Abstract:
:A common issue during drug design and development is the discovery of novel scaffolds for protein targets. On the one hand the chemical space of purchasable compounds is rather limited; on the other hand artificially generated molecules suffer from a grave lack of accessibility in practice. Therefore, we generated a novel virtual library of small molecules which are synthesizable from purchasable educts, called CHIPMUNK (CHemically feasible In silico Public Molecular UNiverse Knowledge base). Altogether, CHIPMUNK covers over 95 million compounds and encompasses regions of the chemical space that are not covered by existing databases. The coverage of CHIPMUNK exceeds the chemical space spanned by the Lipinski rule of five to foster the exploration of novel and difficult target classes. The analysis of the generated property space reveals that CHIPMUNK is well suited for the design of protein-protein interaction inhibitors (PPIIs). Furthermore, a recently developed structural clustering algorithm (StruClus) for big data was used to partition the sub-libraries into meaningful subsets and assist scientists to process the large amount of data. These clustered subsets also contain the target space based on ChEMBL data which was included during clustering.
journal_name
ChemMedChemjournal_title
ChemMedChemauthors
Humbeck L,Weigang S,Schäfer T,Mutzel P,Koch Odoi
10.1002/cmdc.201700689subject
Has Abstractpub_date
2018-03-20 00:00:00pages
532-539issue
6eissn
1860-7179issn
1860-7187journal_volume
13pub_type
杂志文章相关文献
ChemMedChem文献大全abstract::A small library of 17 organoruthenium compounds with the general formula [RuII (fcl)(chel)(L)]n+ (in which fcl=face capping ligand, chel=chelating bidentate ligand, and L=monodentate ligand) were screened for inhibitory activity against cholinesterases and glutathione-S-transferases of human and animal origins. Compou...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800432
更新日期:2018-10-22 00:00:00
abstract::Salecan is a water-soluble bacterial polysaccharide consisting of glucopyranosyl units linked by α-1,3 and β-1,3 glycosidic bonds. salecan is suitable for the development of hydrogels for biomedical applications, given its outstanding physicochemical and biological profiles. In this study we designed a new semi-interp...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600570
更新日期:2017-01-20 00:00:00
abstract::Antimicrobial peptides (AMPs) are promising candidates to help circumvent antibiotic resistance, which is an increasing clinical problem. Amino-terminal copper and nickel (ATCUN) binding motifs are known to actively form reactive oxygen species (ROS) upon metal binding. The combination of these two peptidic constructs...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402033
更新日期:2014-08-01 00:00:00
abstract::Herein we report the synthesis, photophysical properties, positron emission tomography (PET) imaging and photodynamic therapy (PDT) efficacy of methyl 3-(1'-m-iodobenzyloxy)ethyl-3-devinyl-verdin 4 (with or without the 124 I isotope). The PET imaging ability and ex vivo biodistribution of [124 I]4 were compared with t...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900352
更新日期:2019-08-20 00:00:00
abstract::Apelin is the endogenous ligand of the APJ receptor, a member of the G-protein-coupled receptor family. The apelin-APJ complex has been detected in many tissues and is emerging as a promising target for several pathophysiological conditions. There is currently little information on the structure-activity relationship ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201100492
更新日期:2012-02-06 00:00:00
abstract::Drug metabolism, toxicity, and their interaction profiles are major issues in the drug-discovery and lead-optimization processes. The cytochromes P450 (CYPs) 2D6 and 2C9 are enzymes involved in the oxidative metabolism of a majority of marketed drugs. Therefore, the prediction of the binding affinity towards CYP2D6 an...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201000358
更新日期:2010-12-03 00:00:00
abstract::Polo-like kinase 1 (PLK1) plays crucial functions in multiple stages of mitosis and is considered to be a potential drug target for cancer therapy. The functions of PLK1 are mediated by its N-terminal kinase domain and C-terminal polo-box domain (PBD). Most inhibitors targeting the kinase domain of PLK1 have a selecti...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402284
