PEGylation enhances the tumor selectivity of melanoma-targeted conjugates.

In the development of our melanoma-selective delivery approach, three preselected conjugates of 5-iodo-2'-deoxyuridine (IUdR) to the ICF01012 melanoma-carrier were radiolabelled with iodine-125, and their in vivo distribution profile was determined. A radioiodination method for the conjugate 1a and its PEGylated derivatives 1b-c was developed via electrophilic iododestannylation in good radiochemical yield with excellent radiochemical purity (>99%). When administered to melanoma-bearing mice, the PEGylated conjugates exhibited an increased tumour uptake with a prolonged residence time.

HER2 overexpression a major risk factor for recurrence in pT1a-bN0M0 breast cancer: results from a French regional cohort.

The management of pT1a-bN0M0 breast cancer remains an area of controversy. Data from 714 patients classified as having pT1a-bN0M0 breast cancer and treated, from 1999 to 2004 in the Languedoc-Roussillon France, were analyzed. The human epidermal growth factor receptor 2 (HER2) status analyses were centralized.

Spacer optimization of new conjugates for a melanoma-selective delivery approach.

In the search for more selective anticancer drugs, we designed and synthesized seven conjugates varying the structure of the linker connecting the 5-iodo-2'-deoxyuridine (IUdR) to the ICF 01012 melanoma-carrier for potential intratumoural specific drug release. Chemical and in vitro metabolic stability evaluations showed that, except for the ester conjugate (1), the ketal (2b), acetal (2a), carbonate (4) and carbamate (3) conjugates were compatible with our approach. The acetal (2a) and its PEGylated derivative (2c) were of particular interest for further in vivo development owing to their respective pH-dependent stability and limited metabolic degradation in order to exploit the acidic subcellular environment of malignant melanocytes to trigger the release of therapeutics upon internalization in cells.

Heck, direct arylation, and hydrogenation: two or three sequential reactions from a single catalyst.

Palladium-catalyzed tandem multifunctional reactions leading to the synthesis of substituted biaryl molecules have been developed including tandem Heck-direct arylation and tandem-sequential Heck-direct arylation-hydrogenation. These reactions occur in good yield and have been employed in the synthesis of a cytotoxic biaryl compound.