Abstract:
:[This corrects the article DOI: 10.1021/acsmedchemlett.9b00612.].
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
Kaiser TM,Dentmon ZW,Dalloul CE,Sharma SK,Liotta DCdoi
10.1021/acsmedchemlett.0c00336subject
Has Abstractpub_date
2020-06-24 00:00:00pages
1491issue
7issn
1948-5875journal_volume
11pub_type
已发布勘误abstract::Abdominal pain and abnormal bowel habits represent major symptoms for irritable bowel syndrome (IBS) patients that are not adequately managed. Although the etiology of IBS is not completely understood, many of the functions of the gastrointestinal (GI) tract are regulated by the enteric nervous system (ENS). Inflammat...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.8b00035
更新日期:2018-05-24 00:00:00
abstract::Protein kinases are key regulators that govern complex cellular processes. Dysregulation of kinase signaling is associated in many human diseases, particularly cancers and developmental and metabolic disorders. Tyrosine kinase inhibitors have achieved great success in molecular targeted therapies for cancer and now is...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml500091p
更新日期:2014-03-06 00:00:00
abstract::A new series of potent TG2 inhibitors are reported that employ a 4-aminopiperidine core bearing an acrylamide warhead. We establish the structure-activity relationship of this new series and report on the transglutaminase selectivity and in vitro ADME properties of selected compounds. We demonstrate that the compounds...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml3001352
更新日期:2012-08-09 00:00:00
abstract::Recently, the binding kinetics of a ligand-target interaction, such as the residence time of a small molecule on its protein target, are seen as increasingly important for drug efficacy. Here, we investigate these concepts to explain binding and proton blockage of rimantadine variants bearing progressively larger alky...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.7b00458
更新日期:2018-01-29 00:00:00
abstract::We report the discovery of a new (S)-3-aminopyrrolidine series of CCR2 antagonists. Structure-activity relationship studies on this new series led to the identification of 17 (INCB8761/PF-4136309) that exhibited potent CCR2 antagonistic activity, high selectivity, weak hERG activity, and an excellent in vitro and in v...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml200199c
更新日期:2011-10-05 00:00:00
abstract::A new class of 4-aminoquinolines was synthesized and evaluated in vitro for antiplasmodial activity against both the chloroquine-sensitive (3D7) and -resistant (K1 and W2) strains. The most active compounds 3c-3e had acceptable cytotoxicity but showed strong inhibition toward a panel of cytochrome P450 enzymes in vitr...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml400311r
更新日期:2013-10-01 00:00:00
abstract::Bacterial RNA polymerase (RNAP) is essential for transcription and is an antibacterial target for small molecule inhibitors. The binding region of myxopyronin B (MyxB), a bacterial RNAP inhibitor, offers the possibility of new inhibitor design. The molecular design program SPROUT has been used in conjunction with the ...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml200087m
更新日期:2011-07-29 00:00:00
abstract::CREB (cAMP response element binding protein) has been shown to play an important role in tumor initiation, progression, and metastasis. We discovered that naphthol AS-E, a cell-permeable CREB inhibitor, presented antiproliferative activity in a broad panel of cancer cell lines in vitro. However, it has limited aqueous...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml500330n
更新日期:2014-08-22 00:00:00
abstract::Inhibition of the lipid kinase PI3Kδ is a promising principle to treat B and T cell driven inflammatory diseases. Using a scaffold deconstruction-reconstruction strategy, we identified 4-aryl quinazolines that were optimized into potent PI3Kδ isoform selective analogues with good pharmacokinetic properties. With compo...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.6b00119
更新日期:2016-06-02 00:00:00
abstract::The atypical chemokine receptor CXCR7 has been studied in various disease settings including immunological diseases and heart disease. Efforts to elucidate the role of CXCR7 have been limited by the lack of suitable chemical tools with a range of pharmacological profiles. A high-throughput screen was conducted to disc...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.0c00163
更新日期:2020-05-14 00:00:00
abstract::Despite several years of research, only a handful of β-secretase (BACE) 1 inhibitors have entered clinical trials as potential therapeutics against Alzheimer's disease. The intrinsic basic nature of low molecular weight, amidine-containing BACE 1 inhibitors makes them far from optimal as central nervous system drugs. ...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.9b00181
更新日期:2019-07-02 00:00:00
abstract::Neuromedin U (NMU) and S (NMS) display various physiological activities, including an anorexigenic effect, and share a common C-terminal heptapeptide-amide sequence that is necessary to activate two NMU receptors (NMUR1 and NMUR2). On the basis of this knowledge, we recently developed hexapeptide agonists 2 and 3, whi...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml500494j
更新日期:2015-01-28 00:00:00
abstract::A series of potent and selective β1-adrenoreceptor ligands were identified (IC50 range, 0.04-0.25 nM; β1/β2 selectivity range, 65-450-fold), labeled with the PET radioisotope fluorine-18 and evaluated in normal Sprague-Dawley rats. Tissue distribution studies demonstrated uptake of each radiotracers from the blood poo...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml1002458
更新日期:2011-07-22 00:00:00
abstract::The acyldepsipeptide (ADEP) antibiotics operate through a clinically unexploited mechanism of action and thus have attracted attention from several antibacterial development groups. The ADEP scaffold is synthetically tractable, and deep-seated modifications have produced extremely potent antibacterial leads against Gr...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.7b00320
更新日期:2017-10-19 00:00:00
abstract::A series of TRPA1 antagonists is described which has as its core structure an indazole moiety. The physical properties and in vitro DMPK profiles are discussed. Good in vivo exposure was obtained with several analogs, allowing efficacy to be assessed in rodent models of inflammatory pain. Two compounds showed signific...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.7b00140
