Design, synthesis, and biological evaluation of bone-targeted proteasome inhibitors for multiple myeloma

Joseph K. Agyin, Bindu Santhamma, Sudipa S. Roy

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Multiple myeloma (MM) is an incurable neoplasm characterized by devastating and progressive bone destruction. Standard chemotherapeutic agents have not been effective at significantly prolonging the survival of MM patients and these agents are typically associated with often severe, dose-limiting side effects. There is great need for methods to target the delivery of novel, effective cytotoxic agents specifically to bone, where myeloma cells reside. We have synthesized and evaluated the effects of the bone-targeted proteasome inhibitors PS-341-BP-1, PS-341-BP-2 and MG-262-BP on cell proliferation using the mouse 5TGM1 and human RPMI 8226 cell lines in vitro. The compounds exhibit strong cytotoxicity on MM cell lines and reduce the number of viable cells in a dose dependent manner.

Original languageEnglish (US)
Pages (from-to)6455-6458
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number23
DOIs
StatePublished - Dec 1 2013

Keywords

  • Bisphosphonate conjugate
  • Bone-targeted
  • Boronic acid
  • Multiple myeloma
  • Proteasome inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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