Abstract：
:Alternative splicing of the androgen receptor (AR) is frequently observed in castration resistant prostate cancer (CRPC). One AR isoform, the AR-V7 splice variant, is a constitutively active transcription factor which lacks a ligand binding domain and is therefore undruggable. AR-V7 expression correlates with resistance to androgen receptor signaling inhibitors (ARSi) and poor clinical prognoses. The occurrence of the AR-V7 splice variant is driven by alternative splicing of AR pre-mRNA by the spliceosome, however the mechanistic details are poorly understood. We demonstrate that the splicing factor RBM39 is critical for alternative splicing of the AR-V7 splice variant mRNA transcripts from AR pre-mRNA, and that the anti-cancer drug, indisulam, reduces AR-V7 mRNA levels by degrading RBM39. We report that indisulam effectively reduces AR-V7 in in vitro and in vivo models.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Melnyk JE,Steri V,Nguyen HG,Hann B,Feng FY,Shokat KMdoi
10.1016/j.bmc.2020.115712subject
Has Abstractpub_date
2020-10-15 00:00:00pages
115712issue
20eissn
0968-0896issn
1464-3391pii
S0968-0896(20)30542-3journal_volume
28pub_type
杂志文章abstract：:A series of trans-2-aryl-cyclopropylamine derived compounds were synthesized and evaluated their biological activities against DPP-IV. The structure-activity relationships (SAR) led to the discovery of novel series of DPP-IV inhibitors, having IC(50) values of <100 nM with excellent selectivity over the closely relate...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2009.02.020
更新日期：2009-03-15 00:00:00
abstract：:A new bis-pyrene-labeled oligonucleotide probe (BP-probe) has been designed for the detection of a single base mismatch in single strand (ss) DNA as a target. The sequence of BP-probe was chosen to form stem-loop structure similar to a molecular beacon (MB-probe), yielding bis-pyrene-labeled molecular beacon (BP-MB-pr...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.04.053
更新日期：2008-01-01 00:00:00
abstract：:A series of arylidene N-alkoxydiketopiperazines was designed and stereoselectively synthesized via oxime-ether formation and intramolecular acylation. Possible cyclization and acid-catalyzed rearrangement-fragmentation mechanisms were discussed. The crystal structure of the novel diketopiperazine further confirmed the...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2016.08.038
更新日期：2016-11-01 00:00:00
abstract：:Analogs of the antibiotic fosmidomycin, an inhibitor of the methylerythritol phosphate pathway to isoprenoids, were synthesized and evaluated against the recombinant Synechocystis sp. PCC6803 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR). Fosfoxacin, the phosphate analog of fosmidomycin, and its acetyl congene...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.11.012
更新日期：2006-04-01 00:00:00
abstract：:5-HT(7) receptor antagonists generated antidepressant-like effects in animal model and the involvement of the 5-HT(7) receptor in other pathophysiological mechanisms such as thermoregulation, learning and memory, and sleep has been highlighted by various studies. As one of our efforts to discover a new type of 5-HT(7)...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.11.049
更新日期：2008-03-01 00:00:00
abstract：:A quantitative structure-activity relationship (QSAR) study has been made on two different series of tetrahydropyrimidinones acting as HIV-1 protease inhibitors. A structural parameter, the first order valence molecular connectivity index ((1)chi(v)), has been used to account for the variation in the activity. The pro...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(01)00210-3
更新日期：2001-11-01 00:00:00
abstract：:A QSAR methodology that involves multilinear (Hansch-type) and nonlinear (ANN backpropagation) approaches was developed to correlate the antiplatelet activity of 60 benzoxazinone derivatives against factor Xa. The statistical characteristics provided by multilinear model (R2 = 0.821) indicated satisfactory stability a...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.07.022
更新日期：2006-11-15 00:00:00
abstract：:To detect γ-Glutamyl Transpeptidase (GGT) activity in vitro and in vivo, a bioluminescence probe with high sensitivity and specificity was well designed and synthesized. This probe can be recognized by GGT and release strong bioluminescence with its further reaction with luciferase. The performance of this probe was d...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2017.11.025
更新日期：2018-01-01 00:00:00
