Degrasyn-like symmetrical compounds: possible therapeutic agents for multiple myeloma (MM-I).

Abstract

A series of degrasyn-like symmetrical compounds have been designed, synthesized, and screened against B cell malignancy (multiple myeloma, mantle cell lymphoma) cell lines. The lead compounds T5165804 and CP2005 showed higher nanomolar potency against these tumor cells in comparison to degrasyn and inhibited Usp9x activity in vitro and in intact cells. These observations suggest that this new class of compounds holds promise as cancer therapeutic agents.

• Authors: Zhenghong Peng, David S Maxwell, Duoli Sun, Basvoju A Bhanu Prasad, Paul T Schuber Jr, Ashutosh Pal, Yunming Ying, Dongmei Han, Liwei Gao, Shimei Wang, Alexander Levitzki, Vaibhav Kapuria, Moshe Talpaz, Matthew Young, Hollis D Showalter, Nicholas J Donato, William G Bornmann
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 22 Issue 4 Pg. 1450-8 (Feb 15 2014) ISSN: 1464-3391 [Electronic] England
• PMID: 24457091 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014. Published by Elsevier Ltd.

Chemical References

• Antineoplastic Agents
• Cyanoacrylates
• Nitriles
• Pyridines
• USP9X protein, human
• degrasyn
• Ubiquitin Thiolesterase

Topics

• Antineoplastic Agents (chemistry, therapeutic use, toxicity)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cyanoacrylates
• Dimerization
• Humans
• Models, Molecular
• Multiple Myeloma (drug therapy)
• Nitriles (chemistry, pharmacology, therapeutic use)
• Pyridines (chemistry, pharmacology, therapeutic use)
• Ubiquitin Thiolesterase (antagonists & inhibitors, metabolism)