Chemistry:Lirentelimab
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | SIGLEC8 |
| Clinical data | |
| Trade names | AK002 |
| Routes of administration | Intravenous |
| Identifiers | |
| CAS Number | |
| UNII | |
| KEGG | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C6408H9884N1700O2006S46 |
| Molar mass | 144308.221 g·mol−1 |
Lirentelimab (sold under the brand name AK002) is a humanized nonfucosylated monoclonal antibody that targets sialic acid-binding Ig-like lectin 8 (SIGLEC8). In a randomized clinical trial, lirentelimab was found to improve eosinophil counts and symptoms in individuals with eosinophilic gastritis and duodenitis.[2] Adverse reactions include infusion reactions, which are mild to moderate and typically occur following the first infusion.[3]
Mechanism of action
In individuals with asthma, Siglec-8 expression is increased on the surface of eosinophils and mast cells in sputum.[4] Lirentelimab depletes eosinophils via antibody-dependent natural killer cell mediated cytotoxicity.
Pharmacology
Lirentelimab is a humanized, nonfucosylated IgG1 monoclonal antibody that targets Siglec-8.[5] Siglec-8 is an inhibitory receptor present on eosinophils and mast cells, with low level expression on basophils.[2][6] Interleukin-5, granulocyte-macrophage colony stimulating factor, and interleukin-33 enhance anti-Siglec-8 mediated destruction of eosinophils.[6] Lirentelimab inhibits mast cells' IgE-mediated degranulation and de novo synthesis of prostaglandin D2 in vitro.[6]
Adverse events
Mild-to-moderate infusion reactions may occur with lirentelimab, which tend to occur following the first infusion only.[3]
Research
Lirentelimab has been studied for the treatment of chronic spontaneous urticaria, indolent systemic mastocytosis, and severe allergic conjunctivitis.[5]
References
- ↑ "Lirentelimab". KEGG Drug Database. https://www.kegg.jp/entry/D11906.
- ↑ 2.0 2.1 "Anti-Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis". The New England Journal of Medicine 383 (17): 1624–1634. October 2020. doi:10.1056/NEJMoa2012047. PMID 33085861.
- ↑ 3.0 3.1 "Therapeutic antibody effective in eosinophilic gastritis". Healio. October 29, 2019. https://www.healio.com/news/gastroenterology/20191029/therapeutic-antibody-effective-in-eosinophilic-gastritis.
- ↑ "An anti-siglec-8 antibody depletes sputum eosinophils from asthmatic subjects and inhibits lung mast cells". Clinical and Experimental Allergy 50 (8): 904–914. August 2020. doi:10.1111/cea.13681. PMID 32542913.
- ↑ 5.0 5.1 "Current and emerging treatments for chronic spontaneous urticaria". Annals of Allergy, Asthma & Immunology 125 (4): 380–387. October 2020. doi:10.1016/j.anai.2019.08.465. PMID 31494233.
- ↑ 6.0 6.1 6.2 "AK002, a Humanized Sialic Acid-Binding Immunoglobulin-Like Lectin-8 Antibody that Induces Antibody-Dependent Cell-Mediated Cytotoxicity against Human Eosinophils and Inhibits Mast Cell-Mediated Anaphylaxis in Mice". International Archives of Allergy and Immunology 180 (2): 91–102. 2019. doi:10.1159/000501637. PMID 31401630.
External links
- "Lirentelimab". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/Lirentelimab.
 |  |
