Synthesis of pochoxime prodrugs as potent HSP90 inhibitors.

Pochoximes are potent inhibitors of heat shock protein 90 (HSP90) based on the radicicol pharmacophores. Herein we present a pharmacokinetics and pharmacodynamics evaluation of this compound series as well as a phosphate prodrug strategy to facilitate formulation and improve oral bioavailability.

Antitumor activity of a kinesin inhibitor.

Several members of the kinesin family of microtubule motor proteins play essential roles in mitotic spindle function and are potential targets for the discovery of novel antimitotic cancer therapies. KSP, also known as HsEg5, is a kinesin that plays an essential role in formation of a bipolar mitotic spindle and is required for cell cycle progression through mitosis. We identified a potent inhibitor of KSP, CK0106023, which causes mitotic arrest and growth inhibition in several human tumor cell lines.

Contribution of organic material to the ion composition of bone.

Studies of bone mineral ranging from cadaveric analysis to the use of high-resolution ion microprobe with secondary ion mass spectroscopy (SIMS) have concluded that bone is rich in sodium and potassium relative to calcium. Exposure of bone to acid conditions either in vitro or in vivo leads to an exchange of hydrogen ions for sodium and potassium buffering the acidity of the medium or blood, respectively. Whether these monovalent ions reside within the mineral or organic phases of bone has never been determined.

Effects of in vivo metabolic acidosis on midcortical bone ion composition.

Chronic metabolic acidosis increases urine calcium excretion without altering intestinal calcium absorption, suggesting that bone mineral is the source of the additional urinary calcium. During metabolic acidosis there appears to be an influx of protons into bone mineral, lessening the magnitude of the decrement in pH. Although in vitro studies strongly support a marked effect of metabolic acidosis on the ion composition of bone, there are few in vivo observations.

A secondary ion mass spectroscopic study of the elemental composition pattern in rat incisor dental enamel during different stages of ameloblast differentiation.

In most earlier studies on the elemental composition pattern of dental enamel, a picture is presented which describes a limited region. In this study, estimates of the incorporation of some critical elements into enamel were correlated with the differentiation stages of the ameloblasts through out the whole tooth. Elemental analyses of rat incisor dental enamel during the secretory, transitional and maturation phases were performed using two different modes of secondary ion mass spectrometry (SIMS).