Delving into the Latest Updates on ZJU-37 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

Mechanism

RIPK1 inhibitors(Receptor-interacting serine/threonine-protein kinase 1 inhibitors), RIPK3 inhibitors(receptor interacting serine/threonine kinase 3 inhibitors)

Therapeutic Areas

Other Diseases

Active Indication

Inflammation

Inactive Indication-

Originator Organization

Xuzhou Medical University

Active Organization

Xuzhou Medical University

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC14H11ClFN3O3

InChIKeyJTQDNMQENCMSFD-SNVBAGLBSA-N

CAS Registry2408587-59-5

ObjectiveSystemic lupus erythematosus (SLE) is a type of autoimmune disease that involves multiple organs involved as well as cytokine dysregulation. The treatment of SLE is still challenging due to the side effects of the different drugs used. Receptor-interacting protein kinase 1 (RIPK1) is a kinase involved in T cell homeostasis and autoinflammation. Although clinical trials have shown that RIPK1 inhibition exhibits significant efficacy in different autoimmune diseases, its role in SLE remains unclear.MethodsMRL/lpr lupus-prone mice received RIPK1 inhibitor ZJU37 or vehicle intraperitoneally for 10 weeks. A BM12-induced chronic graft-versus-host-disease (cGVHD) lupus-like model was introduced in RIPK1 D138N mice or C57BL/6 mice. Nephritis, serum autoantibody levels, dysregulation of adaptive immune response and cytokines were compared in treated and untreated mice.ResultsZJU37 alleviated the clinical features of the MRL/lpr mice including nephritis and anti-dsDNA antibody production. In addition, ZJU37 treatment reduced the proportion of double-negative T cells in the spleen and the cytokines of TNFα, IFN-γ, IL-6, IL-17 and IL-1β in the serum. Moreover, RIPK1 D138N mice were able to prevent the cGVHD lupus-like model from SLE attack, manifesting as anti-dsDNA antibody production, the proliferation of germinal centre B cells, plasma cells, and T follicular helper cells as well as IgG and C3 deposits in kidneys.ConclusionRIPK1 inhibition has a protective effect in the mouse model of SLE and can potentially become a new therapeutic target for SLE in humans.

100 Deals associated with ZJU-37

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