Novel Estrogen Receptor: ER-α36

Dr. Charlie Wang has recently discovered and characterized a novel variant of ER receptor, ER-α36, which mediates membrane-initiated estrogen signaling and estrogen-stimulated cell proliferation. ER-α36 has considerable sequence homology with previously identified ER-α66, but distinguishes from the previous one by a unique C-terminal 27 amino acid sequence and appear to function through a totally different mechanism.

Computer modeling of the new receptor structure reveals that ER-α36 protein is structurally "unhindered" by the lacking of a stretch of helical chain present in ER-α66, resulting in a more "open" ligand-binding pocket in ER-α36.  By leveraging clues from the formulations of traditional Chinese medicine and our proprietary bio-assay screening system, we had initially identified a number of naturally derived bioactive small molecules that specifically inhibit ER-α36 function. With increasing understanding of the structure-activity relationship of various molecules, we have modified our lead molecules and generated a number of NCE pipeline molecules targeting the novel ER-α36 receptor.