Abstract:
:Interstitial cystitis/painful bladder syndrome is a chronic bladder disorder with epithelial thinning or ulceration, pain, urinary frequency and urgency, for which there is no reliably effective therapy. We previously reported that interstitial cystitis/painful bladder syndrome bladder epithelial cells make a glycopeptide antiproliferative factor or 'APF' (Neu5Acα2-3Galβ1-3GalNAcα-O-TVPAAVVVA) that induces abnormalities in normal cells similar to those in interstitial cystitis/painful bladder syndrome cells in vitro, including decreased proliferation, decreased tight junction formation, and increased paracellular permeability. We screened inactive APF derivatives for their ability to block antiproliferative activity of asialylated-APF ('as-APF') in normal bladder cells and determined the ability of as-APF-blocking derivatives to normalize tight junction protein expression, paracellular permeability, and/or proliferation of interstitial cystitis/painful bladder syndrome cells. Only two of these derivatives [Galβ1-3GalNAcα-O-TV-(d-pipecolic acid)-AAVVVA and Galβ1-3GalNAcα-O-TV-(d-proline)-AAVVVA] blocked as-APF antiproliferative activity in normal cells (p < 0.001 for both). Both of these antagonists also 1) significantly increased mRNA expression of ZO-1, occludin, and claudins 1, 4, 8, and 12 in interstitial cystitis/painful bladder syndrome cells by qRT-PCR; 2) normalized interstitial cystitis/painful bladder syndrome epithelial cell tight junction protein expression and tight junction formation by confocal immunofluorescence microscopy; and 3) decreased paracellular permeability of (14) C-mannitol and (3) H-inulin between confluent interstitial cystitis/painful bladder syndrome epithelial cells on Transwell plates, suggesting that these potent APF antagonists may be useful for the development as interstitial cystitis/painful bladder syndrome therapies.
journal_name
Chem Biol Drug Desjournal_title
Chemical biology & drug designauthors
Keay S,Kaczmarek P,Zhang CO,Koch K,Szekely Z,Barchi JJ Jr,Michejda Cdoi
10.1111/j.1747-0285.2011.01108.xsubject
Has Abstractpub_date
2011-06-01 00:00:00pages
421-30issue
6eissn
1747-0277issn
1747-0285journal_volume
77pub_type
杂志文章abstract::Artemisinin is a naturally occurring antimalarial agent which has shown potent anticancer activity. In this work, new artemisinin derivatives with the piperazine group were synthesized. The cytotoxic activities of derivatives 5a-5d were evaluated by MTT assay against ten cell lines. The results showed that 5a-5d were ...
journal_title:Chemical biology & drug design
pub_type: 信件
doi:10.1111/cbdd.13016
更新日期:2017-11-01 00:00:00
abstract::A series of novel C-aryl glucosides with substituents at the 3'-position or cyclization at 3', 4'-positions of the distal aryl ring were designed and synthesized, which might decrease the oxidative metabolism of dapagliflozin. Preliminary evaluation for hypoglycemic effect and the risk of hypoglycemia were carried out...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12547
更新日期:2015-10-01 00:00:00
abstract::A large number of chemotherapeutic drugs, utilized in the treatment of advanced metastatic clear cell renal cell carcinoma, are typically prone to poor biocompatibility, lack of targeting specificity, and high toxicity, which mostly leads to unsatisfactory clinical outcomes. As a new drug delivery pathway, nanoliposom...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.13652
更新日期:2020-03-01 00:00:00
abstract::Anthranilic diamides is a class of insecticides target at ryanodine receptors (RyRs). To discover potent insecticides targeting at RyRs, a series of novel anthranilic diamides with a diacylhydrazine bridge were designed and synthesized. Their insecticidal activities were evaluated and a preliminary structure-activity ...
journal_title:Chemical biology & drug design
pub_type: 信件
doi:10.1111/cbdd.13349
更新日期:2018-11-01 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::Somatostatin owes its biological activity to the presence of a well-defined beta-turn centered around the tetrapeptide Phe-Trp-Lys-Thr. We have developed a light-activated beta-turn scaffold, 1, with the ability to template a beta-turn conformation within the somatostatin tetrapeptide only upon photolysis. The three-d...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2005.00337.x
更新日期:2006-02-01 00:00:00
abstract::Targeting overexpressed receptors on the cancer cells with radiolabeled peptides has become very important in nuclear oncology in the recent years. Peptides are small and have easy preparation and easy radiolabeling protocol with no side-effect and toxicity. These properties made them a valuable tool for tumor targeti...
journal_title:Chemical biology & drug design
pub_type: 杂志文章,评审
doi:10.1111/cbdd.13413
更新日期:2019-03-01 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::Screening combinatorial libraries of conformationally constrained peptides against macromolecular targets is utilized in identifying novel drug leads and in developing new reagents for chemical biology. In methods such as phage-display selections, biotinylated macromolecular targets are often immobilized on avidin- an...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2006.00401.x
更新日期:2006-07-01 00:00:00
abstract::Ligand- and target structure-based methods are widely used in virtual screening, but there is currently no methodology available that fully integrates these different approaches. Herein, we provide an overview of various attempts that have been made to combine ligand- and structure-based computational screening method...
