Abstract:
:We report an advanced 'hybrid fingerprint' design concept specifically for the purpose of scaffold hopping. The generation of hybrid fingerprints includes two major steps. In the 'fingerprint reduction' step, bit positions of different types of fingerprints (e.g. substructural and pharmacophore fingerprints) are ranked according to their statistical significance and ability to discriminate between specifically active compounds and database decoys. On the basis of bit ranking, subsets containing the most discriminatory bit positions are determined. In the subsequent 'fingerprint recombination' step, bit subsets from different fingerprints are combined to yield a new compound class-directed fingerprint representation for similarity searching. Here, we generate hybrids from multiple fingerprints and analyze their search performance in comparison with parental fingerprints on compound activity classes that exclusively consist of molecules with unique core structures and that exhibit different levels of intra-class structural diversity. Fingerprint reduction is found to be a critical component of hybrid design. The resulting compound class-directed hybrid fingerprints further increase the similarity search performance and scaffold hopping potential of their parental fingerprints. Thus, fingerprint reduction and recombination improve compound recall and increase the structural diversity of hits.
journal_name
Chem Biol Drug Desjournal_title
Chemical biology & drug designauthors
Nisius B,Bajorath Jdoi
10.1111/j.1747-0285.2009.00930.xsubject
Has Abstractpub_date
2010-02-01 00:00:00pages
152-60issue
2eissn
1747-0277issn
1747-0285pii
JPP930journal_volume
75pub_type
杂志文章abstract::Bisphosphonates (BPs) have been commonly used in the treatment of osteolytic bone lesions, such as osteoporosis and osteogenesis imperfecta. However, serious side-effects can occur during the therapy. To search for novel potent BPs with lower side-effects, a series of imidazole-containing BPs (zoledronic acid [ZOL]; Z...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.13767
更新日期:2021-01-01 00:00:00
abstract::A novel series of thiophene-containing biaryl amide glucagon receptor (GCGR) antagonists were designed and synthesized. Two compounds of this series, 14f and 14h, exhibited good GCGR binding (IC50 = 6.1 and 4.4 μm, respectively) and cAMP functional activities (IC50 = 4.4 and 14.4 μm, respectively). The possible bind...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.13184
更新日期:2018-07-01 00:00:00
abstract::To address the problem of specificity in G-protein coupled receptor (GPCR) drug discovery, there has been tremendous recent interest in allosteric drugs that bind at sites topographically distinct from the orthosteric site. Unfortunately, structure-based drug design of allosteric GPCR ligands has been frustrated by th...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2010.01012.x
更新日期:2010-09-01 00:00:00
abstract::Previous reports describe modulators of X-linked inhibitor of apoptosis (XIAP)-caspase interaction designed from the AVPI N-terminal peptide sequence of second mitochondria-derived activator of caspase. A fragment-based drug design strategy was initiated to identify therapeutic non-peptidomimetic antagonists of X-link...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2009.00862.x
更新日期:2009-09-01 00:00:00
abstract::A new series of indole appended dihydronaphthalenone hybrid analogs (5a-t) have been synthesized through the Lewis acid catalyzed Michael addition of indoles to the arylidene/hetero arylidene ketones. All the synthesized derivatives are well characterized through the 1 H-NMR, 13 C-NMR, HRMS spectroscopic techniques, c...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12990
更新日期:2017-11-01 00:00:00
abstract::Two diazabicyclic analogues of ranolazine, (S,S,S)-5 and (S,S,R)-5, and their epimeric mixture were synthesized. Furthermore, their vasomotor effects on rat aorta rings precontracted with phenylephrine were analyzed. These compounds showed vasodilating effects significantly greater than ranolazine. The vasodilating ac...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12285
更新日期:2014-06-01 00:00:00
abstract::We report the first account of a comparative analysis of the binding affinities of nine FDA-approved drugs against subtype B as well as the South African subtype C HIV PR (C-SA). A standardized protocol was used to generate the inhibitor/C-SA PR complexes with the relative positions of the inhibitors taken from the co...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12063
更新日期:2013-02-01 00:00:00
abstract::Over the past decade, rapid development in biological and chemical technologies such as high-throughput screening, parallel synthesis, has been significantly increased the amount of data, which requires the creation and the integration of new analytical methods, especially deep learning models. Recently, there is an i...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.13742
更新日期:2020-09-01 00:00:00
abstract::Ecdysteroids initiate the molting process in insects by binding to the ecdysone receptor (EcR), which is a promising target for identifying insect growth regulators. This paper presents an in silico/in vitro screening procedure for identifying new EcR ligands. The three-step virtual screening procedure uses a three-di...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.13772
更新日期:2021-01-01 00:00:00
abstract::Chemotherapy against human African trypanosomiasis relies on four drugs that cause frequent and occasionally severe side-effects. Because human African trypanosomiasis is a disease of poor people in Africa, the traditional market-driven pathways to drug development are not available. One potentially rapid and cost-eff...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2006.00389.x
更新日期:2006-05-01 00:00:00
abstract::In an attempt to search for more potent positive inotropic agents, a series of N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(substitutedbenzyl-[1,4]diazepan-1-yl)acetamides were synthesized and evaluated for positive inotropic activity by measuring left atrium stroke volume in isolated rabbit heart p...
