Abstract：
:Double-stranded RNA has become a ubiquitous tool for inhibition of gene expression in the laboratory. If similar success could be achieved in vivo, duplex RNA might provide a new class of therapeutics capable of treating a broad spectrum of disease. Chemists and biologists developing duplex RNA as a drug have made progress but continue to face challenges. This review presents the current status of duplex RNA in the clinic and comments on future prospects for the approach.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Watts JK,Corey DRdoi
10.1016/j.bmcl.2010.03.109subject
Has Abstractpub_date
2010-06-01 00:00:00pages
3203-7issue
11eissn
0960-894Xissn
1464-3405pii
S0960-894X(10)00450-6journal_volume
20pub_type
杂志文章abstract：:Cyclophilins (Cyps) are ubiquitous proteins that effect the cis-trans isomerization of Pro amide bonds, and are thus crucial to protein folding. CypA is the most prevalent of the ~19 human Cyps, and plays a crucial role in viral infectivity, most notably for HIV-1 and HCV. Cyclophilins have been shown to play key role...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2013.05.101
更新日期：2013-08-15 00:00:00
abstract：:A new family of bioactive bromotyrosine derivatives, termed mololipids, was recently isolated from a Hawaiian sponge, but could not be resolved into individual components by chromatography. To complete their structural characterization and better understand structure-activity relationships, the first pure samples of d...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(00)00543-6
更新日期：2000-12-04 00:00:00
abstract：:We report the design, synthesis, biological activity and docking studies of series of novel pyrazolo[3,4-d]pyrimidinones as DPP-IV inhibitors in diabetes. Molecules were synthesized and evaluated for their DPP-IV inhibition activity. Compounds 5e, 5k, 5o and 6a were found to be potent inhibitors of DPP-IV enzyme. Amon...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2015.09.015
更新日期：2015-10-15 00:00:00
abstract：:The eryA gene of the bacterial pathogen Brucella abortus has been functionally expressed in Escherichia coli. The resultant EryA was shown to catalyze the ATP-dependent conversion of erythritol to L-erythritol-4-phosphate (L-E4P). The steady state kinetic parameters of this reaction were determined and the enzyme was ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(02)01032-6
更新日期：2003-02-24 00:00:00
abstract：:Discovery of a series of tert-butyl pyrrolidine derived, potent and orally bioavailable melanocortin receptor subtype-4 (MC4R) selective modulators is disclosed. ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2008.04.049
更新日期：2008-06-01 00:00:00
abstract：:A series of new peptoids as endothelin receptor antagonists has been synthesized. Screening them for their ability to bind with endothelin receptors (ET(A) and ET(B)) competitively in the presence of (125I) endothelin led to the discovery of compounds as possible leads with IC50s in the low micromolar concentrations. ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(01)00009-9
更新日期：2001-02-26 00:00:00
abstract：:This Letter details our ongoing efforts to develop selective positive allosteric modulators (PAMs) of the mGlu2/4 heterodimeric receptor that exists in the CNS and may represent a novel drug target to modulate the glutamatergic system. As multiple hit-to-lead campaigns from HTS hits failed to produce selective small m...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2020.127212
更新日期：2020-07-01 00:00:00
abstract：:We identified and tested bisphosphonates as inhibitors of a protozoan molecular target. Computational modeling studies demonstrated that these compounds are mimics of the natural substrate of the enzyme. The most potent bisphosphonates in vitro are pamidronate and risedronate, which inhibit the purine transferase from...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2004.06.042
更新日期：2004-09-06 00:00:00
abstract：:Substituted quinoline-2,4-dicarboxylates (QDCs) are conformationally-restricted mimics of glutamate that were previously reported to selectively block the glutamate vesicular transporters (VGLUTs). We find that expanding the QDC scaffold to benzoquinoline dicarboxylic acids (BQDC) and naphthoquinoline dicarboxylic aci...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2013.12.086
更新日期：2014-02-01 00:00:00
abstract：:Amidino-phenoxy quinoline derivatives represent a new class of potent thrombin inhibitors with good selectivity and remarkably low molecular weight (M(W): 335-391). X-ray analyses of thrombin-bound inhibitors revealed that enzyme inhibition is mainly based on hydrophobic interactions. ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(03)00442-6
更新日期：2003-07-21 00:00:00
abstract：:A novel application of distance-based topological indices : Wiener (W)-, Szeged (Sz)-, Padmakar-Ivan (PI)-, and Sadhana (Sd)-indices in modeling electronic absorption bands of arene absorption spectra has been described. It is demonstrated that all these indices correlate linearly with the logarithm of beta and para e...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2004.06.094
更新日期：2004-09-20 00:00:00
abstract：:This communication describes the synthesis and in vitro biological evaluation of novel generation 5 PAMAM dendrimers conjugated with riboflavin as a targeting ligand. Cell-based experiments demonstrated that a dendrimer conjugated with riboflavin is able to undergo cellular binding and uptake in KB cells, and when the...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2010.07.005
更新日期：2010-09-01 00:00:00
abstract：:A series of N6,2-disubstituted adenosine analogues have been synthesized and their functional activity measured against A2a and A1 receptors. Examples of compounds with both a lipophilic N6-substituent and amino-functionalized 2-position were highly active at the A2a receptor on the human neutrophil. ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(00)00017-2
更新日期：2000-02-21 00:00:00
abstract：:Autotaxin (ATX) is an attractive target for the anticancer therapeutics that inhibits angiogenesis, invasion and migration. ATX is an extracellular lysophospholipase D that hydrolyzes lysophosphatidylcholine to form the bioactive lipid lysophosphatidic acid. The aromatic phosphonate S32826 was the first described nano...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2011.03.068
更新日期：2011-09-01 00:00:00
