Small molecules inhibit ex vivo tumor growth in bone

Donghui Zhou, Khuchtumur Bum-Erdene, David Xu, Degang Liu, Doug Tompkins, Rania S. Sulaiman, Timothy W. Corson, John M. Chirgwin, Samy O. Meroueh

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Bone is a common site of metastasis for breast, prostate, lung, kidney and other cancers. Bone metastases are incurable, and substantially reduce patient quality of life. To date, there exists no small-molecule therapeutic agent that can reduce tumor burden in bone. This is partly attributed to the lack of suitable in vitro assays that are good models of tumor growth in bone. Here, we take advantage of a novel ex vivo model of bone colonization to report a series of pyrrolopyrazolone small molecules that inhibit cancer cell invasion and ex vivo tumor growth in bone at single-digit micromolar concentration. We find that the compounds modulated the expression levels of genes associated with bone-forming osteoblasts, bone-destroying osteoclasts, cancer cell viability and metastasis. Our compounds provide chemical tools to uncover novel targets and pathways associated with bone metastasis, as well as for the development of compounds to prevent and reverse bone tumor growth in vivo.

Original languageEnglish (US)
Pages (from-to)6128-6134
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume26
Issue number23-24
DOIs
StatePublished - Dec 15 2018

ASJC Scopus subject areas

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

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