Boosting Affinity by Correct Ligand Preorganization for the S2 Pocket of Thrombin: A Study by Isothermal Titration Calorimetry, Molecular Dynamics, and High-Resolution Crystal Structures.

abstract：:A synthetic concept is presented that allows the construction of peptide isostere libraries through polymer-supported C-acylation reactions. A phosphorane linker reagent is used as a carbanion equivalent; by employing MSNT as a coupling reagent, the C-acylation can be conducted without racemization. Diastereoselective...

journal_title：ChemMedChem

authors： Weik S,Luksch T,Evers A,Böttcher J,Sotriffer CA,Hasilik A,Löffler HG,Klebe G,Rademann J

更新日期：2006-04-01 00:00:00

abstract：:Global pharmaceutical and biotechnology companies have been building increasingly on the skills and services offered by Indian biotech companies through strategic collaborative partnerships and alliances to fuel their in-house discovery and development pipelines. With the exception of generic press releases, however, ...

journal_title：ChemMedChem

authors： Differding E

更新日期：2014-01-01 00:00:00

abstract：:Cardiotoxicity is a common side effect of a large variety of drugs that is often caused by off-target human ether-à-go-go-related gene (hERG) potassium channel blockade. In this study, we designed and synthesized a series of derivatives of the class III antiarrhythmic agent E-4031. These compounds where evaluated in a...

journal_title：ChemMedChem

authors： Vilums M,Overman J,Klaasse E,Scheel O,Brussee J,IJzerman AP

更新日期：2012-01-02 00:00:00

abstract：:Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a small molecule with potent anticancer activity. Like other 1,4-naphthoquinones, it exhibits electrophilic reactivity towards biological nucleophiles. We demonstrate that plumbagin and structurally related 1,4-naphthoquinones with at least one unsubstituted quinoid...

journal_title：ChemMedChem

authors： Chrastina A,Welsh J,Rondeau G,Abedinpour P,Borgström P,Baron VT

更新日期：2020-07-20 00:00:00

abstract：:The histone methyltransferase SET7/9 methylates not only histone but also non-histone proteins as substrates, and therefore, SET7/9 inhibitors are considered candidates for the treatment of diseases. Previously, our group identified cyproheptadine, used clinically as a serotonin receptor antagonist and histamine recep...

journal_title：ChemMedChem

authors： Hirano T,Fujiwara T,Niwa H,Hirano M,Ohira K,Okazaki Y,Sato S,Umehara T,Maemoto Y,Ito A,Yoshida M,Kagechika H

更新日期：2018-08-10 00:00:00

abstract：:There is an urgent clinical need for imaging of α-synuclein (αSyn) fibrils, the hallmark biomarker for Parkinson's disease, in neurodegenerative disorders. Despite immense efforts, promising tracer candidates for nuclear imaging of αSyn are rare. Diphenyl pyrazoles are known modulators of αSyn aggregation and thus bea...

journal_title：ChemMedChem

authors： Maurer A,Leonov A,Ryazanov S,Herfert K,Kuebler L,Buss S,Schmidt F,Weckbecker D,Linder R,Bender D,Giese A,Pichler BJ,Griesinger C

更新日期：2020-03-05 00:00:00

abstract：:The molecular hybridization of different compounds with known pharmacological activity is a particularly prominent approach for the design of potential drugs with improved pharmacokinetic profiles. Much attention over the last decade has been focused on the synthesis of hybrid structures with a nitric oxide (NO)-donor...

journal_title：ChemMedChem

authors： Fershtat LL,Makhova NN

更新日期：2017-05-09 00:00:00

abstract：:TIBO- and TBO-like sulfone derivatives 1 and 2 were designed, synthesized, and tested for their ability to block the replication cycle of HIV-1 in infected cells. The anti-HIV-1 activities of sulfones 3, which were intermediates in the syntheses of 1 and 2, were also evaluated. Surprisingly, the sulfone analogues of T...