journal_title:Chemical biology & drug design
pub_type: 信件
doi:10.1111/j.1747-0285.2010.01057.x
更新日期:2011-01-01 00:00:00
abstract::N-type voltage-dependent Ca(2+) channels (CaV 2.2) are located at nerve endings in the central and peripheral nervous systems and are strongly associated with the pathological processes of cerebral ischaemia and neuropathic pain. CaV 2.2 blockers such as the ω-conotoxin MVIIA (Prialt) are analgesic and have opioid-spa...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12479
更新日期:2015-08-01 00:00:00
abstract::A series of novel triazolinones were synthesized and their structures were characterized by (1)H NMR, elemental analysis and single-crystal X-ray diffraction analysis. The herbicidal activities were evaluated against Echinochloa crusgalli (L.) Beauv., Digitaria adscendens, Brassica napus and Amaranthus retroflexus. Th...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2009.00819.x
更新日期:2009-06-01 00:00:00
abstract::The tumor suppressor gene, SMAD4, is mutated in approximately 30% of colon cancers. To identify compounds with enhanced potency on cells with a SMAD4-negative context, we combined genomic and cheminformatic analyses of publicly available data relating to the colon cancer cell lines within the NCI60 panel. Two groups o...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2010.00949.x
更新日期:2010-04-01 00:00:00
abstract::The development of isozyme-selective carbonic anhydrase inhibitors is currently still a great challenge. In the present study, protein-ligand complex structures were obtained by AutoDock Vina with SBR ((R)-N-(3-indol-1-yl-2-methyl-propyl)-4-sulfamoyl-benzamide) as the only inhibitor docked into the binding pockets of ...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12234
更新日期:2014-02-01 00:00:00
abstract::In this study, 3D-pharmacophore models of Aurora B kinase inhibitors have been developed by using HipHop and HypoGen modules in Catalyst software package. The best pharmacophore model, Hypo1, which has the highest correlation coefficient (0.9911), consists of one hydrogen-bond acceptor, one hydrogen-bond donor, one hy...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2008.00751.x
更新日期:2009-01-01 00:00:00
abstract::Hyperuricemia (HUA), a disease due to an elevation of body uric acid level and responsible for various diseases such as gout, cardiovascular disorders, and renal failure, is a major ground debate for the medical science these days. Considering the risk factors linked with allopathic drugs for the treatment of this dis...
