Delving into the Latest Updates on SAR-20347 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

JAK1 x TYK2

Mechanism

JAK1 inhibitors(Tyrosine-protein kinase JAK1 inhibitors), TYK2 inhibitors(Tyrosine-protein kinase 2 inhibitors)

Therapeutic Areas

Immune System DiseasesSkin and Musculoskeletal Diseases

Active Indication-

Inactive Indication

Psoriasis

Originator Organization

Sareum Holdings Plc

Active Organization-

Inactive Organization

Sareum Holdings Plc

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC21H18ClFN4O4

InChIKeyHEDPDFHTQKEORT-UHFFFAOYSA-N

CAS Registry1450881-55-6

AbstractPsoriasis is a chronic autoimmune disease affecting the skin and characterized by aberrant keratinocyte proliferation and function. Immune cells infiltrate the skin and release proinflammatory cytokines that play important roles in psoriasis. The Th17 network, including IL-23 and IL-22, has recently emerged as a critical component in the pathogenesis of psoriasis. IL-22 and IL-23 signaling is dependent on the JAK family of protein tyrosine kinases, making JAK inhibition an appealing strategy for the treatment of psoriasis. In this study, we report the activity of SAR-20347, a small molecule inhibitor with specificity for JAK1 and tyrosine kinase 2 (TYK2) over other JAK family members. In cellular assays, SAR-20347 dose dependently (1 nM–10 μM) inhibited JAK1- and/or TYK2-dependent signaling from the IL-12/IL-23, IL-22, and IFN-α receptors. In vivo, TYK2 mutant mice or treatment of wild-type mice with SAR-20347 significantly reduced IL-12–induced IFN-γ production and IL-22–dependent serum amyloid A to similar extents, indicating that, in these models, SAR-20347 is probably acting through inhibition of TYK2. In an imiquimod-induced psoriasis model, the administration of SAR-20347 led to a striking decrease in disease pathology, including reduced activation of keratinocytes and proinflammatory cytokine levels compared with both TYK2 mutant mice and wild-type controls. Taken together, these data indicate that targeting both JAK1- and TYK2-mediated cytokine signaling is more effective than TYK2 inhibition alone in reducing psoriasis pathogenesis.

100 Deals associated with SAR-20347

Login to view more data