更新日期:2015-01-01 00:00:00
abstract::A hybrid approach was applied for the design of an inhibitor of trypsin-like serine proteases. Compound 16 [(R,R)- and (R,S)-diphenyl (4-(1-(4-amidinobenzylamino)-1-oxo-3-phenylpropan-2-ylcarbamoyl)phenylamino)(4-amidinophenyl)methylphosphonate hydrochloride], prepared in a convergent synthetic procedure, possesses a ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500319
更新日期:2015-10-01 00:00:00
abstract::β-Sheet antimicrobial peptides (AMPs) are well recognized as promising candidates for the treatment of multidrug-resistant bacterial infections. To dissociate antimicrobial activity and hemolytic effect of β-sheet AMPs, we hypothesize that N-methylation of the intramolecular hydrogen bond(s)-forming amides could impro...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300232
更新日期:2013-11-01 00:00:00
abstract::We report the synthesis of trifluoromethylated metallocenes (M=Fe, Ru) and related metal-free compounds for comparison of their biological properties with the aim to establish structure-activity relationships toward the anti-proliferative activity of this compound class. All new compounds were comprehensively characte...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402001
更新日期:2014-06-01 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
pub_type: 杂志文章
doi:10.1002/cmdc.201700561
更新日期:2018-03-20 00:00:00
abstract::The present work describes some recent approaches to novel 3-oxabicyclo[3.2.0]heptane-type nucleosides structurally similar to the potent anti-HIV agent stavudine (d4T). To gain knowledge at the molecular level relevant for further synthetic designs, the lack of activity of these compounds was investigated by computat...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200059
更新日期:2012-06-01 00:00:00
abstract::Having recently identified a so-far unexplored area adjacent to the known binding site of allosteric mitogen-activated protein kinase kinase (MEK) inhibitors, we now report an extension of these studies by combining our new side chains with different MEK inhibitor cores in a modular manner. Replacement of the amide he...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500442
更新日期:2015-12-01 00:00:00
abstract::Compound 11 (3-(benzyloxy)-1'-methyl-1'-azonia-4H-1'-azaspiro[isoxazole-5,3'-bicyclo[2.2.2]octane] iodide) was selected from a previous set of nicotinic ligands as a suitable model compound for the design of new silent agonists of α7 nicotinic acetylcholine receptors (nAChRs). Silent agonists evoke little or no channe...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700162
更新日期:2017-08-22 00:00:00
abstract::Protein-protein and protein-carbohydrate interactions as a means to target the cell surface for therapeutic applications have been extensively investigated. However, carbohydrate-carbohydrate interactions (CCIs) have largely been overlooked. Here, we investigate the concept of CCI-mediated drug delivery. Lactose-funct...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500046
更新日期:2015-05-01 00:00:00
abstract::A series of deuterated curcuminoids (CUR) were synthesized, bearing two to six OCD3 groups, in some cases in combination with methoxy groups, and in others together with fluorine or chlorine atoms. A model ring-deuterated hexamethoxy-CUR-BF2 and its corresponding CUR compound were also synthesized from a 2,4,6-trimeth...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900179
更新日期:2019-06-18 00:00:00
abstract::A series of water-soluble (benzoyloxy)methyl esters of acetylsalicylic acid (ASA), commonly known as aspirin, are described. The new derivatives each have alkyl chains containing a nitric oxide (NO)-releasing nitrooxy group and a solubilizing moiety bonded to the benzoyl ring. The compounds were synthesized and evalua...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300105
更新日期:2013-07-01 00:00:00
abstract::Modulating epigenetic mechanisms in malarial parasites is an emerging avenue for the discovery of novel antimalarial drugs. Previously we demonstrated the potent in vitro and in vivo antimalarial activity of (1-benzyl-4-piperidyl)[6,7-dimethoxy-2-(4-methyl-1,4-diazepin-1-yl)-4-quinazolinyl]amine (BIX01294; 1), a known...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402098
更新日期:2014-10-01 00:00:00
