| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Humanized (frommouse) |
| Target | IGF-1 receptor |
| Clinical data | |
| ATC code |
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| Identifiers | |
| CAS Number | |
| ChemSpider |
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| UNII | |
| KEGG | |
| ECHA InfoCard | 100.205.569 |
| Chemical and physical data | |
| Formula | C6528H10086N1730O2018S40 |
| Molar mass | 146374.99 g·mol−1 |
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Dalotuzumab is an anti-IGF1 receptor (IGF1R) humanizedmonoclonal antibody designed for the potential treatment of variouscancers.[1] Common adverse effects includehyperglycemia,nausea,vomiting, andfatigue.[2] Dalotuzumab was developed byMerck and Co., Inc.[3]
Dalotuzumab is indicated to treatbreast cancer,colorectal cancer,multiple myeloma,neuroendocrine tumors,non-small cell lung cancer (NSCLC),pancreatic cancer, andsolid tumors.[1]
Adverse effects of Dalotuzumab:[1][2][4]
Insulin-like growth factors (IGFs) are pivotal in cellular processes contributing to normal physiology as well as certain pathologies (e.g.,cancer).[3] The IGF family of proteins, also known as the IGF axis, consists of threeligands (insulin,IGF1,IGF2), three cell surface receptors (insulin receptor [IR],IGF1 receptor [IGF1R],IGF2 receptor [IGF2R]), and sevenIGF binding proteins (IGFBP1-7).[5] Notably, IGF1R serves as the primary receptor within the IGF axis.[5] The IGF1R is areceptor tyrosine kinase (RTK) with aheterotetrameric structure composed of twoextracellular α subunits and twotransmembrane β subunits.[3][5] Upon ligand-induced activation of this receptor,cytoplasmicadaptor proteins, Src-homology collagen (Shc) and insulin receptor substrate (IRS), arephosphorylated and, in turn, trigger the activation of the Ras/Raf/MEK/Erk and phosphoinositide 3-kinase (PI3K)/Akt signaling pathways, respectively.[3] These signaling pathways are involved in the regulation of cell survival andcell cycle progression.[3]
Furthermore,IGF1R amplification and overexpression have been observed in the formation oftumors andmetastasis of various humancancers.[5] These findings justified the development of anti-IGF1R therapies with the goal of inhibiting aberrant receptor activity and potentially yielding anticancer effects.[3] Among said therapies, Dalotuzumab, a humanizedmonoclonal antibody, was designed to target and bind theextracellular domains ofIGF1R, effectively blocking ligand activation of the receptor and preventing downstream signaling.[3] Moreover, the binding of Dalotuzumab toIGF1R, as seen with other anti-IGF1R antibodies,downregulates the expression of the receptors by prompting the internalization and degradation ofIGF1R.[3]
There are more than 30 different anti-IGF1R candidate drugs involved in over 70 industry and academic-initiatedclinical trials.[6]
Dalotuzumab (MK-0646) was developed byMerck and Co., Inc. under license from French pharmaceutical company,Pierre Fabre.[3] Dalotuzumab presently remains inclinical trials and has not been grantedFDA approval.[7]
