Synonyms: AMY-109 | H1009/L395-F1974m [2]
Compound class:
Antibody
Comment: AMY109 is a long-acting monoclonal antibody that blocks IL-8 recycling [4]. It was designed to reduce levels of IL-8 in endometriosis lesions, in which excessive IL-8 has been identified as a driving factor in promoting inflammation and fibrosis [1,3,5]. AMY109 is proposed as a potential disease-modifying treatment for endometriosis.
AMY109 is engineered to bind IL-8 in a pH-dependent manner. In the acidic conditions within the endosome, the antibody-IL-8 mmune complex dissociates; the free antibody is re-cycled and the IL-8 is trafficked to the lysosome for degradation. |
References |
1. Beste MT, Pfäffle-Doyle N, Prentice EA, Morris SN, Lauffenburger DA, Isaacson KB, Griffith LG. (2014)
Molecular network analysis of endometriosis reveals a role for c-Jun-regulated macrophage activation. Sci Transl Med, 6 (222): 222ra16. [PMID:24500404] |
2. Kakiuchi A, Kato A, Hatashi S, Yanagisawa I, Konn R, Netsu S, Sankai T. (2018)
Composition for prophylaxis or treatment of il-8 related diseases. Patent number: WO2018025982A1. Assignee: Chugai Pharmaceutical Co Ltd Jichi Medical University National Institutes of Biomedical Innovation Health and Nutrition. Priority date: 04/08/2017. Publication date: 08/02/2018. |
3. Konno R, Yamada-Okabe H, Fujiwara H, Uchiide I, Shibahara H, Ohwada M, Ihara T, Sugamata M, Suzuki M. (2003)
Role of immunoreactions and mast cells in pathogenesis of human endometriosis--morphologic study and gene expression analysis. Hum Cell, 16 (3): 141-9. [PMID:15005245] |
4. Nishimoto-Kakiuchi A, Sato I, Nakano K, Ohmori H, Kayukawa Y, Tanimura H, Yamamoto S, Sakamoto Y, Nakamura G, Maeda A et al.. (2023)
A long-acting anti-IL-8 antibody improves inflammation and fibrosis in endometriosis. Sci Transl Med, 15 (684): eabq5858. [PMID:36812343] |
5. Sikora J, Smycz-Kubańska M, Mielczarek-Palacz A, Kondera-Anasz Z. (2017)
Abnormal peritoneal regulation of chemokine activation-The role of IL-8 in pathogenesis of endometriosis. Am J Reprod Immunol, 77 (4). [PMID:28120482] |