abstract：:A series of fluconazole analogues 5-20 incorporating azaindole and indole moieties were prepared using oxirane intermediates synthesized under microwave irradiation. All of the compounds were evaluated in vitro against two clinically important fungi, Candida albicans and Aspergillus fumigatus. Four derivatives 6, 13, ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2007.04.038
更新日期：2007-07-01 00:00:00
abstract：:Cancer cells isolated from two patients with malignant non-Hodgkin B-cell lymphomas that became resistant to chemotherapy during clinical treatment were made ≥fourfold resistant in culture to anticancer drugs, that is cisplatin, etoposide, methotrexate and bortezomib. Because most resistant lines showed significantly ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2012.08.091
更新日期：2012-11-01 00:00:00
abstract：:Breast cancer is the most common malignancy among females, and cancer invasion and metastasis are the leading causes of cancer death in breast cancer patients. Pterostilbene, a naturally occurring dimethylether analogue of resveratrol, has been demonstrated to possess anti-cancer effects. However, inhibitory effects o...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2013.12.115
更新日期：2014-02-15 00:00:00
abstract：:Tubulin is subject to a reversible post-translational modification involving polyglutamylation and deglutamylation of glutamate residues in its C-terminal tail. This process plays key roles in regulating the function of microtubule associated proteins, neuronal development, and metastatic progression. This study descr...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2013.05.069
更新日期：2013-08-01 00:00:00
abstract：:3-Trifluoromethylflavonoid derivatives were prepared for the first time by trifluoromethylation of 3-iodoflavonoid derivatives. Other C ring and B ring trifluoromethylated flavonoid derivatives were also prepared. All the compounds were tested for their effect on the U2OS cell cycle in vitro. Bistrifluoromethylated ap...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2005.07.047
更新日期：2005-10-15 00:00:00
abstract：:Incorporation of a carboxylic acid into a series of uracil derivatives as hGnRH-R antagonists resulted in a significant reduction of CYP3A4 inhibitory activity. Highly potent hGnRH antagonists with low CYP3A4 inhibitory liability, such as 8a and 8d, were identified. Thus, 8a had a K(i) of 2.2 nM at GnRH-R and an IC(50...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2008.04.036
更新日期：2008-06-01 00:00:00
abstract：:We synthesized DL-shikonin, shikonin, alkanin, and their cyclo-derivatives and acyl-derivatives. These compounds have low cytotoxicity, as well as inhibitory activity against the telomerase enzyme, except cyclo-derivatives. ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(02)00158-0
更新日期：2002-05-20 00:00:00
abstract：:Structure-guided design led to the discovery of novel chemical scaffolds for B-Raf inhibitors. Both type I and type II kinase inhibitors have been explored and lead compounds with good potency and excellent selectivity have been identified. ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2011.10.012
更新日期：2011-12-01 00:00:00
abstract：:A series of Incentrom A analogs that inhibit the chromosome segregation process in yeast were synthesized and tested for their effects on chromosome stability and cell proliferation. Pharmacophore and structure-activity relationship of Incentrom A for the anti-yeast activity were established. ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2008.07.006
更新日期：2008-08-15 00:00:00
abstract：:As part of the presented research, thirteen new aminoalkanol derivatives were designed and obtained by chemical synthesis. In vivo studies (mice, i.p.) showed anticonvulsant activity (MES) of nine compounds, and in the case of one compound (R,S-trans-2-((2-(2,3,5-trimethylphenoxy)ethyl)amino)cyclohexan-1-ol, 4) both a...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2020.127325
更新日期：2020-08-15 00:00:00
abstract：:New, non-natural dinucleotide 5'-monophosphates, with a surrogate isonucleoside component of l-related stereochemistry at the 'terminal' position, have been synthesized. Structures of 2a-c were confirmed by multinuclear NMR spectra ((1)H, (13)C, (31)P, COSY), UV hypochromicity and FAB HRMS data. These compounds are to...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2004.07.050
更新日期：2004-10-04 00:00:00
abstract：:Inactivation of the NF-κB signaling pathway by inhibition of IKKβ is a well-known approach to treat inflammatory diseases such as rheumatoid arthritis and cancer. Thienopyrimidine-based analogues were designed through modification of the known IKKβ inhibitor, SPC-839, and then biologically evaluated. The resulting ana...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2014.04.058
更新日期：2014-06-15 00:00:00
abstract：:In order to exploit cyclophilin as a potential target for neurological drug design, we demonstrate in this presentation that several nonimmunosuppressant analogues of cyclosporin A, modified at the various positions in the 'effector' domain, are equipotent nerve growth agents compared to cyclosporin A. Our results sug...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2004.06.028
更新日期：2004-09-06 00:00:00
abstract：:A series of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles was designed and synthesized as anticonvulsant agents. Conformational analysis and superimposition of energy minima conformers of the designed molecules on estazolam, a known benzodiazepine receptor agonist, revealed that the main proposed benzodia...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2005.04.018
更新日期：2005-06-15 00:00:00
abstract：:The discovery and optimization of a novel series of prolinol-derived GHSR agonists is described. This series emerged from a 11,520-member solid-phase library targeting the GPCR protein superfamily, and the rapid optimization of low micromolar hits into single-digit nanomolar leads can be attributed to the solid-phase ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2008.07.120
更新日期：2008-09-15 00:00:00
abstract：:Herein we outline the antibacterial activity of amino acid containing thiazolidinediones and rhodanines against Gram-positive bacteria Staphylococcus aureus ATCC 31890, Staphylococcus epidermidis and Bacillus subtilis ATCC 6633. The rhodanine derivatives were generally more active than the analogous thiazolidinediones...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2012.02.100
更新日期：2012-04-15 00:00:00
