Design, synthesis and biological evaluation of phenol-linked uncialamycin antibody-drug conjugates.

Uncialamycin is one of the structurally simpler and newer members of enediyne family of natural products. It exhibits highly potent activity against several types of bacteria and cancer cells. Described herein is a strategy for the targeted delivery of this cytotoxic agent to tumors using an antibody-drug conjugate (ADC) approach.

Fucosyl monosialoganglioside: Quantitative analysis of specific potential biomarkers of lung cancer in biological matrices using immunocapture extraction/tandem mass spectrometry.

Rationale: Certain lung cancer patients express elevated Fucosyl Monosialoganglioside (Fuc-GM1) in circulation compared to control groups. Several sensitive methods involving characterization of Fuc-GM1 have been reported. However, a highly specific and sensitive method for quantifying multiple potential Fuc-GM1 biomarkers present in various biological matrices has not been reported to date.

Pharmacokinetic characterization of BMS-936561, an anti-CD70 antibody-drug conjugate, in preclinical animal species and prediction of its pharmacokinetics in humans.

CD70 is a tumor necrosis factor (TNF)-like type II integral membrane protein that is transiently expressed on activated T- and B-lymphocytes. Aberrant expression of CD70 was identified in both solid tumors and haematologic malignancies. BMS-936561 (αCD70_MED-A) is an antibody-drug conjugate composed of a fully human anti-CD70 monoclonal antibody (αCD70) conjugated with a duocarmycin derivative, MED-A, through a maleimide-containing citrulline-valine dipeptide linker.

Novel detection of DNA-alkylated adducts of antibody-drug conjugates with potentially unique preclinical and biomarker applications.

Background: MDX-1203 is an antibody-drug conjugate (ADC) currently in clinical trials for the treatment of renal carcinoma. The active ingredient of MDX-1203 is a DNA minor groove-binding cytotoxic drug that forms a covalently linked adduct with an adenine base. Formation of this adenine adduct prevents DNA replication, thus triggering cell death.

The impact of sex and contraceptive therapy on the plasma and intracellular pharmacokinetics of zidovudine.

Objectives: Zidovudine remains part of combination antiretroviral therapy. Pharmacological studies rely on quantitation of active triphosphates in peripheral blood mononuclear cells. This study evaluated the impact of female sex and contraceptive therapy on zidovudine plasma and intracellular pharmacokinetics and the impact of contraceptive therapy on HIV viral load.