Zelavespib hydrochloride

• CAT Number: I046414
• CAS Number: 2095432-24-7
• Molecular Formula: C18H22ClIN6O2S
• Molecular Weight: 548.83
• Purity: ≥95%
• Synonyms: 8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine;hydrochloride
• InChI: InChI=1S/C18H21IN6O2S.ClH/c1-10(2)21-4-3-5-25-17-15(16(20)22-8-23-17)24-18(25)28-14-7-13-12(6-11(14)19)26-9-27-13;/h6-8,10,21H,3-5,9H2,1-2H3,(H2,20,22,23);1H
• InChIKey: HUAKDRZHOBLKGD-UHFFFAOYSA-N
• SMILES: CC(C)NCCCN1C2=NC=NC(=C2N=C1SC3=C(C=C4C(=C3)OCO4)I)N.Cl

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

Reference

[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.
 [Content Brief]

[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.
 [Content Brief]

[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.
 [Content Brief]