Discovery of TP0628103: A Highly Potent and Selective MMP-7 Inhibitor with Reduced OATP-Mediated Clearance Designed by Shifting Isoelectric Points.

Matrix metalloproteinase-7 (MMP-7) has been shown to play an important role in pathophysiological processes such as cancer and fibrosis. We previously discovered selective MMP-7 inhibitors by molecular hybridization and structure-based drug design. However, the systemic clearance (CL) of the biologically active lead compound was very high.

Discovery of novel indole derivatives as potent and selective inhibitors of proMMP-9 activation.

Matrix metalloproteinase-9 (MMP-9) is a secreted zinc-dependent endopeptidase that degrades the extracellular matrix and basement membrane of neurons, and then contributes to synaptic plasticity by remodeling the extracellular matrix. Inhibition of MMP-9 activity has therapeutic potential for neurodegenerative diseases such as fragile X syndrome. This paper reports the molecular design, synthesis, and in vitro studies of novel indole derivatives as inhibitors of proMMP-9 activation.

Structure-Based Optimization and Biological Evaluation of Potent and Selective MMP-7 Inhibitors for Kidney Fibrosis.

Matrix metalloproteinase-7 (MMP-7) has been shown to play important roles in pathophysiological processes involved in the development/progression of diseases such as cancer and fibrosis. We discovered selective MMP-7 inhibitors composed of arylsulfonamide, carboxylate, and short peptides by a molecular hybridization approach. These compounds interacted with MMP-7 via multiple hydrogen bonds in the cocrystal structures.

Single-carbon atom transfer to α,β-unsaturated amides from N-heterocyclic carbenes.

Single-carbon atom transfer reactions are lacking in organic synthesis, partly because of the absence of atomic carbon sources under standard solution-phase conditions. We report here that N-heterocyclic carbenes can serve as atomic carbon donors through the loss of a 1,2-diimine moiety. This strategy is applicable to single-carbon atom transfer to α,β-unsaturated amides, which can be converted into homologated γ-lactams through the formation of four single bonds to one carbon center in one operation.

Feasibility study of direct CT lymphangiography in mice: comparison with interstitial CT/MR lymphangiography.

Objectives: To establish a CT lymphangiography method in mice via direct lymph node puncture.

Methods: We injected healthy mice (n = 8) with 50 µl of water-soluble iodine contrast agent (iomeprol; iodine concentration, 350 mg/mL) subcutaneously into the left-rear foot pad (interstitial injection) and 20 µl of the same contrast agent directly into the popliteal lymph node (direct puncture) 2 days later. Additionally, we performed interstitial MR lymphangiography on eight mice as a control group.