Aug 8, 2013 - Type 2 diabetes is the most common form of diabetes, wherein the body develops insulin resistance or reduced insulin production, resulting in high blood glucose. Insulin secretagogues are used for effective control of insulin production
Aug 13, 2015 - Although there are a number of strategies aimed at treating HCC, including liver transplantation, radiofrequency ablation, and kinase inhibitor ...
In This Issue, Volume 4, Issue 8. Janice Elaine Y. Silverman. ACS Med. Chem. Lett. , 2013, 4 (8), pp 680â680. DOI: 10.1021/ml400268m. Publication Date ...
Jan 12, 2017 - Potential of Renal Outer Medullary Potassium (ROMK) Channel as Treatments for Hypertension and Heart Failure. ACS Medicinal Chemistry ...
Aug 8, 2013 - In This Issue, Volume 4, Issue 8. Janice Elaine Y. Silverman. ACS Med. Chem. Lett. , 2013, 4 (8), pp 680â680. DOI: 10.1021/ml400268m.
Jun 8, 2017 - Novel Potent and Selective Tricyclic Bruton's Tyrosine Kinase Inhibitors. Using Conformational Dynamics to Guide Selective Inhibitor ...
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Oct 12, 2017 - Auranofin, Et3PAuCl, and Et3PAuI Are Highly Cytotoxic on Colorectal Cancer Cells: A Chemical and Biological Study. ACS Medicinal ...
Nov 9, 2017 - Discovery of Indolinone-Based Multikinase Inhibitors as Potential Therapeutics for Idiopathic Pulmonary Fibrosis. ACS Medicinal Chemistry ...
In This Issue pubs.acs.org/acsmedchemlett
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A NOVEL SMALL MOLECULE THAT DISTINGUISHES HEALTHY CELLS FROM MELANOMA CELLS Active targeting involves the interaction of small molecules with receptors overexpressed on tumor cell surfaces. While some small molecules with active targeting properties have been identified, the repertoire has remained limited. In this issue, Burgess et al. (DOI: 10.1021/acsmedchemlett.6b00368) report the identification of novel targeting agents for metastatic melanoma. The authors prepared sets of bivalent pharmacophores containing a hydrophobic moiety and amino acids often found at protein−protein interfaces. These were subsequently combined with liposomes containing a plasmid encoding luciferase to identify molecules that bind specifically to cancer cells in a liposome assay. Further improvements of the molecules identified from the assay led to the discovery of a compound containing a near-IR aza-BODIPY fluor that exhibited specificity for melanoma cells both in vivo and in histology. This finding could lead to the development of drugs with improved efficacy for melanoma cells.
SYNTHESIS AND EVALUATION OF THIAZOLOQUINOLINONES WITH LINKERS TO ENABLE TARGETING OF CD38 The type II transmembrane glycoprotein CD38 is an ectoenzyme that exhibits both receptor and enzymatic function. CD38 is overexpressed on malignant plasma cells in multiple myeloma patients, thus making it an attractive pharmacological target. In this issue, McDonnell et al. (DOI: 10.1021/acsmedchemlett.6b00409) demonstrate the suitability of CD38 as a drug delivery and imaging target. The authors synthesized a series of thiazoloquinolinone analogues containing linkers that would allow for delivery of therapeutic payloads and imaging agents to cells overexpressing CD38. Subsequent SAR studies using surface plasmon resonance identified 4-cyclohexylamino analogues exhibiting affinity for CD38 and the potential for further functionalization. One analogue discovered in this study containing fluorescein bound to cells overexpressing CD38, illustrating the utility of thiazoloquinolinones as payloads for targeting CD38.
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PROFILING OF A THIOESTERASE REVERSIBLE INHIBITOR Activity-based protein profiling (ABPP) is a proteomic tool that applies chemical probes to the mechanistic study of related classes of enzymes in their native environment. This method rapidly transformed the discovery process of active-site ligands. However, efforts to identify reversible inhibitors with ABPP probes are less straightforward due to differences in inactivation rates and inhibitor displacement across enzyme families. In this issue, Martin et al. (DOI: 10.1021/acsmedchemlett.6b00441) describe their study on the selectivity of the acyl protein thioesterase 2 (APT2) reversible inhibitor ML349. Through biotinylation of ML349 and subsequent attachment to streptavidin resin, this affinity probe identified several targets outside of the serine hydrolase family. The study illustrates the caveat of solely focusing on in-class selectivity profiling, which may not identify off-target proteins.
