VER-155008

• CAT Number: I000503
• CAS Number: 1134156-31-2
• Molecular Formula: C25H23Cl2N7O4
• Molecular Weight: 556.4
• Purity: ≥95%
• Synonyms: 4-[[(2R,3S,4R,5R)-5-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxymethyl]benzonitrile
• Target: HSP
• Solubility: DMSO: ≥ 37 mg/mL
• Storage: Store at -20°C
• IC50: 5.3-14.4 uM(GI50); 80 nM(Kd)
• InChIKey: ZXGGCBQORXDVTE-UMCMBGNQSA-N
• SMILES: O[C@H]1[C@@H](O)[C@H](N2C(NCC3=CC=C(Cl)C(Cl)=C3)=NC4=C2N=CN=C4N)O[C@@H]1COCC5=CC=C(C#N)C=C5

VER-155008 (CAT: I0005032) is a potent and selective inhibitor of the heat shock protein 70 (Hsp70) family of proteins. It acts by binding to the ATPase domain of Hsp70, preventing its ATPase activity and disrupting its chaperone function. Hsp70 is involved in protein folding, stability, and degradation, and plays a crucial role in cellular stress response. By inhibiting Hsp70, VER-155008 can impact various cellular processes and pathways, making it a valuable tool in research and potentially offering therapeutic applications in diseases where Hsp70 is dysregulated, such as cancer and neurodegenerative disorders.

Reference

1. Exp Biol Med (Maywood). 2014 May;239(5):638-45. doi: 10.1177/1535370214527899.
Epub 2014 Mar 27.
VER-155008, a small molecule inhibitor of HSP70 with potent anti-cancer activity
on lung cancer cell lines.
Wen W(1), Liu W, Shao Y, Chen L.
Author information:
(1)Department of Thoracic Surgery, People/’s Hospital of Jiangsu Province, Nanjing
Medical University, Nanjing 210029, China.
Lung cancer is the most common malignancy and exhibits significant morbidity and
mortality worldwide. Among all lung cancer subtypes, non-small-cell lung cancer
(NSCLC) accounts for the majority of all lung cancer cases. Although there have
been intensive investigations on the underlying mechanism of NSCLC development
and progression, the exact molecular basis is not well understood. Further
insights on important molecular regulators of lung cancer are needed for
development of novel therapeutics. The heat shock protein (HSP) family is a group
of molecular chaperones that assist in protein folding, modification, and
transportation. Different HSPs are essential for tumor cell survival by binding
diverse client proteins and regulating homeostasis. In the current study, we
sought to characterize HSP70 and HSP90 as potent regulators of NSCLC growth. Our
results indicate that differential expression of HSP70 is associated with the
malignant phenotype of NSCLC cell lines and plays an important regulatory role in
NSCLC cell proliferation. Moreover, a specific inhibitor of HSP70, VER-155008
significantly inhibits NSCLC proliferation and cell cycle progression. We showed
that this effect is largely abolished by HSP70 overexpression, indicating that
the inhibitory effect of VER-155008 on cell growth is specifically through HSP70
inhibition. In addition, 17-AAD, an inhibitor of HSP90, exerts a potent
synergistic effect on NSCLC proliferation with VER-155008. We also observed that
inhibition of HSP70 by VER-155008 can sensitize A549 cells to ionizing radiation.
These data provide proof-of-principle that VER-155008 can be a good candidate for
NSCLC treatment and HSP machinery is a good target for developing NSCLC
therapeutics.