Aptamer Functionalization of Nanosystems for Glioblastoma Targeting through the Blood-Brain Barrier.


: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.


J Med Chem


Monaco I,Camorani S,Colecchia D,Locatelli E,Calandro P,Oudin A,Niclou S,Arra C,Chiariello M,Cerchia L,Comes Franchini M




Has Abstract


2017-05-25 00:00:00












  • Synthesis and Cytostatic and Antiviral Profiling of Thieno-Fused 7-Deazapurine Ribonucleosides.

    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


    authors: Tichý M,Smoleń S,Tloušt'ová E,Pohl R,Oždian T,Hejtmánková K,Lišková B,Gurská S,Džubák P,Hajdúch M,Hocek M

    更新日期:2017-03-23 00:00:00

  • Structural aspects of isozyme selectivity in the binding of inhibitors to carbonic anhydrases II and IV.

    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


    authors: Kim CY,Whittington DA,Chang JS,Liao J,May JA,Christianson DW

    更新日期:2002-02-14 00:00:00

  • Angiotensin converting enzyme inhibitors: 1,5-benzothiazepine derivatives.

    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


    authors: Slade J,Stanton JL,Ben-David D,Mazzenga GC

    更新日期:1985-10-01 00:00:00

  • Deconstruction of the α4β2 nicotinic acetylcholine receptor positive allosteric modulator desformylflustrabromine.

    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


    authors: German N,Kim JS,Jain A,Dukat M,Pandya A,Ma Y,Weltzin M,Schulte MK,Glennon RA

    更新日期:2011-10-27 00:00:00

  • Hypocholesterolemic activity of synthetic and natural tocotrienols.

    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


    authors: Pearce BC,Parker RA,Deason ME,Qureshi AA,Wright JJ

    更新日期:1992-10-02 00:00:00

  • Inhibitors of acyl-CoA:cholesterol O-acyl transferase (ACAT) as hypocholesterolemic agents. 8. Incorporation of amide or amine functionalities into a series of disubstituted ureas and carbamates. Effects on ACAT inhibition in vitro and efficacy in vivo.

    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


    authors: O'Brien PM,Sliskovic DR,Blankley CJ,Roth BD,Wilson MW,Hamelehle KL,Krause BR,Stanfield RL

    更新日期:1994-06-10 00:00:00

  • Quick assembly of 1,4-diphenyltriazoles as probes targeting beta-amyloid aggregates in Alzheimer's disease.

    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


    authors: Qu W,Kung MP,Hou C,Oya S,Kung HF

    更新日期:2007-07-12 00:00:00

  • Property- and structure-guided discovery of a tetrahydroindazole series of interleukin-2 inducible T-cell kinase inhibitors.

    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


    authors: Burch JD,Lau K,Barker JJ,Brookfield F,Chen Y,Chen Y,Eigenbrot C,Ellebrandt C,Ismaili MH,Johnson A,Kordt D,MacKinnon CH,McEwan PA,Ortwine DF,Stein DB,Wang X,Winkler D,Yuen PW,Zhang Y,Zarrin AA,Pei Z

    更新日期:2014-07-10 00:00:00

  • Identification of clinically viable quinolinol inhibitors of botulinum neurotoxin A light chain.

    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


    authors: Caglič D,Krutein MC,Bompiani KM,Barlow DJ,Benoni G,Pelletier JC,Reitz AB,Lairson LL,Houseknecht KL,Smith GR,Dickerson TJ

    更新日期:2014-02-13 00:00:00

  • Nonsymmetrical bipiperidyls as inhibitors of vesicular acetylcholine storage.

    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


    authors: Efange SM,Khare A,Parsons SM,Bau R,Metzenthin T

    更新日期:1993-04-16 00:00:00

  • Novel peptidomimetics containing a vinyl ester moiety as highly potent and selective falcipain-2 inhibitors.

    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


    authors: Ettari R,Micale N,Schirmeister T,Gelhaus C,Leippe M,Nizi E,Di Francesco ME,Grasso S,Zappalà M

    更新日期:2009-04-09 00:00:00

  • Synthesis and antihypertensive activity of 3-[(substituted-carbonyl)amino]-2H-1-benzopyrans.

