Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, ultimately fatal lung disease with high morbidity. IPF is characterized by thick collagen scar tissue and expansion of collagen synthesising cells in the lung which results in severe restriction of lung capacity and function. IPF is classified as a rare disease affecting between 200,000 and 300,000 in the Western world. In the UK it is estimated there are around 30,000 cases with limited treatment options. Given ageing and Covid infection is a risk factor of IPF, a significant increase in IPF cases has been predicted. Current treatments are limited by their side effects, their inability to change the overall progression of the disease and high mortality within 3 to 5 years after diagnosis. IPF remains a very substantial unmet medical need. It has been shown that the pro-fibrotic enzyme Transglutaminase 2 (TG2) plays a key role in IPF progression. TG2 acts by crosslinking matrix proteins like a glue. It also activates key fibrotic growth factors leading to the activation of fibrosis causing cells. This crosslinked fibrous tissue is highly resistant to remodelling and normal tissue repair is compromised, which can lead to organ failure. Our innovative work has demonstrated the potential of TG2 small molecule inhibitors as an effective treatment of IPF in both cell and animal models. Through a £2.1million MRC DPFS research programme, we have developed a new series of TG2 inhibitors with good druggable properties and significant potential for development into an oral treatment for fibrotic disease. This would offer an effective treatment to sufferers of IPF. In this project, based on our existing comprehensive properties of our candidate inhibitors, we have selected one of our lead candidates with the aim of advancing our knowledge of this candidate via generating further preclinical data which will validate this compound as a candidate to attract further substantial investment funding allowing us to take it to the clinic.