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

  title={Development of a novel near-infrared fluorescent theranostic combretastain A-4 analogue, YK-5-252, to target triple negative breast cancer.},
  author={Yali Kong and Jacqueline Smith and Kongwen Li and Jake Cui and John Song Mou Han and Shujie Hou and Milton L. Brown},
  journal={Bioorganic \& medicinal chemistry},
  volume={25 7},
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… 
9 Citations
Fluorogenic reaction-based prodrug conjugates as targeted cancer theranostics.
The work summarized in this Tutorial Review will help define the role fluorogenic reaction-based, cancer-targeting theranostics may have in advancing drug discovery efforts, as well as improving the understanding of cellular uptake and drug release mechanisms.
NQO1-selective activated prodrugs of combretastatin A-4: Synthesis and biological evaluation.
NQO1 can be used as a specific delivery system for releasing antic cancer agents and prodrug 4 can serve as a candidate lead for developing specific anticancer agents.
Recent advances in combretastatin based derivatives and prodrugs as antimitotic agents.
The present review highlights the investigations into the parallel development of both new CA-4 based derivatives and prodrugs in the past few years.
Recent advances in construction of small molecule-based fluorophore-drug conjugates
This short review of recent developments of small molecule-based fluorophore-drug conjugates, including non-cleavable and cleavable ones, that are capable of visualizing drug delivery are discussed.
Quest for novel fluorogenic xanthene dyes: Synthesis, spectral properties and stability of 3-imino-3H-xanthen-6-amine (pyronin) and its silicon analog
Abstract To expand the range of primary aniline fluorophores available and suitable for the design of fluorogenic protease probes, the synthesis of 3-imino-3 H -xanthen-6-amine (known as pyronin) and
Synthesis and bioevaluation of N-(3,4,5-trimethoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-amines as tubulin polymerization inhibitors with anti-angiogenic effects.
Compound 15c showed strong anti-tubulin polymerization activity, changed the morphology of tubulin, and arrested the cell cycle at the G2/M transition in MCF-7 cells, highlighting that compound 15c is a potential antitumor compound that are worthy of further development.
On-Water Cp*Ir(III)-Catalyzed C-H Functionalization for the Synthesis of Chromones through Annulation of Salicylaldehydes with Diazo-Ketones.
A high-valent Ir(III)-catalyzed C-H bond functionalization is carried out for the first time on water for the synthesis of a biologically relevant chromone moiety in a one-pot decarboxylation by employing tert-butyl diazoester.
Molecular Theranostics for Cancer Therapy


Structure-based discovery of a boronic acid bioisostere of combretastatin A-4.
It is demonstrated that the cis-6 boronic acid bioisostere of CA-4 inhibits tubulin assembly, competitively displaces colchicine, and is a low-nanomolar inhibitor of human cancer cell lines.
In vivo and in situ tracking cancer chemotherapy by highly photostable NIR fluorescent theranostic prodrug.
The tumor-targeting ability and the specific drug release in tumors make DCM-S-CPT as a promising prodrug, providing significant advances toward deeper understanding and exploration of theranostic drug-delivery systems.
A review and update of the current status of the vasculature-disabling agent combretastatin-A4 phosphate (CA4P)
The potential of combining VDAs with antiangiogenic therapies has shown considerable promise in preclinical models and such combinations are now beginning to be evaluated in patients.
Combretastatin A4 phosphate: background and current clinical status
Combretastatin A4 phosphate is a water-soluble prodrug of the cis-stilbene CA4 originally isolated from the tree Combretum caffrum that induces blood flow reductions and subsequent tumour cell death in a variety of preclinical models.
Medicinal chemistry of combretastatin A4: present and future directions.
The present review will concentrate primarily on the medicinal chemistry of one of these drugs, combretastatin A4 (CA-4 a), which has been brought forward into the drug pipeline that share this mechanism of action.
A boronic acid chalcone analog of combretastatin A-4 as a potent anti-proliferation agent.
This study identified a boronic acid chalcone with inhibition towards 16 human cancer cell lines in the 10-200nM range, and another three cell lines with GI(50)-values below 10nM, which has significant anti-angiogenesis effects demonstrated by HUVEC tube formation and aortic ring assay.
A Phase I Trial of Radioimmunotherapy with 131I-A5B7 Anti-CEA Antibody in Combination with Combretastatin-A4-Phosphate in Advanced Gastrointestinal Carcinomas
This is believed to be the first trial reporting the combination of radioimmunotherapy and vascular disruptive agent; each component was shown to function, and myelosuppression was dose-limiting.
Phase I Trial of Combretastatin A4 Phosphate (CA4P) in Combination with Bevacizumab in Patients with Advanced Cancer
CA4P in combination with bevacizumab appears safe and well tolerated in this dosing schedule, and DCE-MRI showed statistically significant reductions in tumor perfusion/vascular permeability, which reversed after CA4P alone but which were sustained following bevacsumab.
Evaluation of the vascular targeting agent combretastatin a-4 prodrug on retinal neovascularization in the galactose-fed dog.
The failure of CA-4P to ameliorate neovascularization suggests that chronic, long-term administration may be required to destroy the slowly growing retinal endothelial cells.
Antineoplastic agents. 487. Synthesis and biological evaluation of the antineoplastic agent 3,4-methylenedioxy-5,4'-dimethoxy-3'-amino-Z-stilbene and derived amino acid amides.
Most of the amides caused a marked increase in the mitotic index of treated cells, indicating that tubulin was their intracellular target.