|Publication Type||Journal Article|
|Year of Publication||2009|
|Authors||Stanton, BZ, Peng, LF, Maloof, N, Nakai, K, Wang, X, Duffner, JL, Taveras, KM, Hyman, JM, Lee, SW, Koehler, AN, Chen, JK, Fox, JL, Mandinova, A, Schreiber, SL|
|Journal||Nature chemical biology|
Small-molecule inhibition of extracellular proteins that activate membrane receptors has proven to be extremely challenging. Diversity-oriented synthesis and small-molecule microarrays enabled the discovery of robotnikinin, a small molecule that binds the extracellular Sonic hedgehog (Shh) protein and blocks Shh signaling in cell lines, human primary keratinocytes and a synthetic model of human skin. Shh pathway activity is rescued by small-molecule agonists of Smoothened, which functions immediately downstream of the Shh receptor Patched.