747413-08-7

Basic information

• Product Name: VER-50589
• Synonyms: VER-50589;5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-Methoxyphenyl)isoxazole-3-carboxaMide;5-(5-Chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)-3-isoxazolecarboxamide
• CAS NO: 747413-08-7
• Molecular Formula: C19H17ClN2O5
• Molecular Weight: 388.80168
• EINECS: 604-604-1
• Product Categories: Inhibitors
• Mol File: 747413-08-7.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 583.0±50.0 °C(Predicted)
• Appearance: /
• Density: 1.360±0.06 g/cm3(Predicted)
• Solubility: ≥38.9 mg/mL in DMSO; insoluble in H2O; ≥57.2 mg/mL in EtOH
• PKA: 7.12±0.25(Predicted)
• CAS DataBase Reference: VER-50589(CAS DataBase Reference)
• NIST Chemistry Reference: VER-50589(747413-08-7)
• EPA Substance Registry System: VER-50589(747413-08-7)

Safety Data

• Hazardous Substances Data: 747413-08-7(Hazardous Substances Data)

Usage

Description

VER-50589 is a small molecule inhibitor that targets the intrinsic ATPase activity of recombinant yeast Hsp90, a molecular chaperone protein involved in the folding and stabilization of client proteins. It has been shown to exhibit antiproliferative activity in a panel of human cancer cell lines and nontumorigenic cells in vitro.

Uses

Used in Pharmaceutical Industry:
VER-50589 is used as an antiproliferative agent for its ability to inhibit the growth and proliferation of cancer cells. Its inhibitory effect on the intrinsic ATPase activity of yeast Hsp90 suggests its potential as a therapeutic agent for cancer treatment.
Used in Cancer Research:
VER-50589 is used as a research tool for studying the role of Hsp90 in cancer cell growth and proliferation. Its antiproliferative activity in various human cancer cell lines and nontumorigenic cells provides valuable insights into the molecular mechanisms underlying its anticancer effects and helps in the development of novel therapeutic strategies targeting Hsp90.

Biological Activity

ver-50589 is a potent inhibitor of hsp90 with ic50 value of 21 nm for hsp90β [1].heat shock protein 90 (hsp90) is a chaperone protein that stabilizes proteins against heat stress, assists proteins to fold properly and aids in protein degradation. also, hsp90 stabilizes proteins required for tumor growth.ver-50589 is a potent hsp90 inhibitor. ver-50589 inhibited recombinant yeast hsp90 atpase activity with ic50 value of 143 nm at 400 μm atp and inhibited recombinant human hsp90β with ic50 value of 821 nm in the presence of the activator aha1. also, ver-50589 bound to recombinant human hsp90β with kd value of 4.5 nm. in human cancer cells, ver-50589 exhibited antiproliferative activity with mean gi50 value of 78 nm. in ch1 human ovarian cells, ver-50589 inhibited cell growth with gi50 value of 32.7 nm. in ht29 cells, ver-50589 exhibited extensive glucuronidation and increased glucuronide levels by 50-fold, which were responsible for the resistance. in ch1doxr cells that were resistant to doxorubicin, ver-50589 exhibited similar cellular gi50 value compared with ch1 cells. in hct116 colon cancer cells, ver-50589 caused g1 and g2-m block. also, ver-50589 induced cytostasis and apoptosis [1].in athymic mice bearing ovcar3 human ovarian ascites tumors, ver-50589 completely inhibited hsp90. in mice bearing hct116 colon carcinoma xenografts, ver-50589 (100 mg/kg) reduced tumor volume by 30% and tumor weight by 26%. also, ver-50589 reduced expression of erbb2 and c-raf [1].

references

[1]. sharp sy, prodromou c, boxall k, et al. inhibition of the heat shock protein 90 molecular chaperone in vitro and in vivo by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues. mol cancer ther, 2007, 6(4): 1198-1211.

Relevant articles and documents

4,5-Diarylisoxazole Hsp90 chaperone inhibitors: Potential therapeutic agents for the treatment of cancer

Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as potential chemotherapeutic agents for cancer. Here, we describe the structure-based design, synthesis, structure - activity relationships and pharmacokinetics of potent small-molecule inhibitors of Hsp90 based on the 4,5-diarylisoxazole scaffold. Analogues from this series have high affinity for Hsp90, as measured in a fluorescence polarization (FP) competitive binding assay, and are active in cancer cell lines where they inhibit proliferation and exhibit a characteristic profile of depletion of oncogenic proteins and concomitant elevation of Hsp72. Compound 40f (VER-52296/NVP-AUY922) is potent in the Hsp90 FP binding assay (IC50 = 21 nM) and inhibits proliferation of various human cancer cell lines in vitro, with GI50 averaging 9 nM. Compound 40f is retained in tumors in vivo when administered i.p., as evaluated by cassette dosing in tumor-bearing mice. In a human colon cancer xenograft model, 40f inhibits tumor growth by ～50%.