Heat Shock Proteins (Hsps) are a set of highly conserved molecular chaperone proteins that are activated in response to stresses that threaten a cell’s survival. Heat shock protein 90 (hsp90) is the best understood of the hsps and the most widely targeted for anticancer therapies. However, a hallmark of current clinical hsp90 inhibitors is that they induce a cell rescue mechanism, the heat shock response, which leads to eventual drug resistance. Here, we define the unique molecular profile of a compound that inhibits hsp90 function without inducing the heat shock response. Our small molecule uniquely modulates binding between hsp90 and the tetratricopeptide repeat containing immunophilins/ homologs, which leads to a decrease in hormone receptor protein levels. This work is proof of principle that controlling hormone receptor expression can occur via hsp90 inhibition without inducing pro-survival protein heat shock protein 70 (hsp70) or other proteins associated with the heat shock response. We show that blocking the activation of the heat shock response, in addition to inhibiting hsp90, is key to regulating hsp90’s oncogenic pathways.