journal_title：ChemMedChem

authors： Di Santo R,Costi R,Artico M,Ragno R,Lavecchia A,Novellino E,Gavuzzo E,La Torre F,Cirilli R,Cancio R,Maga G

更新日期：2006-01-01 00:00:00

abstract：:We designed and synthesized two novel series of azapodophyllotoxin analogues as potential antivascular agents. A linker was inserted between the trimethoxyphenyl ring E and the tetracyclic ABCD moiety of the 4-aza-1,2-didehydropodophyllotoxins. In the first series, the linker enables free rotation between the two moie...

journal_title：ChemMedChem

authors： Labruère R,Gautier B,Testud M,Seguin J,Lenoir C,Desbène-Finck S,Helissey P,Garbay C,Chabot GG,Vidal M,Giorgi-Renault S

更新日期：2010-12-03 00:00:00

abstract：:Up to 45 % of deaths in developed nations can be attributed to chronic fibroproliferative diseases, highlighting the need for effective therapies. The RGD (Arg-Gly-Asp) integrin αvβ1 was recently investigated for its role in fibrotic disease, and thus warrants therapeutic targeting. Herein we describe the identificati...

journal_title：ChemMedChem

authors： Hatley RJD,Barrett TN,Slack RJ,Watson ME,Baillache DJ,Gruszka A,Washio Y,Rowedder JE,Pogány P,Pal S,Macdonald SJF

更新日期：2019-07-17 00:00:00

abstract：:Members of the Eph receptor tyrosine kinase family play essential roles in the pathogenesis of cancer and are therefore promising candidates for molecular imaging by positron emission tomography (PET), for example. In this regard, radiochemical access to novel PET radiotracers derived from potent inhibitors that targe...

journal_title：ChemMedChem

authors： Mamat C,Mosch B,Neuber C,Köckerling M,Bergmann R,Pietzsch J

更新日期：2012-11-01 00:00:00

abstract：:Disulfide bridges that stabilize the native conformation of conotoxins pose a challenge in the synthesis of smaller conotoxin analogues. Herein we describe the synthesis of a minimized analogue of the analgesic mu-conotoxin KIIIA that blocks two sodium channel subtypes, the neuronal Na(V)1.2 and skeletal muscle Na(V)1...

journal_title：ChemMedChem

authors： Han TS,Zhang MM,Walewska A,Gruszczynski P,Robertson CR,Cheatham TE 3rd,Yoshikami D,Olivera BM,Bulaj G

更新日期：2009-03-01 00:00:00

abstract：:The potassium channel openers flupirtine and retigabine have proven to be valuable analgesics or antiepileptics. Their recent withdrawal due to occasional hepatotoxicity and tissue discoloration, respectively, leaves a therapeutic niche unfilled. Metabolic oxidation of both drugs gives rise to the formation of electro...

journal_title：ChemMedChem

authors： Bock C,Surur AS,Beirow K,Kindermann MK,Schulig L,Bodtke A,Bednarski PJ,Link A

更新日期：2019-05-06 00:00:00

abstract：:Into the fold: Prion diseases are neurodegenerative disorders characterized by the accumulation in the brain of a self-replicating, misfolded isoform (PrPSc ) of the cellular prion protein (PrPC ). No therapies are available for these pathologies. We capitalized on previously described cell-based assays to screen a li...

journal_title：ChemMedChem

authors： Massignan T,Sangiovanni V,Biggi S,Stincardini C,Elezgarai SR,Maietta G,Andreev IA,Ratmanova NK,Belov DS,Lukyanenko ER,Belov GM,Barreca ML,Altieri A,Kurkin AV,Biasini E

更新日期：2017-08-22 00:00:00

abstract：:Drugs may have polypharmacological phenomena, that is, in addition to the desired target, they may also bind to many undesired or unknown physiological targets. As a result, they often exert side effects. In some cases, off-target interactions may lead to drug repositioning or to explaining a drug's mode of action. He...

