Highly potent and selective ectonucleotide pyrophosphatase/phosphodiesterase I inhibitors based on an adenosine 5'-(α or γ)-thio-(α,β- or β,γ)-methylenetriphosphate scaffold.

Aberrant nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) activity is associated with chondrocalcinosis, osteoarthritis, and type 2 diabetes. The potential of NPP1 inhibitors as therapeutic agents, and the scarceness of their structure-activity relationship, encouraged us to develop new NPP1 inhibitors. Specifically, we synthesized ATP-α-thio-β,γ-CH2 (1), ATP-α-thio-β,γ-CCl2 (2), ATP-α-CH2-γ-thio (3), and 8-SH-ATP (4) and established their resistance to hydrolysis by NPP1,3 and NTPDase1,2,3,8 (<5% hydrolysis) (NTPDase = ectonucleoside triphosphate diphosphohydrolase).

Nonhydrolyzable ATP analogues as selective inhibitors of human NPP1: a combined computational/experimental study.

Elevated nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) activity is implicated in health disorders including pathological calcification. Specific NPP1 inhibitors would therefore be valuable for studying this enzyme and as potential therapeutic agents. Here we present a combined computational/experimental study characterizing 13 nonhydrolyzable ATP analogues as selective human NPP1 inhibitors.

Can myometrial electrical activity identify patients in preterm labor?

Objective: The objective of the study was to determine whether myometrial electrical activity can differentiate false from true preterm labor.

Study Design: Electrical uterine myography (EUM) was measured prospectively on 87 women, gestational age less than 35 weeks. The period between contractions, power of contraction peaks and movement of center of electrical activity (RMS), was used to develop an index score (1-5) for prediction of preterm delivery (PTD) within 14 days of the test.