF-1R is considered to be an effective target for tumor treatment. According to reports, IGF-1R monoclonal antibodies, small molecule kinase inhibitors, antisense oligonucleotides and dominant negative mutants are all effective in preclinical trials with extremely low toxicity. The vast expression of IGF-1R in cancer cells makes it easy to figure out variety of approaches to targeting IGF-1R. For example, it may be a good idea to block IG-1R signaling by interfering with receptor synthesis and expression. Developing selective small molecular inhibitors can also interrupt IGF-1R activity.

IGF-1R and diseases

In the 1980s, scientists found that most tumors displayed enhanced IGF-1R concentrations and expressed high IGF-1R mRNA levels, which is proved by clinical and experimental studies. From then on, an increasing number of evidence indicates a crucial role of IGR-1R in development and progression of cancer, resulting in an overgeneralization that IGF-1R is equal to malignancy. Clinical experimental results showed that IGF-1R inhibitor combined with traditional chemoradiotherapy could enhance the effect of anti-tumor. For continuing anti IGF-1R therapies, a better understanding of these cases can contribute to the treatment of cancer.

References:

1. Farabaugh, S. M., Boone, D. N. & Lee, A. V. Role of IGF1R in breast cancer subtypes, sternness, and lineage differentiation. Frontiers in Endocrinology 6, 2015.00059 (2015).

2. Werner, H. Tumor suppressors govern insulin-like growth factor signaling pathways: implications in metabolism and cancer. Oncogene 31, 2703-2714.2011.447 (2012).

3. Mountzios, G. et al. Insulin-Like Growth Factor 1 Receptor (IGF1R) Expression and Survival in Operable Squamous-Cell Laryngeal Cancer. PLoS One 8,.0054048 (2013).

4. Xu Y, Wang G S, Sun W, et al. Progress in the studies on small molecule IGF-1R inhibitors. Acta Pharmaceutica Sinica, 43(10):979.(2008).