Last update 21 Mar 2024
Siglec-8
Sialic acid-binding Ig-like lectin 8
Last update 21 Mar 2024
Basic Info
Synonyms MGC59785, SAF-2, SAF2 + [7] |
Introduction Putative adhesion molecule that mediates sialic-acid dependent binding to red blood cells (PubMed:10856141, PubMed:10625619). Preferentially binds to alpha-2,3-linked sialic acid. Also binds to alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface (PubMed:10625619). Recognizes simultaneously epitopes having a terminal N-acetylneuraminic acid (sialic acid) and an underlying 6-O-sulfated galactose. Preferentially binds to Gal-6-sulfated sialyl-Lewis X glycan epitopes (PubMed:27357658). |
Related
Target |
Mechanism |
Active Org. |
Originator Org. |
Active Indication |
Inactive Indication |
Drug Highest Phase |
First Approval Ctry. / Loc. |
First Approval Date |
Target |
Mechanism |
Active Org. |
Originator Org. |
Active Indication |
Inactive Indication |
Drug Highest Phase |
First Approval Ctry. / Loc. |
First Approval Date |
Target |
Mechanism |
Active Org. |
Originator Org. |
Active Indication |
Inactive Indication |
Drug Highest Phase |
First Approval Ctry. / Loc. |
First Approval Date |
A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Lirentelimab in Adult Subjects With H-1 Antihistamine Refractory Chronic Spontaneous Urticaria
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Subcutaneous Lirentelimab in Adult Subjects With Moderate-to-Severe Atopic Dermatitis Inadequately Controlled by Topical Treatments
A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamic Effect of Subcutaneous AK002 in Subjects With Moderate to Severe Eosinophilic Gastritis and/or Eosinophilic Duodenitis
100 Clinical Results associated with Siglec-8
Login to view more data
100 Translational Medicine associated with Siglec-8
Login to view more data
Login to view more data
13 Jan 2024Current allergy and asthma reports
Mast Cell-Targeting Therapies in Mast Cell Activation Syndromes.
Review
Author: Vito Sabato ; Michiel Beyens ; Alessandro Toscano ; Athina Van Gasse ; Didier G Ebo
PURPOSE OF REVIEW:
Provide an overview of the expanding landscape of mast cell (MC)-targeting treatments in mast cell activation syndromes (MCAS).
RECENT FINDINGS:
Tyrosine-kinase inhibitors (TKIs) targeting wild-type and mutated KIT can efficiently induce MC depletion. Avapritinib and midostaurin can also temper IgE-mediated degranulation. Avapritinib has been recently approved by the FDA for the treatment of indolent systemic mastocytosis (ISM). Targeting activation pathways and inhibitory receptors is a promising therapeutic frontier. Recently, the anti Siglec-8 antibody lirentelimab showed promising results in ISM. MCAS is a heterogeneous disorder demanding a personalized therapeutic approach and, especially when presenting as anaphylaxis, has not been formally captured as outcome in prospective clinical trials with TKI. Long-term safety of TKI needs to be addressed. New drugs under investigation in diseases in which non-neoplastic MCs play a pivotal role can provide important inputs to identify new efficient and safe treatments for MCAS.
07 Jan 2024Allergy
Regulation of mast cells by overlapping but distinct protein interactions of Siglec-6 and Siglec-8.
Article
Author: Wouter Korver ; Zachary Benet ; Alan Wong ; Gian Luca Negri ; Katherine Chang ; Robert Sanchez ; John Leung ; Naomi De Freitas ; Thuy Luu ; Julia Schanin ; Bradford A Youngblood
BACKGROUND:
Sialic acid-binding immunoglobulin-like lectin (Siglec)-6 and Siglec-8 are closely related mast cell (MC) receptors with broad inhibitory activity, but whose functional differences are incompletely understood.
METHODS:
Proteomic profiling using quantitative mass spectrometry was performed on primary mouse MCs to identify proteins associated with Siglec-6 and Siglec-8. For functional characterization, each receptor was evaluated biochemically and in ex vivo and in vivo inhibition models of IgE and non-IgE-mediated MC activation in Siglec-6- or Siglec-8-expressing transgenic mice.
RESULTS:
Siglec-6 and Siglec-8 were found in MCs within large complexes, interacting with 66 and 86 proteins, respectively. Strikingly, Siglec-6 and Siglec-8 interacted with a large cluster of proteins involved in IgE and non-IgE-mediated MC activation, including the high affinity IgE receptor, stem cell factor (SCF) receptor KIT/CD117, IL-4 and IL-33 receptors, and intracellular kinases LYN and JAK1. Protein interaction networks revealed Siglec-6 and Siglec-8 had overlapping yet distinct MC functions, with a potentially broader regulatory role for Siglec-6. Indeed, Siglec-6 preferentially interacted with the mature form of KIT at the cell surface, and treatment with an anti-Siglec-6 antibody significantly inhibited SCF-mediated MC activation more in comparison to targeting Siglec-8.
CONCLUSION:
These data demonstrate a central role for Siglec-6 and Siglec-8 in controlling MC activation through interactions with multiple activating receptors and key signaling molecules. Our findings suggest that Siglec-6 has a role distinct from that of Siglec-8 in regulating MC function and represents a distinct potential therapeutic target in mast cell-driven diseases.
09 Nov 2023Angewandte Chemie (International ed. in English)
Tetra- and Hexavalent Siglec-8 Ligands Modulate Immune Cell Activation.
Article
Author: Gabriele Conti ; Anne Bärenwaldt ; Said Rabbani ; Mirza Sarcevic ; Xiaohua Jiang ; Oliver Schwardt ; Daniel Ricklin ; Roland J Pieters ; Heinz Läubli ; Beat Ernst ; Tobias Mühlethaler
Carbohydrate-binding proteins are generally characterized by poor affinities for their natural glycan ligands, predominantly due to the shallow and solvent-exposed binding sites. To overcome this drawback, nature has exploited multivalency to strengthen the binding by establishing multiple interactions simultaneously. The development of oligovalent structures frequently proved to be successful, not only for proteins with multiple binding sites, but also for proteins that possess a single recognition domain. Here we present the syntheses of a number of oligovalent ligands for Siglec-8, a monomeric I-type lectin found on eosinophils and mast cells, alongside the thermodynamic characterization of their binding. While the enthalpic contribution of each binding epitope was within a narrow range to the one of the monomeric ligand, the entropy penalty increases steadily with growing valency. Additionally, we observed a successful agonistic binding of the tetra- and hexavalent and, to an even larger extent, multivalent ligands to Siglec-8 on immune cells and modulation of immune cell activation. Thus, triggering a biological effect is not restricted to multivalent ligands but could be induced by low oligovalent ligands as well, whereas a monovalent ligand, despite binding with similar affinity, showed an antagonistic effect.
12 Feb 2024
ImmunotherapyPhase 1
16 Jan 2024
Phase 2Clinical ResultClinical Trial Failure
16 Jan 2024
Clinical ResultPhase 2Phase 1
Analysis
Perform a panoramic analysis of this field.
login
or
Get started for free today!
Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.
Start your data trial now!
Synapse data is also accessible to external entities via APIs or data packages. Leverages most recent intelligence information, enabling fullest potential.
Bio
Bio Sequences Search & Analysis
Sign up for free
Chemical
Chemical Structures Search & Analysis
Sign up for free