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

Bioorg Med Chem Lett. 2013 Dec 1;23(23):6455-8. doi: 10.1016/j.bmcl.2013.09.043. Epub 2013 Sep 21.


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.

Keywords: Bisphosphonate conjugate; Bone-targeted; Boronic acid; Multiple myeloma; Proteasome inhibitor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Bone Density Conservation Agents / chemical synthesis
  • Bone Density Conservation Agents / chemistry
  • Bone Density Conservation Agents / pharmacology
  • Bone and Bones / drug effects
  • Bone and Bones / pathology
  • Boronic Acids / chemical synthesis
  • Boronic Acids / chemistry
  • Boronic Acids / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Diphosphonates / chemical synthesis
  • Diphosphonates / chemistry
  • Diphosphonates / pharmacology
  • Humans
  • Mice
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy*
  • Proteasome Inhibitors / chemical synthesis
  • Proteasome Inhibitors / chemistry*
  • Proteasome Inhibitors / pharmacology*


  • Antineoplastic Agents
  • Bone Density Conservation Agents
  • Boronic Acids
  • Diphosphonates
  • Proteasome Inhibitors