journal_title：ChemMedChem

authors： Patel H,Lucas X,Bendik I,Günther S,Merfort I

更新日期：2015-07-01 00:00:00

abstract：:Pharmaceutical companies are facing an increasing interest in new target identification and validation. In particular, extensive efforts are being made in the field of protein kinase inhibitors research and development, and the past ten years of effort in this field have altered our perception of the potential of kina...

journal_title：ChemMedChem

authors： Margutti S,Laufer SA

更新日期：2007-08-01 00:00:00

abstract：:Given the number of monogenic ocular diseases and the number of non-monogenic degenerative ocular diseases for which gene therapy is considered as a treatment, the development of effective therapeutic delivery strategies for DNA is a critical research goal. In this work, nonviral nanoparticles (NPs) composed of glycol...

journal_title：ChemMedChem

authors： Mitra RN,Han Z,Merwin M,Al Taai M,Conley SM,Naash MI

更新日期：2014-01-01 00:00:00

abstract：:This paper describes the synthesis, characterisation, and cytotoxicity of a novel trinuclear platinum complex code named TH1. In addition to its activity against human ovarian cancer cell lines: A2780, A2780(cisR), and A2780(ZD0473R), cell uptake, DNA-binding, and the nature of the compound interaction with pBR322 pla...

journal_title：ChemMedChem

authors： Tayyem H,Huq F,Yu JQ,Beale P,Fisher K

更新日期：2008-01-01 00:00:00

abstract：:Nanoscale materials hold great promise in the therapeutic field. In particular, as carriers or vectors, they help bioactive molecules reach their primary targets. Furthermore, by themselves, certain nanomaterials-regarded as protective-can modulate particular metabolic pathways that are deregulated in pathological sit...

journal_title：ChemMedChem

authors： Bianco A,Muller S

更新日期：2016-01-19 00:00:00

abstract：:Targeting the biosynthetic pathway of neuroactive steroids with specific 18 kDa translocator protein (TSPO) ligands may be a viable therapeutic approach for a variety of neurodegenerative and neuropsychiatric diseases. However, the lack of correlation between binding affinity and in vitro steroidogenic efficacy has li...

journal_title：ChemMedChem

authors： Costa B,Taliani S,Da Pozzo E,Barresi E,Robello M,Cavallini C,Cosconati S,Da Settimo F,Novellino E,Martini C

更新日期：2017-08-22 00:00:00

abstract：:This is, to our knowledge, the most comprehensive analysis to date based on generative topographic mapping (GTM) of fragment-like chemical space (40 million molecules with no more than 17 heavy atoms, both from the theoretically enumerated GDB-17 and real-world PubChem/ChEMBL databases). The challenge was to prove tha...

journal_title：ChemMedChem

authors： Lin A,Horvath D,Afonina V,Marcou G,Reymond JL,Varnek A

更新日期：2018-03-20 00:00:00

abstract：:Three photoswitchable tetrapeptides, based on a known synthetic antibacterial, were designed and synthesized to determine activity against Staphylococcus aureus. Each peptide contains an azobenzene photoswitch incorporated into either the N-terminal side chain (1), C-terminal side chain (2), or the C-terminus (3) to a...

journal_title：ChemMedChem

authors： Yeoh YQ,Horsley JR,Yu J,Polyak SW,Jovcevski B,Abell AD

更新日期：2020-08-19 00:00:00

abstract：:The polyether ionophore salinomycin (SAL) has captured much interest because of its potent activity against cancer cells and cancer stem cells. Our previous studies have indicated that C1/C20 double-modification of SAL is a useful strategy to generate diverse agents with promising biological activity profiles. Thus, h...

journal_title：ChemMedChem

authors： Czerwonka D,Urbaniak A,Sobczak S,Piña-Oviedo S,Chambers TC,Antoszczak M,Huczyński A

