Nonlinear dimensionality reduction for visualizing toxicity data: distance-based versus topology-based approaches.

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：:Two series of racemic goniothalamin analogues displaying nitrogen-containing groups were designed and synthesized. A total of 19 novel analogues were evaluated against a panel of four different cancer cell lines, along with the normal prostate cell line PNT2 to determine their selectivity. Among them, goniothalamin ch...

journal_title：ChemMedChem

authors： Meirelles MA,Braga CB,Ornelas C,Pilli RA

更新日期：2019-08-06 00:00:00

abstract：:Racemic 2-{[1-(chloromethyl)-5-nitro-3-{5-[2-(dimethylamino)ethoxy]indol-2-carbonyl}-1,2-dihydro-3H-benzo[e]indol-7-yl]sulfonyl}aminoethyl dihydrogen phosphate, a synthetic nitro derivative of the duocarmycins, is a hypoxia-selective prodrug active against radiation-resistant tumour cells at nontoxic doses in mice. An...

journal_title：ChemMedChem

authors： Tercel M,Lee HH,Yang S,Liyanage HD,Mehta SY,Boyd PD,Jaiswal JK,Tan KL,Pruijn FB

更新日期：2011-10-04 00:00:00

abstract：:Human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis belong to a group of infectious diseases known as neglected tropical diseases and are induced by infection with protozoan parasites named trypanosomatids. Drugs in current use have several limitations, and therefore new candidate drugs are required...

journal_title：ChemMedChem

authors： Dichiara M,Marrazzo A,Prezzavento O,Collina S,Rescifina A,Amata E

更新日期：2017-08-22 00:00:00

abstract：:A new class of imidazo[2,1-b]thiazole chalcone derivatives were synthesized and evaluated for their anticancer activity. These chalcone derivatives show promising activity, with log GI(50) values ranging from -7.51 to -4.00. The detailed biological aspects of these derivatives toward the MCF-7 cell line were studied. ...

journal_title：ChemMedChem

authors： Kamal A,Dastagiri D,Ramaiah MJ,Reddy JS,Bharathi EV,Srinivas C,Pushpavalli SN,Pal D,Pal-Bhadra M

更新日期：2010-11-08 00:00:00

abstract：:Modern organizations conducting drug-discovery programs frequently apply high-throughput screening to generate novel hit structures for the indications of interest. Systematic hit-to-lead processes have been established at most pharmaceutical companies to ensure a smooth conversion of hits into high-quality lead struc...

journal_title：ChemMedChem

authors： Steinmeyer A

更新日期：2006-01-01 00:00:00

abstract：:Prodrugs are effective tools in overcoming drawbacks typically associated with drug formulation and delivery. Those employing esterase-triggered functional groups are frequently utilized to mask polar carboxylic acids and phenols, increasing drug-like properties such as lipophilicity. Herein we detail a comprehensive ...

journal_title：ChemMedChem

authors： Perez C,Daniel KB,Cohen SM

更新日期：2013-10-01 00:00:00

abstract：:Opening up ion channels: We synthesised a series of anthraquinone analogues, called the GoSlo-SR family. Their effects on bladder smooth muscle BK channels were examined and, as shown, shifted voltage dependent activation >-100 mV (at 10 μM). They were more efficacious than NS11021 and could provide a new scaffold for...

journal_title：ChemMedChem

authors： Roy S,Morayo Akande A,Large RJ,Webb TI,Camarasu C,Sergeant GP,McHale NG,Thornbury KD,Hollywood MA

更新日期：2012-10-01 00:00:00

abstract：:Because only a few studies have investigated the affinity and functional activity of NMDA receptor open channel blockers under the same assay conditions, a comparative study of common open channel blockers is of major interest. The pharmacological activities of MK-801, phencyclidine (PCP), dexoxadrol, etoxadrol, (S)- ...

journal_title：ChemMedChem

authors： Temme L,Schepmann D,Schreiber JA,Frehland B,Wünsch B

更新日期：2018-03-06 00:00:00

abstract：:A series of new C13-triazole-bridged and C13-ether leucomycin analogues with a reduced aldehyde group were synthesized. Derivatives with the highest antibacterial [MIC values (S. epidermidis, S. pneumoniae): ∼2-4 μg mL(-1) ; 2.55-5.09 μm] and cytotoxic [IC50 values (HeLa, KB, MCF-7, A549, HepG2 cells): ∼1.35-3.70 μm] ...

journal_title：ChemMedChem

authors： Domagalska J,Janas A,Pyta K,Pecyna P,Ruszkowski P,Celewicz L,Gajecka M,Bartl F,Przybylski P

