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A potent and orally active antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in clinical development for cancer treatment

Journal of Medicinal Chemistry, ISSN: 0022-2623, Vol: 54, Issue: 8, Page: 2714-2726
2011
  • 235
    Citations
  • 0
    Usage
  • 125
    Captures
  • 1
    Mentions
  • 1
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    235
  • Captures
    125
  • Mentions
    1
    • News Mentions
      1
      • News
        1
  • Social Media
    1
    • Shares, Likes & Comments
      1
      • Facebook
        1

Most Recent News

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Article Description

We report the discovery and characterization of SM-406 (compound 2), a potent and orally bioavailable Smac mimetic and an antagonist of the inhibitor of apoptosis proteins (IAPs). This compound binds to XIAP, cIAP1, and cIAP2 proteins with K of 66.4, 1.9, and 5.1 nM, respectively. Compound 2 effectively antagonizes XIAP BIR3 protein in a cell-free functional assay, induces rapid degradation of cellular cIAP1 protein, and inhibits cancer cell growth in various human cancer cell lines. It has good oral bioavailability in mice, rats, non-human primates, and dogs, is highly effective in induction of apoptosis in xenograft tumors, and is capable of complete inhibition of tumor growth. Compound 2 is currently in phase I clinical trials for the treatment of human cancer. © 2011 American Chemical Society.

Bibliographic Details

Cai, Qian; Sun, Haiying; Peng, Yuefeng; Lu, Jianfeng; Nikolovska-Coleska, Zaneta; McEachern, Donna; Liu, Liu; Qiu, Su; Yang, Chao-Yie; Miller, Rebecca; Yi, Han; Zhang, Tao; Sun, Duxin; Kang, Sanmao; Guo, Ming; Leopold, Lance; Yang, Dajun; Wang, Shaomeng

American Chemical Society (ACS)

Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics

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