Chemokine receptor CCR10
The chemokine receptor CCR10 has been implicated in inflammatory diseases and tumors of epithelia (in skin, respiratory and gastrointestinal tract). The ligand CCL27 (CTACK) is secreted by keratinocytes in the skin and attracts CCR10 expressing cells like T-cells to the skin. Another ligand of this receptor is CCL28 (MEC) which is expressed in epithelial cells of the respiratory and gastrointestinal tract. If over-expressed in certain diseases it also attracts respective T-cells.
A follow-up on hits from screening of the PEMfinder® library for CCR10 antagonists resulted in the identification of a first lead compound POL7085.
With POL7085, Polyphor could demonstrate for the first the time efficacy of a CCR10 antagonist in models of melanoma metastasis and respiratory diseases like asthma.
Prompted by these encouraging results obtained by systemic administration or direct application to the lung, Polyphor initiated an optimization program which yielded two CCR10 antagonists with improved pharmacological and pharmacokinetic properties suitable for in-depth characterization and subsequent preclinical development in different therapeutic areas.