Orphan Nuclear Receptors
NRT1 an ‘adopted’ nuclear receptor, is expressed in tissues derived from endodermal origins including: liver, intestine, exocrine pancreas, ovary, pre-adipocyte, and placenta.
NRT1 modulates diverse physiological functions including: bile acid metabolism, and glucose homeostasis, and is involved in cell cycle regulation, through Wnt/β-catenin signalling.
Aberrant expression and activity of NRT1 has been linked to a range of pathological conditions, hence both positive or negative modulators of NRT1, would be therapeutic benefit. TES Pharma is progressing a number of small molecule modulators of NRT1 towards animal model studies.
NRT2 is an orphan nuclear receptor and an essential gatekeeper of T cell effector (CD4+ and CD8+) functions. NRT2 is also an essential signalling node governing the complex host-tumour interactions at the crossroads between inflammation and cancer and is highly expressed in various types of cancer including; breast cancer, lymphomas and colorectal tumours.
Since cancer cells with lower levels of NRT2 have enhanced sensitivity to anticancer drugs, modulators of NRT2 have great potential as small molecule checkpoint inhibitors in immuno-oncology. TES Pharma is progressing a number of templates through hit expansion.