Zelavespib (hydrochloride)

Zelavespib (PU-H71) hydrochloride is a potent Hsp90 inhibitor, with an IC₅₀ of 51 nM in MDA-MB-468 cells. IC50 & Target:IC50: 51 nM (Hsp90, in MDA-MB-468 cells)^[1] In Vitro: Zelavespib hydrochloride is a potent Hsp90 inhibitor, with an IC₅₀ of 51 nM in MDA-MB-468 cells. Zelavespib inhibits the growth of several tumor cells, such as MDA-MB-468, MDA-MB-231 and HCC-1806 cells, with IC₅₀s of 65 ± 8 nM, 140 ± 5 nM and 87 ± 3 nM, respectively, and such inhibition is associated with a G2-M block arrest. Zelavespib (10-1000 nM) induces significant apoptosis in triple-negative breast cancers (TNBCs). Zelavespib (0.5, 1 μM) also downregulates oncoproteins involved in the invasive potential of TNBCs^[1]. Zelavespib (0.5 μM) decreases and depletes the BCR signaling kinases. Zelavespib (0.25-10 μM) is cytotoxic to CLL cells but shows minimal effects on PBMC or resting B cells. In addition, Zelavespib (0-1 μM) reduces CLL viability via the induction of mitochondrial apoptosis, and antagonizes the survival signals from CLL microenvironment at 0.5 μM^[2]. Zelavespib (0.05 μM) induces apoptosis of MDA-MB-231, BT-474, and MCF7 cells, and such induction is enhanced by TNF-α. Zelavespib (0.05 μM) degradates IKKβ, and down-regulates the NF-κB transcriptional activity induced by TNF-α treatment^[3]. In Vivo: Zelavespib hydrochloride (75 mg/kg, i.p.) causes intratumor accumulation, extends down-regulation of anti-tumor driving molecules, completes and retains responses at nontoxic doses in MDA-MB-468 tumor-bearing mice. Zelavespib (75 mg/kg 3×week, i.p.) suppresses the gowth of tumors, and such an effect is associated with down-regulation of several Hsp90-regulated malignancy driving proteins^[1].