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Strategies to inhibit tumor associated integrin receptors: rationale for dual and multi-antagonists.
Progress toward development of antagonists targeting two or more members of the Arg-Gly-Asp (RGD) binding integrins, notably αv β3, αvβ5, α vβ6, αVβ8, α5β1, and αIIbβ3, as anticancer therapeutics are reviewed. Expand
Modification of the duocarmycin pharmacophore enables CYP1A1 targeting for biological activity.
Evidence is disclosed for the pathway of activation of a duocarmycin analogue, ICT2700, which targets CYP1A1 for biological activity and has the potential for tissue specific dose intensification as a means of significantly improving its therapeutic value. Expand
Colon Cancer–Specific Cytochrome P450 2W1 Converts Duocarmycin Analogues into Potent Tumor Cytotoxins
A novel approach for treatment of colon cancer that uses a locoregional activation of systemically inactive prodrug by the tumor-specific activator enzyme CYP2W1 is suggested. Expand
Chemical and biological explorations of the family of CC-1065 and the duocarmycin natural products.
The studies described herein form an excellent paradigm for the study and development of other natural products and the combination of synthesis with key biological experiments is a powerful tool to define the requirements for the development of natural products as potential therapeutic agents. Expand
Synthesis of the originally proposed structures of elatenyne and an enyne from Laurencia majuscula.
A bidirectional synthesis of the originally proposed structures for the natural products elatenyne and a chloroenyne from Laurencia majuscula is described along with a reassessment of the structuresExpand
Function and antagonism of beta3 integrins in the development of cancer therapy.
The role of the beta(3)-subfamily of integrins when expressed in normal and tumour tissue, the development of small-molecule antagonists ofbeta(3) integrin antagonists and their potential anti-cancer applications are summarized. Expand
Antitumor Activity of a Duocarmycin Analogue Rationalized to Be Metabolically Activated by Cytochrome P450 1A1 in Human Transitional Cell Carcinoma of the Bladder
The characterization of ICT2700, designed to be metabolized from a prodrug to a potent cytotoxin selectively by CYP1A1, supports the further development of I CT2700 as a tumor-selective treatment for human bladder cancers. Expand
RGD-Binding Integrins in Prostate Cancer: Expression Patterns and Therapeutic Prospects against Bone Metastasis
The multiple ways in which RGD-binding integrins contribute to prostate cancer progression and metastasis are highlighted, and the rationale for development of multi-integrin antagonists targeting theRGD- binding subfamily as molecularly targeted agents for its treatment is identified. Expand
Re-engineering of the duocarmycin structural architecture enables bioprecursor development targeting CYP1A1 and CYP2W1 for biological activity.
A library of duocarmycin bioprecursors based on the CPI and CBI scaffolds was synthesized and used to probe selective activation by cells expressing CYP1A1 and 2W1, CYPs known to be expressed in highExpand