journal_title:Chemical biology & drug design
pub_type: 杂志文章,评审
doi:10.1111/j.1747-0285.2010.01007.x
更新日期:2010-09-01 00:00:00
abstract::The present study describes ligand-based pharmacophore modeling of a series of structurally diverse acyl coenzyme A cholesterol acyltransferase inhibitors. Quantitative pharmacophore models were generated using HypoGen module of Discovery Studio 2.1, whereby the best pharmacophore model possessing two hydrophobic, one...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2012.01384.x
更新日期:2012-07-01 00:00:00
abstract::An efficient direct aldol reaction has been developed for the synthesis of chiral beta-hydroxy ketone using a combination of C(1)-symmetric chiral prolinamides based on o-phenylenediamine and zinc triflate as catalyst. The reaction was convenient to carry out in aqueous media with up to 98% chemical yields and up to 9...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2010.00998.x
更新日期:2010-08-01 00:00:00
abstract::Physicochemical n-Grams Tool (PnGT) is an open-source standalone software for calculating physicochemical descriptors of protein. PnGT was developed using the Python scripting language and developed the user interface using Tkinter. The software currently calculates 33 physicochemical descriptors along with the sequen...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.13617
更新日期:2020-01-01 00:00:00
abstract::A new propeller-like small molecule was synthesized with three terminal amino side groups. The molecule was found to be a selective nucleic acid binder towards telo21 G-quadruplex DNA compared with other representative nucleic acids including single-stranded DNA (dA21), duplex DNA (ds26) and RNA. The fluorescent signa...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.13394
更新日期:2019-06-01 00:00:00
abstract::Two series of [1,2,4]triazolo[3,4-a]phthalazine and tetrazolo[5,1-a]phthalazine derivatives bearing substituted benzylpiperazine moieties have been synthesized and evaluated for their positive inotropic activity by measuring left atrium stroke volume on isolated rabbit heart preparations. The majority of the derivativ...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12101
更新日期:2013-05-01 00:00:00
abstract::EGFR is a well-established therapeutic target of clinical relevance in cancer. However, acquisition of secondary mutation (T790M) makes first-generation inhibitors ineffective. Therefore, to circumvent the problem of resistance, new T790M/L858R (TMLR) double mutant inhibitors are required. In this study, fragment-base...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.13505
更新日期:2019-07-01 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::Bis-indole derivatives including 1,1-bis(3'-indolyl)-1-(4-chlorophenyl)methane (DIM-C-pPhCl) and substituted quinolines such as chloroquine (CQ) and amodiaquine (AQ) are nuclear receptor 4A2 (NR4A2, Nurr1) ligands, and they exhibit anti-inflammatory activities in mouse and rat models of Parkinson's disease, respective...
journal_title:Chemical biology & drug design
pub_type: 杂志文章,评审
doi:10.1111/cbdd.13564
更新日期:2019-10-01 00:00:00
abstract::In the past decade, the discovery, synthesis, and evaluation for hundreds of CD38 covalent and non-covalent inhibitors has been reported sequentially by our group and partners; however, a systematic structure-based guidance is still lacking for rational design of CD38 inhibitor. Here, we carried out a comparative anal...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12606
更新日期:2015-12-01 00:00:00
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::Tubulin inhibition represents an established target in the field of anticancer research, and over the last 20 years, an intensive search for new antimicrotubule agents has occurred. Indeed, in silico models have been presented that might aid the discovery of novel agents. Among these, a 7-point pharmacophore model has...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2011.01245.x
更新日期:2011-12-01 00:00:00
abstract::Non-secosteroidal ligands are well-known vitamin D receptor (VDR) agonists. In this study, we described a combined QM/MM to define the protein-ligand interaction energy a strong positive correlation in both QM-MM interaction energy and binding free energy against the biological activity. The molecular dynamics simulat...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12754
更新日期:2016-08-01 00:00:00
abstract::Novel series of 3-O-arylalkylbenzamide and 3-O-arylalkyl-2,6-difluorobenzamide derivatives were synthesized and evaluated for their on-target activity and antibacterial activity. The results indicated that the 3-O-arylalkyl-2,6-difluorobenzamide derivatives possessed much better on-target activity and antibacterial ac...
journal_title:Chemical biology & drug design
pub_type: 信件
doi:10.1111/cbdd.12658
更新日期:2016-02-01 00:00:00
abstract::Specific assembly of ribonucleoprotein complexes is essential in controlling various cellular functions including gene regulation. Diverse scaffolds containing proteins or nucleic acids could play key roles in stabilizing specific ribonucleoprotein complexes by enhancing protein-protein or RNA-protein interactions. On...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2007.00501.x
更新日期:2007-04-01 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::Viral infections constantly jeopardize the global public health due to lack of effective antiviral therapeutics. Therefore, there is an imperative need to speed up the drug discovery process to identify novel and efficient drug candidates. In this study, we have developed quantitative structure-activity relationship (...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12834
更新日期:2017-01-01 00:00:00
abstract::Malaria, mainly caused by Plasmodium falciparum and Plasmodium vivax, has been a growing cause of morbidity and mortality. P. falciparum is more lethal than is P. vivax, but there is a vital need for effective drugs against both species. Geranylgeranyl diphosphate synthase (GGPPS) is an enzyme involved in the biosynth...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.13170
更新日期:2018-06-01 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::A low-dimensional method, based on the use of multiple fusion-based similarity measures, is described for graphically depicting and characterizing relationships among molecules in compound databases. The measures are used to construct multi-fusion similarity maps that characterize the relationship of a set of 'test' m...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2007.00579.x
更新日期:2007-11-01 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