abstract：:Based on the spirotryprostatin-A structure, we designed, synthesized, and evaluated different series of compounds belonging to the diketopiperazine structural class as potential cell cycle modulators and cytotoxic agents. Starting from the spirooxoindolthiazolidine scaffold, amide coupling with Pro derivatives and int...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2010.04.079
更新日期：2010-06-15 00:00:00
abstract：:Molecular combinations of two antioxidants (i.e., ascorbic acid and the pharmacophore of alpha-tocopherol), namely the 2,3-dihydroxy-2,3-enono-1,4-lactone and the chromane residues, have been designed and tested for their radical scavenging activities. When evaluated for their capability to inhibit malondialdehyde (MD...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(00)00205-4
更新日期：2000-12-01 00:00:00
abstract：:We have previously reported the discovery and initial SAR of the [1,7]naphthyridine-3-carbonitriles and quinoline-3-carbonitriles as Tumor Progression Loci-2 (Tpl2) kinase inhibitors. In this paper, we report new SAR efforts which have led to the identification of 4-alkylamino-[1,7]naphthyridine-3-carbonitriles. These...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.06.054
更新日期：2007-10-01 00:00:00
abstract：:Two types of structural variants of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] were prepared by a chemoenzymatic route. These 6-O-substituted analogues retained the biological activity of Ins(1,4,5)P3, and were able to elicit Ca2+ release from porcine brain microsomes. Moreover, these derivatives allowed the pr...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(00)82196-3
更新日期：1994-01-01 00:00:00
abstract：:Carbonic anhydrases (CAs) catalyze the reversible hydration of carbon dioxide to bicarbonate and are abundantly distributed in prokaryotes and eukaryotes. There are five classes (α,β,γ,δ,ζ) with no significant sequence or structural identity among them, a remarkable example of convergent evolution. The β and γ classes...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.12.005
更新日期：2013-03-15 00:00:00
abstract：:The binding stoichiometry, binding constants, and inclusion mode of some water-soluble negatively charged cyclodextrin derivatives, i.e. heptakis-[6-deoxy-6-(3-sulfanylpropanoic acid)]-β-cyclodextrin(H1), heptakis-[6-deoxy-6-(2-sulfanylacetic acid)]-β-cyclodextrin(H2), mono-[6-deoxy-6-(3-sulfanylpropanoic acid)]-β-cyc...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2018.03.013
更新日期：2018-05-15 00:00:00
abstract：:Hetero-Diels-Alder reactions of 1,3-bis(silyloxy)-1,3-butadienes with arylsulfonylcyanides afforded a variety of 4-hydroxy-2-(arylsulfonyl)pyridines. Several derivatives show antimicrobial activity against Gram-positive bacteria. ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.10.033
更新日期：2008-12-01 00:00:00
abstract：OBJECTIVE:A new family of 3'-(Mono, di or tri-substituted phenyl)-4'-(4-(methylsulfonyl) phenyl) spiroisoxazoline derivatives containing indanone spirobridge was designed, synthesized, and evaluated for their selective COX-2 inhibitory potency and cytotoxicity on different cell lines. METHODS:A synthetic reaction base...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2020.115960
更新日期：2021-01-02 00:00:00
abstract：:The toxicity of the molecules currently used in the treatment of human cytomegalovirus (HCMV) in immunocompromised hosts often causes interruption of the therapy. Cyclodextrins (Cds), oligosaccharides possessing a hydrophobic cavity, have the property of forming inclusion complexes with a great number of molecules, im...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(00)00247-9
更新日期：2001-02-01 00:00:00
abstract：:Structural features and hydrogen-bond interactions of dinotefuran (DIN), imidacoloprid (IMI) and acetamiprid (ACE) have been investigated experimentally through analyses of new crystal structures and observations in structural databases, as well as by Density Functional Theory quantum chemical calculations. Several co...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2011.10.019
更新日期：2011-12-15 00:00:00
abstract：:A versatile parallel synthetic method to obtain three series of non-cyclic analogues of the first drug-like selective angiotensin II AT(2) receptor agonist (1) has been developed. In analogy with the transformation of losartan to valsartan it was demonstrated that a non-cyclic moiety could be employed as an imidazole ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.07.026
更新日期：2007-11-15 00:00:00
