2. Academic Validation
  3. The pyrido[b]indole MDM2 inhibitor SP-141 exerts potent therapeutic effects in breast cancer models

The pyrido[b]indole MDM2 inhibitor SP-141 exerts potent therapeutic effects in breast cancer models

  • Nat Commun. 2014 Oct 1;5:5086. doi: 10.1038/ncomms6086.
Wei Wang 1,  Jiang-Jiang Qin 2,  Sukesh Voruganti 2,  Kalkunte S Srivenugopal 3,  Subhasree Nag 2,  Shivaputra Patil 4,  Horrick Sharma 4,  Ming-Hai Wang 3,  Hui Wang 5,  John K Buolamwini 4,  Ruiwen Zhang 1
Affiliations

Affiliations

  • 1 1] Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas 79106, USA [2] Cancer Biology Center, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas 79106, USA.
  • 2 Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas 79106, USA.
  • 3 1] Cancer Biology Center, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas 79106, USA [2] Department of Biomedical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas 79106, USA.
  • 4 Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
  • 5 Key Laboratory of Food Safety Research Center, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
PMID: 25271708 DOI: 10.1038/ncomms6086
Abstract

A requirement for Mouse Double Minute 2 (MDM2) oncogene activation has been suggested to be associated with Cancer progression and metastasis, including breast Cancer. To date, most MDM2 inhibitors have been designed to block the MDM2-p53-binding interphase, and have low or no efficacy against advanced breast Cancer with mutant or deficient p53. Here we use a high-throughput screening and computer-aided, structure-based rational drug design, and identify a lead compound, SP-141, which can directly bind to MDM2, inhibit MDM2 expression and induce its autoubiquitination and proteasomal degradation. SP-141 has strong in vitro and in vivo antibreast Cancer activity, with no apparent host toxicity. While further investigation is needed, our data indicate that SP-141 is a novel targeted therapeutic agent that may especially benefit patients with advanced disease.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-110182
    99.94%, MDM2 Inhibitor