Retaspimycin Hydrochloride is a potent and water-soluble Hsp90 inhibitor(Hsp90 and Grp9 with EC50s of 119 nM).

HSP90:119 nM （EC50）, Grp94:119 nM （EC50）

Retaspimycin is an inhibitor of Hsp90. Retaspimycin can abrogate both the unfolded protein response element (UPRE) and ERSE-driven luciferase activity in non-treated U266 and MM.1s cells as well as in Tunicamycin (Tm)-treated cells. Incubation of Retaspimycin potently suppresses both Akt and MAPKs phosphorylation in both sensitive and Trastuzumab-resistant cells. Total levels of Akt decreased in all 4 cell lines (BT474, SKBR-3, HCC1569, and HCC1569) in a dose-dependent manner. However, levels of total MAPKs are not significantly altered with Retaspimycin treatment[2].

Tumor regression of Trastuzumab-sensitive BT474 cell-derived xenografts independently induceed by Retaspimycin and Trastuzumab. Xenografts derived from BT474R cells continue to grow in the presence of Trastuzumab but are still sensitive to Retaspimycin. When used in combination, Retaspimycin and Trastuzumab add only marginal benefits to Retaspimycin monotherapy. Retaspimycin as a single agent is more efficacious than Trastuzumab in inhibiting tumor growth in HCC1569 xenografts[2].