Abstract:
:Polymeric nanoparticles (PNPs) may efficiently deliver in vivo therapeutics to tumors when conjugated to specific targeting agents. Gint4.T aptamer specifically recognizes platelet-derived growth factor receptor β and can cross the blood-brain barrier (BBB). We synthesized Gint4.T-conjugated PNPs able of high uptake into U87MG glioblastoma (GBM) cells and with astonishing EC50 value (38 pM) when loaded with a PI3K-mTOR inhibitor. We also demonstrated in vivo BBB passage and tumor accumulation in a GBM orthotopic model.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Monaco I,Camorani S,Colecchia D,Locatelli E,Calandro P,Oudin A,Niclou S,Arra C,Chiariello M,Cerchia L,Comes Franchini Mdoi
10.1021/acs.jmedchem.7b00527subject
Has Abstractpub_date
2017-05-25 00:00:00pages
4510-4516issue
10eissn
0022-2623issn
1520-4804journal_volume
60pub_type
杂志文章abstract::Two isomeric series of new thieno-fused 7-deazapurine ribonucleosides (derived from 4-substituted thieno[2',3':4,5]pyrrolo[2,3-d]pyrimidines and thieno[3',2':4,5]pyrrolo[2,3-d]pyrimidines) were synthesized by a sequence involving Negishi coupling of 4,6-dichloropyrimidine with iodothiophenes, nucleophilic azidation, a...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.6b01766
更新日期:2017-03-23 00:00:00
abstract::Carbonic anhydrase inhibitors are effective in lowering intraocular pressure, the primary indication of glaucoma. Human carbonic anhydrase II, and possibly carbonic anhydrase IV (CAII and CAIV, respectively), help regulate fluid secretion into the anterior chamber of the eye. Because inhibitors currently formulated as...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm010163d
更新日期:2002-02-14 00:00:00
abstract::The synthesis of chiral 1,5-benzothiazepines 2a-c, 14a-c, 15c, and 16a prepared from cysteine is described. In vitro inhibition of angiotensin converting enzyme (ACE) is reported for each compound. Compound 2c was the most potent in vitro having an IC50 of 2.95 nM. The ester of 2c, i.e. 14c, was found to inhibit the A...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00148a024
更新日期:1985-10-01 00:00:00
abstract::Desformylflustrabromine (dFBr; 1), perhaps the first selective positive allosteric modulator of α4β2 neuronal nicotinic acetylcholine (nACh) receptors, was deconstructed to determine which structural features contribute to its actions on receptors expressed in Xenopus ooycytes using two-electrode voltage clamp techn...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm200834x
更新日期:2011-10-27 00:00:00
abstract::Tocotrienols are farnesylated benzopyran natural products that exhibit hypocholesterolemic activity in vitro and in vivo. The mechanism of their hypolipidemic action involves posttranscriptional suppression of HMG-CoA reductase by a process distinct from other known inhibitors of cholesterol biosynthesis. An efficient...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00098a002
更新日期:1992-10-02 00:00:00
abstract::A series of disubstituted ureas containing amide or amine groups was prepared and evaluated for their ability to inhibit acyl-CoA:cholesterol O-acyl transferase in vitro and to lower plasma total cholesterol in a variety of cholesterol-fed rat models in vivo. The presence of polar or ionizable functionalities within t...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00038a010
更新日期:1994-06-10 00:00:00
abstract::Accumulation of beta-amyloid aggregates (Abeta) in the brain is linked to the pathogenesis of Alzheimer's disease (AD). We report a novel approach for producing 1,4-diphenyltriazoles as probes for targeting Abeta aggregates in the brain. The imaging probes, a series of substituted tricyclic 1,4-diphenyltriazoles showi...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm070467l
更新日期:2007-07-12 00:00:00
abstract::Interleukin-2 inducible T-cell kinase (ITK), a member of the Tec family of tyrosine kinases, plays a major role in T-cell signaling downstream of the T-cell receptor (TCR), and considerable efforts have been directed toward discovery of ITK-selective inhibitors as potential treatments of inflammatory disorders such as...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm500550e
更新日期:2014-07-10 00:00:00
abstract::Botulinum neurotoxins (BoNT) are the most potent toxins known and a significant bioterrorist threat. Few small molecule compounds have been identified that are active in cell-based or animal models, potentially due to toxin enzyme plasticity. Here we screened commercially available quinolinols, as well as synthesized ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm4012164
更新日期:2014-02-13 00:00:00
