OXC-201 is a first-in-class small molecule OGG1 inhibitor that has demonstrated proof of concept, and inhibition of pulmonary fibrosis in the bleomycin-induced disease model.  OGG1 has, besides its role in DNA repair, also a role in transcriptional regulation. OXC-201 halts the disease progress by inhibiting the expression of many fibrotic and inflammatory markers, resulting in tissue repair, inhibition of proliferation of fibroblasts and deposition of collagen in the alveolar wall. The DNA damage repair enzyme OGG1 is upregulated and recruited to DNA in conditions of oxidative stress such as pulmonary fibrosis where it repairs damaged nucleotides, such as 8-oxo guanine. OGG1 is a novel strategy for the treatment of IPF, blocking inflammatory and fibrotic cascades early in the process.

A novel inhibitor, OXC-201, was tested for its ability to attenuate inflammation and fibrosis in human IPF-PCLuS.  PCLuS was prepared from IPF human lung tissue collected at the time of lung transplantation. PCLuS were cultured in the presence of an OXC-201 at four escalating doses (2µM, 5µM, 10µM, 25µM) or Pirfenidone as a positive control.

The novel treatment, OXC-201, affected the secretion of fibrotic and inflammatory markers from IPF-PCLuS. OXC-201 demonstrated an ability to attenuate the secretion of fibrotic and inflammatory markers from IPF-PCLuS. We could see a downregulation of COL1A1, TIMP-1, fibronectin, TGF? and IL-8. The higher doses of OXC-201 reduced the secretion of fibrotic and inflammatory markers to the same or greater degree than that achieved following treatment with Pirfenidone. 

OXC-201 showed robust and dose-dependent anti-inflammatory and anti-fibrotic efficacy in IPF-PCLuS.