KU-177 is a Hsp90 ATPase homolog 1 (Aha1) inhibitor. By disrupting the interaction between Hsp90 and Aha1, it prevents the proliferation of primary MM and relapsed MM patient samples. It eliminates the proliferation and PI resistance induced by AHSA1 elevation.

Aha1/HSP90:4.08 μM

KU-177 (50 μM, 48 hours of action) was able to inhibit the proliferation of flow MRD-positive cells in samples from patients with primary and relapsed multiple myeloma (MM). [1]
In AHSA1 WT/OE cells, PSMD2 WT/OE cells and ANBL6 WT/DR cells, KU-177 (30 μM, treated for 48 hours) decreased proteasome activity. [1]
KU-177 disrupts the interaction of Aha1 with Hsp90 with an IC50 value of 4.08 μM without affecting the ATPase activity of Hsp90. [2]
KU-177 (25 μM, incubated at 37°C for 30 min) inhibits the aggregation of recombinant P301L tau protein but does not affect the refolding of fluorokinase by inhibiting Hsp90. [2]
KU-177 (10 μM, treated for 24 hours) exhibits the ability to disrupt the interaction of Aha1 with Hsp90 in SH-SY5Y neuroblastoma cells and SK-BR-3 breast cancer cells, while not significantly inhibiting the Hsp90 client protein Her2. [2]

In the 5TMM3VT multiple myeloma mouse model, KU-177 (1 mg/kg, intraperitoneal injection twice weekly for 4 weeks) was able to inhibit tumor growth and prolong survival without showing significant toxicity. When combined with Bortezomib (1 mg/kg, intraperitoneal injection), KU-177 demonstrated more significant therapeutic effects in vivo. [1]