Figitumumab Overview

Introduction of Figitumumab

Figitumumab (CP-751, 871, CP), a human anti-IGF-IR monoclonal antibody (mAb), is proved to have antiproliferation and anti-tumorigenicity effects in cancer cells and xenografted mice, and it has been showed to be effective in combination with other cytotoxic agents to target many cancer types. This drug was being developed by Pfizer, but they ceased development of the drug in January 2011 and had stopped its manufacture. CP was investigated in a Phase II clinical trial in combination with etoposide and cisplatin as a first-line treatment for extensive stage SCLC (NCT00977561). However this trial was prematurely terminated on 2011 due to slow enrollment of patients. Figitumumab has been used in trials studying the treatment of Sarcoma, Solid Tumor, Breast Cancer, Lung Neoplasms, and Advanced Cancer, among others.

Mechanism of Action of Figitumumab

The insulin family of growth factors is an evolutionally conserved system which plays a crucial role in the growth and development of many tissues and the regulation of overall growth and metabolism. This system comprises three receptors [insulin receptor (IR), IGF-1 receptor (IGF-1R), and IGF-2/mannose 6-phosphate receptor (M-6-PR)], three ligands (insulin, IGF-1, and IGF-2), and six known types of circulating IGF-binding proteins (IGFBP1-6). The IGF-1R is highly homologous to the IR.

The IGF-1R is a receptor tyrosine kinase with a structure of a heterotetrameric glycoprotein composed of two α and two β subunits, post-transcriptionally linked by disulfide bonds, which regulates cell survival and cell cycle progression via the PI3K/Akt and extracellular signal regulated kinase pathways through insulin receptor substrate-1to-4 (IRS-1to-4) and Src-homology collagen (Shc) adapter proteins. Phosphorylation of the IRS adapter molecules on one hand triggers activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, whereas, on the other hand, the Shc adapter activates signaling by the Ras/Raf/MEK/Erk signaling pathway. IGF-IR seems to be expressed in most human cancers. The two IGF-1R ligands, IGF-1 and IGF-2, have been implicated in cancer initiation and progression.

In the past decades, a large amount of evidence has emphasized that IGF-IR play a key role in the transformation of cells, cancer cell proliferation, as well as in metastatic events, associated in various types of human cancers. It seems that inhibition of IGF-IR signaling can generate antineoplastic effects. A number of monoclonal antibodies have been developed to target the receptor itself, which bind to the extracellular domains of the IGF-1R and block ligand binding. A feature common to all anti-IGF-1R antibodies, probably more important than the blocking activity itself, is their ability to down-regulate of the IGF-1R overtime by promoting internalization of the receptor. Receptor targeting antibodies might have important therapeutic advantages, concerning both specificity and toxicity. A variety of fully human anti-IGF-1R monoclonal antibodies have been characterized and showed strong anti-tumor activity in vitro and in vivo.

Figitumumab is a highly potent and fully human IgG2 monoclonal antibody against IGF1R. Figitumumab can prevent IGF1and IGF2 from binding to IGF1R, and as a result inhibits IGF1 and IGF2-induced autophosphorylation of IGF1Rand indirectly inhibits AKT activation in preclinical studies. Figitumumab also inhibited xenograft tumor growth via inhibition of IGF signaling, particularly when combined with chemotherapy or endocrine therapy.

Figure 1 Mechanism of Action of Figitumumab

What We Provide

Therapeutic Antibody

Figitumumab

We provide high-quality Figitumumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

For research use only. Not intended for any clinical use.