abstract::Introduction of a nitrogen atom into the cyclohexane ring of 2-(4-phenylpiperidinyl)cyclohexanol (vesamicol, AH5183) yielded two positional isomers, 5-azavesamicol (5, prezamicol) and 4-azavesamicol (6, trozamicol). As inhibitors of vesicular acetylcholine transport, 5 and 6 were found to be 147 and 85 times less pote...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00060a005
更新日期:1993-04-16 00:00:00
abstract::This paper describes the synthesis and biological evaluation of a new class of peptidomimetic falcipain-2 inhibitors based on a 1,4-benzodiazepine scaffold combined with various alpha,beta-unsaturated electrophilic functions such as vinyl-ketone, -amide, -ester, and -nitrile. The profile of reactivity of this class of...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm900047j
更新日期:2009-04-09 00:00:00
abstract::The synthesis and antihypertensive activity of a series of novel 3-[(substituted-carbonyl)amino]-2H-1-benzopyran-4-ols, administered orally to spontaneously hypertensive rats, are described. Optimum activity in this series was observed for compounds with branched alkyl or branched alkylamino groups flanking the carbon...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00087a018
更新日期:1992-05-01 00:00:00
abstract::In recent papers (Catarzi, D.; et al. J. Med. Chem. 2000, 43, 3824-3826; 2001, 44, 3157-3165) we reported chemical and biological studies on 4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates (TQXs) bearing different nitrogen-containing heterocycles at position-8. In particular, from these studies it em...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm030906q
更新日期:2004-01-01 00:00:00
abstract::(Trimethylsilyl)acetylene was coupled with 1-(2,3,5-tri-O-acetyl-beta-D- arabinofuranosyl)-5-iodouracil to give 1- (2,3,5-tri-O-acetyl-beta-D-arabinofuranosyl)-5-[2-(trimethylsilyl)eth yny l] uracil. Lindlar hydrogenation of 4 gave 1-(2,3,4-tri-O-acetyl-beta-D-arabinofuranosyl)-5(Z)-[2- (trimethylsilyl)vinyl]uracil. T...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00111a050
更新日期:1991-07-01 00:00:00
abstract::Class IIb bacteriocins are ribosomally synthesized antimicrobial peptides comprising two different peptides synergistically acting in equal amounts for optimal potency. In this study, we demonstrate for the first time potent (nanomolar) antimicrobial activity of a representative class IIb bacteriocin, plantaricin S (P...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm101540e
更新日期:2011-04-14 00:00:00
abstract::The endogenous peptides somatostatin (SRIF) and substance P comprise very different structures. Although both bind G-protein-coupled receptors, the SRIF receptors (SSTR 1-5) recognize SRIF and related peptides which retain its beta-turn such as the potent cyclic hexapeptide SRIF agonist L-363,301 (6a), but not substan...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm960281e
更新日期:1996-06-21 00:00:00
abstract::Alkenylidene bisphenols are prepared by condensation of an appropriate phenol with a haloacetaldehyde, followed by base-induced elimination, or by condensation of the corresponding aryl methyl ether, elimination, and deprotection of the phenol with boron tribromide. The resulting compounds may be further elaborated by...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00194a022
更新日期:1979-08-01 00:00:00
abstract::A new series of zinc(II) phthalocyanine derivatives have been synthesized and characterized. These macrocycles exhibited a sharp absorption band in the red visible region in DMF, which indicated that they were dissolved well and almost did not aggregate in this solvent. Compared with the unsubstituted zinc(II) phthalo...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm400722d
更新日期:2013-07-25 00:00:00
abstract::Adrenomedullin (AM) is a peptide hormone implicated in blood pressure regulation and in the pathophysiology of several diseases such as hypertension, cancer, diabetes, and renal disorders, becoming an interesting new target for the development of drugs. In a recent high-throughput screening study, a positive modulator...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm050021+
更新日期:2005-06-16 00:00:00
abstract::Mining of an in-house collection of angiotensin II type 1 receptor antagonists to identify compounds with activity at the peroxisome proliferator-activated receptor-γ (PPARγ) revealed a new series of imidazo[4,5-b]pyridines 2 possessing activity at these two receptors. Early availability of the crystal structure of th...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm200409s
更新日期:2011-06-23 00:00:00
abstract::Modulation of sphingosine 1-phosphate (S1P) signaling represents a solid opportunity for multiple sclerosis (MS) treatment. In this issue, a team at Novartis reports on the identification of the first direct S1P lyase (S1PL) inhibitors as new MS agents. One of the most potent inhibitors reported in their work was demo...