更新日期：2020-01-17 00:00:00

abstract：:The β-site amyloid precursor protein cleaving enzyme 1 (BACE1, also known as β-secretase) is a promising target for the treatment of Alzheimer's disease. A pKa lowering approach over the initial leads was adopted to mitigate hERG inhibition and P-gp efflux, leading to the design of 6-CF3 dihydrothiazine 8 (N-(3-((4S,6...

journal_title：ChemMedChem

authors： Anan K,Iso Y,Oguma T,Nakahara K,Suzuki S,Yamamoto T,Matsuoka E,Ito H,Sakaguchi G,Ando S,Morimoto K,Kanegawa N,Kido Y,Kawachi T,Fukushima T,Teisman A,Urmaliya V,Dhuyvetter D,Borghys H,Austin N,Van Den Bergh A,Ver

更新日期：2019-11-20 00:00:00

abstract：:Targeting LRH-1: Virtual screening and molecular modeling were used to identify novel antagonists of liver receptor homolog-1 (LRH-1), an emerging therapeutic target for breast cancer. Hit compounds were synthesized and biologically assayed, and the preliminary results suggest that raloxifene-based analogues, substitu...

journal_title：ChemMedChem

authors： Rey J,Hu H,Kyle F,Lai CF,Buluwela L,Coombes RC,Ortlund EA,Ali S,Snyder JP,Barrett AG

更新日期：2012-11-01 00:00:00

abstract：:Vascular endothelial growth factor receptor 2 (VEGFR2) has been proven to play a major role in the regulation of tumor angiogenesis. A series of novel glycyrrhetic acid derivatives were synthesized and evaluated for their VEGFR2 inhibitory activity as well as their antiproliferative properties against four cancer cell...

journal_title：ChemMedChem

authors： Yan TL,Bai LF,Zhu HL,Zhang WM,Lv PC

更新日期：2017-07-06 00:00:00

abstract：:(±)-6-Alkyl-2,4-diaminopyrimidine-based inhibitors of bacterial dihydrofolate reductase (DHFR) have been prepared and evaluated for biological potency against Bacillus anthracis and Staphylococcus aureus. Biological studies revealed attenuated activity relative to earlier structures lacking substitution at C6 of the d...

journal_title：ChemMedChem

authors： Nammalwar B,Bourne CR,Bunce RA,Wakeham N,Bourne PC,Ramnarayan K,Mylvaganam S,Berlin KD,Barrow EW,Barrow WW

更新日期：2012-11-01 00:00:00

abstract：:In an approach to design drugs with higher affinity for π-π stacking and electrostatic interactions with targeted biomolecules, complexes of the type [{cis-Pt(A)2 (L)}2 -μ-{trans-1,4-dach}](NO3 )4 ((A)2 =(NH3 )2 or ethylenediamine (en), L=quinoline (quin) or benzothiazole (bztz), dach=trans-1,4-diaminocyclohexane) wer...

journal_title：ChemMedChem

authors： Ma ES,Daniel AG,Farrell NP

更新日期：2014-06-01 00:00:00

abstract：:Over the years, a number of dimensionality reduction techniques have been proposed and used in chemoinformatics to perform nonlinear mappings. In this study, four representatives of nonlinear dimensionality reduction methods related to two different families were analyzed: distance-based approaches (Isomap and Diffusi...

journal_title：ChemMedChem

authors： Kireeva NV,Ovchinnikova SI,Tetko IV,Asiri AM,Balakin KV,Tsivadze AY

更新日期：2014-05-01 00:00:00

abstract：:We previously described synapsin III (Syn III) as a synaptic phosphoprotein that controls dopamine release in cooperation with α-synuclein (aSyn). Moreover, we found that in Parkinson's disease (PD), Syn III also participates in aSyn aggregation and toxicity. Our recent observations point to threo-methylphenidate (MPH...

journal_title：ChemMedChem

authors： Casiraghi A,Longhena F,Straniero V,Faustini G,Newman AH,Bellucci A,Valoti E

更新日期：2020-07-20 00:00:00