Delving into the Latest Updates on XQ2B with Synapse

Overview

Basic Info

Drug Type

Recombinant polypeptide

Synonyms-

Target

CGAS

Mechanism

CGAS inhibitors(cyclic GMP-AMP synthase inhibitors)

Therapeutic Areas

Infectious Diseases

Active Indication

Herpesviridae Infections

Inactive Indication-

Originator Organization

Peking University Shenzhen Graduate School

Active Organization

Peking University Shenzhen Graduate School

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

AbstractCyclic GMP-AMP synthase (cGAS) is an essential sensor of aberrant cytosolic DNA for initiating innate immunity upon invading pathogens and cellular stress, which is considered as a potential drug target for autoimmune and autoinflammatory diseases. Here, we report the discovery of a class of cyclopeptide inhibitors of cGAS identified by an in vitro screening assay from a focused library of cyclic peptides. These cyclopeptides specifically bind to the DNA binding site of cGAS and block the binding of dsDNA with cGAS, subsequently inhibit dsDNA-induced liquid phase condensation and activation of cGAS. The specificity and potency of one optimal lead XQ2B were characterized in cellular assays. Concordantly, XQ2B inhibited herpes simplex virus-1 (HSV-1)-induced antiviral immune responses and enhanced HSV-1 infection in vitro and in vivo. Furthermore, XQ2B significantly suppressed the elevated levels of type I interferon and proinflammatory cytokines in primary macrophages from Trex1-/- mice and systemic inflammation in Trex1-/- mice. XQ2B represents the specific cGAS inhibitor targeting protein-DNA interaction and phase separation and serves as a scaffold for the development of therapies in the treatment of cGAS-dependent inflammatory diseases.

100 Deals associated with XQ2B

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