journal_title:Journal of medicinal chemistry
pub_type: 评论,杂志文章
doi:10.1021/jm500845y
更新日期:2014-06-26 00:00:00
abstract::The 3,4-dichloro-N-(1-(dimethylamino)cyclohexyl)methyl benzamide scaffold was studied as a template for 18F-positron emission tomography (18F-PET) radiotracer development emphasizing sensitivity to changes in opioid receptor (OR) occupancy over high affinity. Agonist potency, binding affinity, and relevant pharmacolog...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.0c00683
更新日期:2020-09-10 00:00:00
abstract::Aldehyde dehydrogenase (ALDH) activity is commonly used as a marker to identify cancer stem-like cells. The three ALDH1A isoforms have all been individually implicated in cancer stem-like cells and in chemoresistance; however, which isoform is preferentially expressed varies between cell lines. We sought to explore th...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.8b00930
更新日期:2018-10-11 00:00:00
abstract::5-(Ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole (ezutromid, 1) is a first-in-class utrophin modulator that has been evaluated in a phase 2 clinical study for the treatment of Duchenne muscular dystrophy (DMD). Ezutromid was found to undergo hepatic oxidation of its 2-naphthyl substituent to produce two regioisome...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.9b01547
更新日期:2020-03-12 00:00:00
abstract::In the present study, the synthesis of the 5.5.6. and 5.6.5. spiro bicyclic lactam PLG peptidomimetics, compounds 3 and 4, respectively, was undertaken. These peptidomimetics were designed to examine the following: (1) the effect that changing the size of the thiazolidine and lactam ring systems would have on the abil...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm980525q
更新日期:1999-02-25 00:00:00
abstract::A 26-residue peptide BimBH3 binds indiscriminately to multiple oncogenic Bcl2 proteins that regulate apoptosis of cancer cells. Specific inhibition of the BimBH3-Bcl2A1 protein-protein interaction was obtained in vitro and in cancer cells by shortening the peptide to 14 residues, inserting two cyclization constraints ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.8b00010
更新日期:2018-04-12 00:00:00
abstract::The dipeptide D-alanyl-D-alanine is an essential precursor of bacterial peptidoglycan; thus, blocking its formation is a possible target for the design of novel antibacterial agents. The synthesis of this dipeptide by bacterial D-alanine:D-alanine ligase requires ATP. In analogy with glutamine synthetase, we hypothesi...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00128a033
更新日期:1989-08-01 00:00:00
abstract::Synthesis, biological testing, structure-activity relationships (SARs), and selectivity of novel disubstituted dibenzosuberone derivatives as p38 MAP kinase inhibitors are described. Hydrophilic moieties were introduced at the 7-, 8-, and 9-position of the 2-phenylamino-dibenzosuberones, improving physicochemical prop...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm300327h
更新日期:2012-06-28 00:00:00
abstract::Selected derivatives of 9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazole, a new heterocyclic ring system, and their S-oxides have been prepared and evaluated for antiallergic activity in the rat passive cutaneous anaphylaxis screen. Several of the compounds show intravenous potencies similar to or greater than that o...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00368a021
更新日期:1984-02-01 00:00:00
abstract::To improve the biological profile of 20(S)-camptothecin, a novel class of 20-O-linked camptothecin glycoconjugates has been designed for preferential cellular uptake into tumor cells by an active transport mechanism. Such conjugates have been optimized for enhanced solubility, stabilization of the camptothecin lactone...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm010893l
更新日期:2001-11-22 00:00:00