更新日期:2017-05-18 00:00:00
abstract::We have developed a novel albumin-binding prodrug of doxorubicin that incorporates p-aminobenzyloxycarbonyl (PABC) as a 1,6 self-immolative spacer in addition to the heptapeptide, Arg-Ser-Ser-Tyr-Tyr-Ser-Leu, as a substrate for the prostate-specific antigen (PSA) that is overexpressed in prostate carcinoma and represe...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml100060m
更新日期:2010-05-26 00:00:00
abstract::A new series of 1,4-naphthoquinones, bearing various cyclic and aliphatic amines on C2, was designed and synthesized to identify antiproliferative agents for triple-negative breast cancer, which represents a clinical challenge without targeted therapies. Among naphthoquinones, 2a and 3a inhibited the proliferation of ...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.8b00333
更新日期:2019-02-15 00:00:00
abstract::Herein we describe the discovery of A-1331852, a first-in-class orally active BCL-XL inhibitor that selectively and potently induces apoptosis in BCL-XL-dependent tumor cells. This molecule was generated by re-engineering our previously reported BCL-XL inhibitor A-1155463 using structure-based drug design. Key design ...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.9b00568
更新日期:2020-03-30 00:00:00
abstract::Cellular proteins that fail to fold properly result in inactive or disfunctional proteins that can have toxic functions. The unfolded protein response (UPR) is a two-tiered cellular mechanism initiated by eukaryotic cells that have accumulated misfolded proteins within the endoplasmic reticulum (ER). An adaptive pathw...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml5003234
更新日期:2014-10-29 00:00:00
abstract::A novel series of alkoxyimino derivatives as S1P1 agonists were discovered through de novo design using FTY720 as the chemical starting point. Extensive structure-activity relationship studies led to the discovery of (E)-1-(4-(1-(((4-cyclohexyl-3-(trifluoromethyl)benzyl)oxy)imino)ethyl)-2-ethylbenzyl)azetidine-3-carbo...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml300396r
更新日期:2013-01-04 00:00:00
abstract::The renal outer medullary potassium channel (ROMK or Kir1.1) is a putative drug target for a novel class of diuretics that could be used for the treatment of hypertension and edematous states such as heart failure. An internal high-throughput screening campaign identified 1,4-bis(4-nitrophenethyl)piperazine (5) as a p...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml3000066
更新日期:2012-03-28 00:00:00
abstract::The selectivity of histone deacetylase inhibitors (HDACis) is greatly impacted by the zinc binding groups. In an effort to search for novel zinc binding groups, we applied a parallel medicinal chemistry (PMC) strategy to quickly synthesize substituted benzamide libraries. We discovered a series containing 2-substitute...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.0c00462
更新日期:2020-10-13 00:00:00
abstract::Membrane-bound pyrophosphatases (mPPases) regulate energy homeostasis in pathogenic protozoan parasites and lack human homologues, which makes them promising targets in e.g. malaria. Yet only few nonphosphorus inhibitors have been reported so far. Here, we explore an isoxazole fragment hit, leading to the discovery of...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.9b00537
更新日期:2020-02-17 00:00:00
abstract::Synthesis of a strict structural analogue of albaconazole in which the quinazolinone ring is fused by a thiazole moiety led to the discovery of a new triazole with broad-spectrum antifungal activity. Compound I exhibited high in vitro activity against pathogenic Candida species and filamentous fungi and showed prelimi...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml300429p
更新日期:2013-01-17 00:00:00
abstract::Somatic point mutations at a key arginine residue (R132) within the active site of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) confer a novel gain of function in cancer cells, resulting in the production of d-2-hydroxyglutarate (2-HG), an oncometabolite. Elevated 2-HG levels are implicated in epigenetic alt...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.7b00421
更新日期:2018-01-19 00:00:00
abstract::A series of bis(l-amino acid) ester prodrugs of tenofovir (TFV) were designed and synthesized as new anti-HBV agents in this work. Four compounds 11, 12a, 12d, and 13b displayed better anti-HBV activity (IC50: 0.71-4.22 μM) than the parent drug TFV. The most active compound 11 (IC50: 0.71 μM), a bis(l-valine) ester pr...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.9b00184
更新日期:2019-05-16 00:00:00
abstract::The multistep preparation of (11)C-levetiracetam ((11)C-LEV) was carried out by a one-pot radiosynthesis with 8.3 ± 1.6% (n = 8) radiochemical yield in 50 ± 5.0 min. Briefly, the propionaldehyde was converted to propan-1-imine in situ as labeling precursor by incubation with ammonia. Without further separation, the im...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml500285t
更新日期:2014-08-19 00:00:00
abstract::The polyether ionophore salinomycin has recently gained attention due to its exceptional ability to selectively reduce the proportion of cancer stem cells within a number of cancer cell lines. Efficient single step strategies for the preparation of hydroxamic acid hybrids of this compound varying in N- and O-alkylatio...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.6b00079
更新日期:2016-04-25 00:00:00
abstract::With only two new classes of antibiotics developed in the last 40 years, novel antibiotics are desperately needed to combat the growing problem of multidrug-resistant and extensively drug resistant bacteria, particularly Gram-negative bacteria. Described in this letter is the synthesis and antibiotic activity of 1,2,4...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.6b00296
更新日期:2016-11-12 00:00:00
abstract::In this study the μ opioid receptor (MOR) ligands DALDA (Tyr-d-Arg-Phe-Lys-NH2) and Dmt1-DALDA (Dmt-d-Arg-Phe-Lys-NH2, Dmt = 2',6'-dimethyltyrosine) were glycosylated at the N- or C-terminus. Subsequently, the modified peptides were subjected to in vitro and in vivo evaluation. In contrast to the N-terminally modified...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml4004765
更新日期:2014-04-10 00:00:00