abstract::We synthesized potential inhibitors of farnesyl diphosphate synthase (FPPS), undecaprenyl diphosphate synthase (UPPS), or undecaprenyl diphosphate phosphatase (UPPP), and tested them in bacterial cell growth and enzyme inhibition assays. The most active compounds were found to be bisphosphonates with electron-withdraw...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600343
更新日期:2016-10-06 00:00:00
abstract::The ferrocenyl diphenol complexes 1,1-bis(4'-hydroxyphenyl)-2-ferrocenyl-but-1-ene (1) and 1,2-bis(4'-hydroxyphenyl)-1-ferrocenyl-but-1-ene [(Z)-2], which differ by the relative position of the two phenolic substituents, display dramatically different antiproliferative activities on cancer cells (1 is far more cytotox...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900430
更新日期:2019-10-04 00:00:00
abstract::LSD1 is a lysine demethylase highly involved in initiation and development of cancer. To design highly effective covalent inhibitors, a strategy is to fill its large catalytic cleft by designing tranylcypromine (TCP) analogs decorated with long, hindered substituents. We prepared three series of TCP analogs, carrying ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900730
更新日期:2020-04-03 00:00:00
abstract::The natural product piperlonguminine (PL) has been shown to exert potential anticancer activity against several types of cancer via elevation of reactive oxidative species (ROS). However, the application of PL has been limited due to its poor water solubility and moderate activity. To improve PL's potency, we designed...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000660
更新日期:2020-10-21 00:00:00
abstract::N-Myristoyltransferase (NMT) is a cytosolic monomeric enzyme present in eukaryotes such as fungi and protozoa, but is not found in prokaryotes. The attachment of a 14-carbon saturated fatty acid, myristate, from myristoyl-CoA (14:0 CoA) to the N-terminal glycine residue in a specific set of cellular proteins is common...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402174
更新日期:2014-11-01 00:00:00
abstract::Indolicidin (IR13), a 13-residue antimicrobial peptide from the cathelicidin family, is known to exhibit a broad spectrum of antimicrobial activity against various microorganisms. This peptide inhibits bacterial DNA synthesis resulting in cell filamentation. However, the precise mechanism remains unclear and requires ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402215
更新日期:2014-09-01 00:00:00
abstract::Cholesterol esterase (CEase), a serine hydrolase thought to be involved in atherogenesis and thus coronary heart disease, is considered as a target for inhibitor development. We investigated recombinant human and murine CEases with a new fluorometric assay in a structure-activity relationship study of a small library ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800388
更新日期:2018-09-06 00:00:00
abstract::A diverse group of proteins, the activities of which are precisely orchestrated during mitosis, have emerged as targets for cancer therapeutics; these include the Aurora kinases (AKs), Polo-like kinases (PLKs), and the kinesin spindle protein (KSP). KSP is essential for the proper separation of spindle poles during mi...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.201300228
更新日期:2013-11-01 00:00:00
abstract::A group of acidic nucleosides were synthesized to develop a new class of ribonuclease A (RNase A) inhibitors. Our recent study on carboxymethylsulfonyl-modified nucleosides revealed some interesting results in RNase A inhibition. This positive outcome triggered an investigation of the role played by secondary sugar hy...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402179
更新日期:2014-09-01 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
pub_type: 杂志文章
doi:10.1002/cmdc.200800292
更新日期:2009-03-01 00:00:00
abstract::Obesity is one of the main human epidemics today. The increase in fat accumulation, which is associated with obesity, may significantly change the expression of several bioactive molecules known as adipokines. These adipokines interact not only with adipose tissue, but also with metabolically relevant organs such as l...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.201200448
更新日期:2013-04-01 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
pub_type: 杂志文章
doi:10.1002/cmdc.200700204
更新日期:2008-01-01 00:00:00