abstract：:S-Nitrosoglutathione (GSNO) relaxes vascular smooth muscles, prevents platelet aggregation, and acts as a potential in vivo nitric oxide donor. 3-Nitroso-1,3-thiazolidine-4-thiocarboxamide (1), a N-nitrosothio-proline analogue, exhibited a high GSNO formation activity. In this study, two compounds (2 and 3) based on c...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2015.09.008
更新日期：2015-10-15 00:00:00
abstract：:Inhibition of the endonuclease activity of influenza RNA-dependent RNA polymerase is recognized as an attractive target for the development of new agents for the treatment of influenza infection. Our earlier study employing small molecule fragment screening using a high-resolution crystal form of pandemic 2009 H1N1 in...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.08.053
更新日期：2013-11-01 00:00:00
abstract：:A range of N-phenethyl, N-phenacyl, and N-(1- and 2-naphthylmethyl) derivatives of 5,7-dibromoisatin 2 were prepared by N-alkylation reactions. Their activity against human monocyte-like histiocytic lymphoma (U937), leukemia (Jurkat), and breast carcinoma (MDA-MB-231) cell lines was assessed. The results allowed furth...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.12.026
更新日期：2008-03-15 00:00:00
abstract：:Inhibition of receptor tyrosine kinases (RTKs) continued to be a successful approach for the treatment of many types of human cancers and many potent small molecules kinase inhibitors have been discovered the last decade. In the present study, we describe the synthesis of thienopyrimidine derivatives and their pharmac...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2015.10.035
更新日期：2015-11-15 00:00:00
abstract：:The present study was designed to synthesize and evaluate pyrrolo-isoxazole benzoic acid derivatives as potential acetylcholinesterase (AChE) inhibitors for the management of Alzheimer's disease. The synthesis of pyrrolo-isoxazole benzoic acid derivatives involved ring opening cyclization of p-aminobenzoic acid with m...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2011.05.027
更新日期：2012-01-01 00:00:00
abstract：:Two new daphne diterpene esters Yuanhuajine (2) and Yuanhuagine (4), together with three known daphne diterpene esters yuanhuacine (1), yuanhuadine (3), and yuanhuapine (5), were isolated and identified from Daphne genkwa, a traditional Chinese medicine. Their structures were elucidated by a combination of UV, IR, MS ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.01.055
更新日期：2006-06-01 00:00:00
abstract：:The donor-acceptor interaction between a tertiary amine and an aldehyde, first observed among a select class of alkaloids, was deliberately established in a peptidomimetic (1a-c) to mimic features of the two principal transition states of peptide hydrolysis. Compounds 1a-c show preferential adoption in methanol and wa...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.01.031
更新日期：2006-06-01 00:00:00
abstract：:Synthesis of new 6-ureido-4-anilinoquinazolines have been accomplished and their in vitro antimalarial activity against chloroquine-sensitive P. falciparum have been examined. Out of 64 compounds evaluated, the IC(50) of 16 compounds which have displayed MIC of 0.25 microg/mL were also recorded. One of the compounds (...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.11.005
更新日期：2009-01-01 00:00:00
abstract：:omega-(1H-Imidazol-4-yl)alkane-1-sulfonamides were prepared and found to be potent histamine H(3) receptor antagonists. High receptor affinity and a low difference in the data between the bioassays were achieved with 5-(1H-imidazol-4-yl)pentane-1-sulfonic acid 4-chlorobenzylamide (16). Good in vitro profiles were also...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(01)00295-4
更新日期：2002-02-01 00:00:00
abstract：:A small molecule library of pyrido[2,3-d]pyrimidine-2,4-dione derivatives 6-16 was synthesized from 6-amino-1,3-disubstituted uracils 18, characterized, and screened for inhibitory activity against eukaryotic elongation factor-2 kinase (eEF-2K). To understand the binding pocket of eEF-2K, structural modifications of t...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2014.06.050
更新日期：2014-09-01 00:00:00
abstract：:The binding constants (K(i) values) of 24 caracurine V and 6 iso-caracurine V analogues for the muscle type of nicotinic ACh receptors (nAChR) from Torpedo californica were determined in a binding assay using (+/-)-[(3)H]epibatidine as a radioligand. The allyl alcohol group present in the iso-caracurine V ring system ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2004.08.053
更新日期：2004-12-01 00:00:00
