top of page

RUNAWAY

IMMUNE RESPONSE

Chronically inflamed tissue is a consequence of a runaway immune response that is characterized by the deposition of connective tissue enriched with collagen and fibronectin.This is fibrosis, a phenomenon that inexorably leads to permanent scarring of the tissue, organ malfunction and ultimately death due to organ failure. Fibrosis is also a major pathological feature of many chronic autoimmune diseases, including rheumatoid arthritis, ulcerative colitis and lupus. 

 

Though it affects nearly every tissue in the body, the exact nature and sequence of events that lead to fibrosis is unknown though the infiltration of mononuclear immune cells is a common feature.  This infiltration is the basis for the essential process of wound-healing that is triggered in damaged tissues, but dysregulation of the healing process leads to excessive deposits of connective tissue. 

 

The continuous debris from damaged cells leads to the  chronic activation of STING (Stimulator of Interferon Genes) an important transducer of innate immune signaling.    The pathology associated with constitutively activated STING is most evident in the spectrum of human autoimmune disorders termed SAVI (STING-associated vasculopathy with onset in infancy) that can be a terminal disease striking young children.

STING antagonist

Curadev initiated a small molecule STING antagonist program that has yielded novel chemotypes that inactivate STING.  The program is developing distinct pharmacophores with potentially distinct mechanism of STING inactivation. 

TNIK

Curadev has nominated COMPOUND 6, its lead small-molecule TNIK inhibitor, as a candidate for US FDA IND. The TNIK inhibitor program has yielded potent and selective TNIK inhibitors that alleviate liver fibrosis in murine models. COMPOUND 6 is also in preclinical development for metabolic disorders.

CLK/DYRK DUAL INHIBITOR PROGRAM

Curadev has nominated COMPOUND 9, its lead small-molecule dual CLK/DYRK inhibitor, as a candidate for US FDA IND filing. The dual CLK/DYRK inhibitor COMPOUND 9, a potent and selective dual inhibitor is being developed for the treatment of osteoarthritis by intra-articular (IA) injection.

bottom of page