更新日期：2016-09-06 00:00:00

abstract：:In atomic force microscopy (AFM) a sharp cantilever tip is used to scan surfaces at the atomic level. One further application is force spectroscopy, in which force-distance curves between binding partners located on the cantilever and substrate surface are determined. This requires specifically immobilized molecules. ...

journal_title：ChemMedChem

authors： David R,Erdmann M,Fornof AR,Gaub HE

更新日期：2014-09-01 00:00:00

abstract：:Myotonic dystrophy is the most common form of adult-onset muscular dystrophy, originating in a CTG repeat expansion in the DMPK gene. The expanded CUG transcript sequesters MBNL1, a key regulator of alternative splicing, leading to the misregulation of numerous pre-mRNAs. We report an RNA-targeted agent as a possible ...

journal_title：ChemMedChem

authors： Luu LM,Nguyen L,Peng S,Lee J,Lee HY,Wong CH,Hergenrother PJ,Chan HY,Zimmerman SC

更新日期：2016-07-05 00:00:00

abstract：:Better control of postprandial hyperglycemia can be achieved by delaying the absorption of glucose resulting from carbohydrate digestion. Because α-amylase initiates the hydrolysis of polysaccharides, the design of α-amylase inhibitors can lead to the development of new treatments for metabolic disorders such as type ...

journal_title：ChemMedChem

authors： Al-Asri J,Gyémánt G,Fazekas E,Lehoczki G,Melzig MF,Wolber G,Mortier J

更新日期：2016-11-07 00:00:00

abstract：:Targeting the tumor cell mitochondrion could produce novel anticancer agents. We designed an aryl-urea fatty acid (1 g; 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid) that disrupted the mitochondrion and decreased MDA-MB-231 breast cancer cell viability. To optimize the aryl-ureas the prese...

journal_title：ChemMedChem

authors： Murray M,Roseblade A,Chen Y,Bourget K,Rawling T

更新日期：2020-01-17 00:00:00

abstract：:The concise synthesis and structure-activity relationship (SAR) studies of 3-aroylindoles were carried out in an effort to improve the potency and solubility of anticancer drug candidate BPR0L075 (8) by exploring structure modifications through three regimens: substitution of the B ring, at the N1 position, and of the...

journal_title：ChemMedChem

authors： Liou JP,Mahindroo N,Chang CW,Guo FM,Lee SW,Tan UK,Yeh TK,Kuo CC,Chang YW,Lu PH,Tung YS,Lin KT,Chang JY,Hsieh HP

更新日期：2006-10-01 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：:Two libraries, each consisting of 48 16beta-aminopropyl estradiol derivatives, phenols and sulfamates, respectively, were synthesized by solid-phase parallel chemistry through a seven-step reaction sequence. Following the attachment of a C18-steroid sulfamate precursor on a trityl chloride resin, diversity elements we...

journal_title：ChemMedChem

authors： Ciobanu LC,Poirier D

更新日期：2006-11-01 00:00:00

abstract：:The development and progression of chronic complications in diabetic patients, such as retinopathy, nephropathy, neuropathy, cataracts, and stroke, are related to the activation and/or overexpression of aldose reductase (ALR2), which is a member of the aldo-keto reductase superfamily. A structure-activity relationship...

journal_title：ChemMedChem

authors： Zhang S,Chen X,Parveen S,Hussain S,Yang Y,Jing C,Zhu C

更新日期：2013-04-01 00:00:00

abstract：:Nuclear magnetic resonance (NMR) spectroscopy is a valuable technique for ligand screening, because it exhibits high specificity toward chemical structure and interactions. Dissolution dynamic nuclear polarization (DNP) is a recent advance in NMR methodology that enables the creation of non-equilibrium spin states, wh...

journal_title：ChemMedChem

authors： Min H,Sekar G,Hilty C

更新日期：2015-09-01 00:00:00

abstract：:In the present study the importance of the active site histidine residue (His) for the activity of epoxide- or aziridine-based cysteine protease inhibitors is examined theoretically. To account for all important effects, QM/MM hybrid approaches are employed which combine quantum mechanical (QM) methods that are necess...

journal_title：ChemMedChem

authors： Mladenovic M,Schirmeister T,Thiel S,Thiel W,Engels B

更新日期：2007-01-01 00:00:00

abstract：:Schistosomiasis is a neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy relies on mass treatment with only one drug: praziquantel. Based on the 3-chlorobenzothiophene-2-hydroxamic acid J1075, a series of hydroxamic acids with different scaffolds were prep...

