PU-H71 hydrochloride

PU-H71 hydrochloride is a potent Hsp90 inhibitor, with an IC50 of 51 nM in MDA-MB-468 cells. HSP90|51 nM (IC50, MDA-MB-468 cells)

PU-H71 hydrochloride is a potent Hsp90 inhibitor, with an IC50 of 51 nM in MDA-MB-468 cells. PU-H71 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. PU-H71 (10-1000 nM) induces significant apoptosis in triple-negative breast cancers (TNBCs). PU-H71 (0.5, 1 μM) also downregulates oncoproteins involved in the invasive potential of TNBCs[1]. PU-H71 (0.5 μM) decreases and depletes the BCR signaling kinases. PU-H71 (0.25-10 μM) is cytotoxic to CLL cells but shows minimal effects on PBMC or resting B cells. In addition, PU-H71 (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]. PU-H71 (0.05 μM) induces apoptosis of MDA-MB-231, BT-474, and MCF7 cells, and such induction is enhanced by TNF-α. PU-H71 (0.05 μM) degradates IKKβ, and down-regulates the NF-κB transcriptional activity induced by TNF-α treatment[3].

PU-H71 (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. PU-H71 (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].

[1]. Caldas-Lopes E, et al. Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Proc Natl Acad Sci U S A. 2009 May 19;106(20):8368-73. [2]. Guo A, et al. HSP90 stabilizes B-cell receptor kinases in a multi-client interactome: PU-H71 induces CLL apoptosis in a cytoprotective microenvironment. Oncogene. 2017 Jun 15;36(24):3441-3449. [3]. Qu Z, et al. PU-H71 effectively induces degradation of IκB kinase β in the presence of TNF-α. Mol Cell Biochem. 2014 Jan;386(1-2):135-42.