journal_title:Chemical biology & drug design
pub_type: 杂志文章,评审
doi:10.1111/cbdd.13437
更新日期:2019-04-01 00:00:00
abstract::The cationic glycolipid IAXO-102, a potent TLR4 antagonist targeting both MD-2 and CD14 co-receptors, has been used as scaffold to design new potential TLR4 modulators and fluorescent labels for the TLR4 receptor complex (membrane TLR4.MD-2 dimer and CD14). The primary amino group of IAXO-102, not involved in direct i...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12749
更新日期:2016-08-01 00:00:00
abstract::Selective blockade of the serotonin 5-HT(2A) receptor is a useful therapeutic approach for a number of disorders, including schizophrenia, insomnia and ischaemic heart disease. A series of aporphines were docked into a homology model of the rat 5-HT(2A) receptor using AutoDock. Selected compounds with high in silico b...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12069
更新日期:2013-02-01 00:00:00
abstract::Quinacrine-the drug based on 9-aminoacridine-failed in clinical trials for prion diseases, whereas it was active in in vitro studies. We hypothesize that aromatic nucleophilic substitution at C9 could be contributing factor responsible for this failure because of the transfer of acridine moiety from quinacrine to abun...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12918
更新日期:2017-06-01 00:00:00
abstract::A series of 2-pyrimidinyl-piperazinyl-alkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione has been synthesized in an attempt to discover a new class of psychotropic agents. Compounds were evaluated for their in vitro affinity for serotonin 5-HT1A , 5-HT7 , and phosphodiesterases PDE4 and PDE10. The most pote...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.13442
更新日期:2019-04-01 00:00:00
abstract::A diversity of novel 2-aryl-3-heteroaryl-2-ylmethyl-1,3-thiazolidin-4-ones were designed and synthesized by reacting heteroaryl-2-ylmethyl amine with various 2,6-dihalosubstituted benzaldehydes and mercaptoacetic acid. The title compounds were evaluated for human immunodeficiency virus type-1 (HIV-1) reverse transcrip...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2008.00683.x
更新日期:2008-08-01 00:00:00
abstract::The diverse pharmacological properties of the diaryltriazenes have sparked the interest to investigate their potential to be repurposed as antitubercular drug candidates. In an attempt to improve the antitubercular activity of a previously constructed diaryltriazene library, eight new halogenated nitroaromatic triazen...
journal_title:Chemical biology & drug design
pub_type: 信件
doi:10.1111/cbdd.13087
更新日期:2018-02-01 00:00:00
abstract::Utilizing atypical wake-promoting agent modafinil (inactive in both rH(3) and hH(3) binding assays) as a launching pad, a series of sulfinyl- and sulfone-derived H(3) receptor inverse agonists were developed. Brain-permeable compound 27, a potent member of the series displayed excellent selectivity against related fam...
journal_title:Chemical biology & drug design
pub_type: 信件
doi:10.1111/cbdd.12094
更新日期:2013-03-01 00:00:00
abstract::Spiropyrans have been extensively investigated because of their thermo- and photochromic characteristics, but their biotherapeutic properties have not been explored much. We report anti-proliferative properties of a novel 3,3'-azadimethylene dinaphthospiropyran 11. Dibenzospiropyrans and dinaphthospiropyrans were synt...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.13785
更新日期:2021-02-01 00:00:00
abstract::We applied a novel molecular descriptor, three-dimensional biologically relevant spectrum (BRS-3D), in subtype selectivity prediction of dopamine receptor (DR) ligands. BRS-3D is a shape similarity profile calculated by superimposing the objective compounds against 300 template ligands from sc-PDB. First, we construct...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12815
更新日期:2016-12-01 00:00:00
abstract::The screening of an in-house quinolones library against Mycobacterium tuberculosis (Mtb) H(37) Rv, followed by a first cycle of optimization, yielded 6-hydrogen-8-methyl derivatives endowed with good potency. The antitubercular activity also encompassed the bacteria in a non-replicating state (NRP-TB) with minimum inh...
journal_title:Chemical biology & drug design
pub_type: 信件
doi:10.1111/cbdd.12022
更新日期:2012-11-01 00:00:00
abstract::A fullerene-isoniazid conjugate has been synthesized by 1, 3 dipolar cycloaddition reaction of fullerene (C(60)) with isonicotinic acid (4-formyl-benzylidene) hydrazide and N-methylglycine. The identity and purity of the compound was confirmed by elemental analysis, (1)H NMR, (13)C NMR and MALDI-TOF mass spectral anal...
journal_title:Chemical biology & drug design
pub_type: 信件
doi:10.1111/j.1747-0285.2009.00804.x
更新日期:2009-05-01 00:00:00
abstract::Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of the hematopoietic stem cells, characterized at the molecular level by the bcr/abl gene rearrangement. Even though targeting the fusion gene product Bcr-Abl protein is a successful strategy, development of drug resistance and that of drug intoler...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12983
更新日期:2017-10-01 00:00:00
abstract::Our previous studies have shown that geniposide plays an essential role in glucose-stimulated insulin secretion from pancreatic β cells and also regulates the metabolism of Aβ and its deposition in neurons. In this study, we reported that insulin deficiency induced significant increase of tau phosphorylation. Administ...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12673
更新日期:2016-03-01 00:00:00