2. Academic Validation
  3. Development of a novel near-infrared fluorescent theranostic combretastain A-4 analogue, YK-5-252, to target triple negative breast cancer

Development of a novel near-infrared fluorescent theranostic combretastain A-4 analogue, YK-5-252, to target triple negative breast cancer

  • Bioorg Med Chem. 2017 Apr 1;25(7):2226-2233. doi: 10.1016/j.bmc.2017.02.046.
Yali Kong 1,  Jacqueline Smith 2,  Kongwen Li 3,  Jake Cui 4,  John Han 5,  Shujie Hou 6,  Milton L Brown 7
Affiliations

Affiliations

  • 1 Drug Discovery & Development, Inova Schar Cancer Institute; Drug Discovery Center, Inova Center for Personalized Health, 3225 Gallows Rd, Fairfax, VA 22031, United States.
  • 2 Department of Natural Sciences, Bowie State University, 14000 Jericho Park Dr, Crawford 207A, Bowie, MD 20716, United States.
  • 3 Fairfax High School, 3501 Rebel Run, Fairfax, VA 22030, United States.
  • 4 Thomas Jefferson High School for Science and Technology, 6560 Braddock Road, Alexandria 22312, United States.
  • 5 James Madison High School, 2500 James Madison Drive, Vienna, VA 22181, United States.
  • 6 Department of Oncology, Center for Drug Discovery, Georgetown University Medical Center, 3970 Reservoir Rd, Washington D.C. 20057, United States.
  • 7 Drug Discovery & Development, Inova Schar Cancer Institute; Drug Discovery Center, Inova Center for Personalized Health, 3225 Gallows Rd, Fairfax, VA 22031, United States. Electronic address: Milton.Brown@inova.org.
PMID: 28284864 DOI: 10.1016/j.bmc.2017.02.046
Abstract

The treatment of triple negative breast Cancer (TNBC) is a significant challenge to Cancer research. The lack of hormone receptors limits the treatment options available to patients with this diagnosis, forcing them to endure prolonged radiation and chemotherapy. Anti-angiogenesis is a chemotherapeutic strategy that targets the vasculature of tumors. Combretastatin A-4 (CA-4) is a well-known vasculature-disrupting agent, which has been shown to effectively kill a variety of cancers through inhibition of tubulin polymerization. Due to its toxicity, small molecule analogues of CA-4 have been sought out. We have designed a novel dual action CA-4 prodrug, YK-5-252, which releases the drug through a disulfide bond cleavage mechanism and contains a near-infrared (NIR) fluorophore, which allows fluorescence monitoring of cleavage. This disulfide linkage causes CA-4 to become effective only when released by glutathione (GSH) reducing the toxicity of the drug while simultaneously releasing the NIR fluorophore. Therefore the prodrug, YK-5-252, represents a novel CA-4 analogue which has reduced toxicity and can be used for theranostics imaging.

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