WAY 170523

Description:IC50: 17 nm (MMP-13)
Collagenase 3 is an enzyme that in humans is encoded by the MMP13 gene. Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis .
In vitro: The combination of NMR spectroscopy with molecular modeling techniques and HTS data resulted in the design of a novel, potent, and selective MMP-13 inhibitor (WAY-170523) which has an IC50 of 17 nM for MMP-13 and showed >5800-, 56-, and >500-fold selectivity against MMP-1, MMP-9, and TACE, respectively. To the best of our knowledge, this represents the first example of a potent MMP-13 inhibitor that has been shown to be selective against MMP-9 [1].
In vivo: In order to investigate a putative role of MMP-13 in ISO-dependent cardiac dysfunction, the authors infused WT mice with ISO for 7 days and concurrently delivered the specific MMP-13 inhibitor WAY170523 daily by i.p injection. Remarkably, they found that WAY170523 completely abolished ISO-dependent increase of the left ventricular systolic diameter and preserved cardiac function in ISO-infused animals without modifying the hypertrophic response similar to the PAR1 KO animals. [2].
Clinical trial: WAY-170523 is currently in the preclinical development and no clinical trial is ongoing.
References:
[1] James M. Chen, Frances C. Nelson, Jeremy I. Levin, Dominick Mobilio, Franklin J. Moy, Ramaswamy Nilakantan, Arie Zask, and Robert Powers. Structure-Based Design of a Novel, Potent, and Selective Inhibitor for MMP-13 Utilizing NMR Spectroscopy and Computer-Aided Molecular Design. J. Am. Chem. Soc. 2000, 122, 9648-9654
[2] Jaffré F, Friedman AE, Hu Z, Mackman N, Blaxall BC. β-adrenergic receptor stimulation transactivates protease-activated receptor 1 via matrix metalloproteinase 13 in cardiac cells. Circulation. 2012;125(24):2993-3003.

The problem of choice: From the voluntary way to Affordable Care Act health insurance exchanges.[Pubmed:28371627]

Soc Sci Med. 2017 May;181:34-42.

This article takes a genealogical and ethnographic approach to the problem of choice, arguing that what choice means has been reworked several times since health insurance first figured prominently in national debates about health reform. Whereas voluntary choice of doctor and hospital used to be framed as an American right, contemporary choice rhetoric includes consumer choice of insurance plan. Understanding who has deployed choice rhetoric and to what ends helps explain how offering choices has become the common sense justification for defending and preserving the exclusionary health care system in the United States. Four case studies derived from 180 enrollment observations at the Rhode Island health insurance exchange conducted from March 2014-January 2017 and interviews with enrollees show how choice is experienced in this latest iteration of health reform. The Affordable Care Act (ACA) of 2010 created new pathways to insurance coverage in the United States. Insurance exchanges were supposed to unleash the power of consumer decision-making through marketplaces where health plans compete on quality, coverage, and price. Consumers, however, contended with confusing insurance terminology and difficult to navigate websites. The ethnography shows that consumers experienced choice as confusing and overwhelming and did not feel "in charge" of their decisions. Instead, unstable employment, changes in income, existing health needs, and bureaucratic barriers shaped their "choices."

DNA Three-Way Junction for Differentiation of Single-Nucleotide Polymorphisms with Fluorescent Copper Nanoparticles.[Pubmed:28370648]

Chemistry. 2017 May 23;23(29):6979-6982.

A label- and enzyme-free fluorescent sensor for the detection of single-nucleotide polymorphisms (SNPs) at room temperature is proposed, using new copper nanoparticles (CuNPs) as fluorescent reporters. The CuNPs were constructed by using a DNA three-way junction (3WJ) template. In this assay, two complementary adenine/thymine-rich probes can hybridize with the wild-type target simultaneously to construct a 3WJ structure, serving as an efficient scaffold for the generation of CuNPs. However, the CuNPs produce weak fluorescence when the probes bind with a mutant-type target. SNPs can be identified by the difference in fluorescence intensity of the CuNPs. This SNPs detection strategy is straightforward, cost-effective, and avoids the complicated procedures of labeling or enzymatic reactions. The fluorescent sensor is versatile and can be applied to all types of mutation because the probes are programmable. Moreover, the sensor exhibits good detection performance in biological samples.