journal_title：ChemMedChem

authors： Bayer T,Chakrabarti A,Lancelot J,Shaik TB,Hausmann K,Melesina J,Schmidtkunz K,Marek M,Erdmann F,Schmidt M,Robaa D,Romier C,Pierce RJ,Jung M,Sippl W

更新日期：2018-08-10 00:00:00

abstract：:Abnormally high corticosteroid levels are responsible for the onset of serious hormone-related diseases, and the inhibition of their biosynthesis by targeting cytochrome P450 (CYP) isoforms CYP11B1 and CYP11B2 has emerged as a promising strategy to restore healthy physiological levels of corticosteroids. With the aim ...

journal_title：ChemMedChem

authors： Gobbi S,Hu Q,Zimmer C,Belluti F,Rampa A,Hartmann RW,Bisi A

更新日期：2016-08-19 00:00:00

abstract：:Silent Night: Antagonism of the orexin (or hypocretin) system has recently been identified as a novel mechanism for the treatment of insomnia. Herein, we describe discovery of a dual (OX(1)R/OX(2)R) orexin receptor antagonist featuring a 1,4-diazepane central constraint that blocks orexin signaling in vivo. In telemet...

journal_title：ChemMedChem

authors： Whitman DB,Cox CD,Breslin MJ,Brashear KM,Schreier JD,Bogusky MJ,Bednar RA,Lemaire W,Bruno JG,Hartman GD,Reiss DR,Harrell CM,Kraus RL,Li Y,Garson SL,Doran SM,Prueksaritanont T,Li C,Winrow CJ,Koblan KS,Renger JJ,C

更新日期：2009-07-01 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：:Histone deacetylases (HDACs) are promising drug targets for a variety of therapeutic applications. Herein we describe the design, synthesis, biological evaluation in cellular models of cancer, and preliminary drug metabolism and pharmacokinetic studies (DMPK) of a series of secondary and tertiary N-substituted 7-amino...

journal_title：ChemMedChem

authors： Abdelkarim H,Neelarapu R,Madriaga A,Vaidya AS,Kastrati I,Karumudi B,Wang YT,Taha TY,Thatcher GRJ,Frasor J,Petukhov PA

更新日期：2017-12-19 00:00:00

abstract：:Herein we describe the synthesis and conformational analysis of a series of bicyclic thymidine derivatives and their evaluation as inhibitors of thymidine monophosphate kinase from Mycobacterium tuberculosis (TMPKmt), based on previously discovered bicyclic sugar nucleosides. With a K(i) value of 2.3 microm, 1-[3-amin...

journal_title：ChemMedChem

authors： Van Daele I,Munier-Lehmann H,Hendrickx PM,Marchal G,Chavarot P,Froeyen M,Qing L,Martins JC,Van Calenbergh S

更新日期：2006-10-01 00:00:00

abstract：:The global fight to stop tuberculosis (TB) remains a great challenge, particularly with the increase in drug-resistant strains and a lack of funding to support the development of new treatments. To bolster a precarious drug pipeline, we prepared a focused panel of eight pentafluorosulfanyl (SF5 ) compounds which were ...

journal_title：ChemMedChem

authors： Moraski GC,Bristol R,Seeger N,Boshoff HI,Tsang PS,Miller MJ

更新日期：2017-07-20 00:00:00

abstract：:Leishmaniasis is a complex disease caused by over 20 Leishmania species that primarily affects populations with poor socioeconomic conditions. Currently available drugs for treating leishmaniasis include amphotericin B, paromomycin, and pentavalent antimonials, which have been associated with several limitations, such...

journal_title：ChemMedChem

authors： Herrera-Acevedo C,Perdomo-Madrigal C,Muratov EN,Scotti L,Scotti MT

更新日期：2020-12-17 00:00:00

abstract：:Aberrant WNT pathway activation, leading to nuclear accumulation of β-catenin, is a key oncogenic driver event. Mutations in the tumor suppressor gene APC lead to impaired proteasomal degradation of β-catenin and subsequent nuclear translocation. Restoring cellular degradation of β-catenin represents a potential thera...

journal_title：ChemMedChem

authors： Kessler D,Mayer M,Zahn SK,Zeeb M,Wöhrle S,Bergner A,Bruchhaus J,Ciftci T,Dahmann G,Dettling M,Döbel S,Fuchs JE,Geist L,Hela W,Kofink C,Kousek R,Moser F,Puchner T,Rumpel K,Scharnweber M,Werni P,Wolkerstorfer B,

更新日期：2020-12-04 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