    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


    authors: Cassidy F,Evans JM,Hadley MS,Haladij AH,Leach PE,Stemp G

    更新日期:1992-05-01 00:00:00

  • Synthesis and biological evaluation of analogues of 7-chloro-4,5-dihydro-4- oxo-8-(1,2,4-triazol-4-yl)-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylic acid (TQX-173) as novel selective AMPA receptor antagonists.

    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


    authors: Catarzi D,Colotta V,Varano F,Calabri FR,Filacchioni G,Galli A,Costagli C,Carlà V

    更新日期:2004-01-01 00:00:00

  • Nucleic acid related compounds. 65. New syntheses of 1-(beta-D-arabinofuranosyl)-5(E)-(2-iodovinyl)uracil (IVAraU) from vinylsilane precursors. Radioiodine uptake as a marker for thymidine kinase positive herpes viral infections.

    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


    authors: Robins MJ,Manfredini S,Wood SG,Wanklin RJ,Rennie BA,Sacks SL

    更新日期:1991-07-01 00:00:00

  • Structure-activity relationships of an antimicrobial peptide plantaricin s from two-peptide class IIb bacteriocins.

    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


    authors: Soliman W,Wang L,Bhattacharjee S,Kaur K

    更新日期:2011-04-14 00:00:00

  • Synthesis of potent cyclic hexapeptide NK-1 antagonists. Use of a minilibrary in transforming a peptidal somatostatin receptor ligand into an NK-1 receptor ligand via a polyvalent peptidomimetic.

    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


    authors: Hirschmann R,Yao W,Cascieri MA,Strader CD,Maechler L,Cichy-Knight MA,Hynes J Jr,van Rijn RD,Sprengeler PA,Smith AB 3rd

    更新日期:1996-06-21 00:00:00

  • Alkenylidene bisphenols, a new class of bisphenol bactericide.

    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


    authors: Conradi RA,Vander Wyk JC,Bowlus SB

    更新日期:1979-08-01 00:00:00

  • Synthesis and in vitro photodynamic activity of oligomeric ethylene glycol-quinoline substituted zinc(II) phthalocyanine derivatives.

    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


    authors: Jia X,Yang FF,Li J,Liu JY,Xue JP

    更新日期:2013-07-25 00:00:00

  • Synthesis, biological evaluation, and three-dimensional quantitative structure-activity relationship study of small-molecule positive modulators of adrenomedullin.

    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


    authors: García MA,Martín-Santamaría S,Cacho M,de la Llave FM,Julián M,Martínez A,de Pascual-Teresa B,Ramos A

    更新日期:2005-06-16 00:00:00

  • Discovery of a series of imidazo[4,5-b]pyridines with dual activity at angiotensin II type 1 receptor and peroxisome proliferator-activated receptor-γ.

    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


    authors: Casimiro-Garcia A,Filzen GF,Flynn D,Bigge CF,Chen J,Davis JA,Dudley DA,Edmunds JJ,Esmaeil N,Geyer A,Heemstra RJ,Jalaie M,Ohren JF,Ostroski R,Ellis T,Schaum RP,Stoner C

    更新日期:2011-06-23 00:00:00

  • The first sphingosine 1-phosphate lyase inhibitors against multiple sclerosis: a successful drug discovery tale.

    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


    authors: Cosconati S,Novellino E

    更新日期:2014-06-26 00:00:00

  • Pharmacological Characterization of Low-to-Moderate Affinity Opioid Receptor Agonists and Brain Imaging with 18F-Labeled Derivatives in Rats.

    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


    authors: Ott J,Spilhaug MM,Maschauer S,Rafique W,Jakobsson JE,Hartvig K,Hübner H,Gmeiner P,Prante O,Riss PJ

    更新日期:2020-09-10 00:00:00

  • Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer Chemotherapy.

    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


    authors: Huddle BC,Grimley E,Buchman CD,Chtcherbinine M,Debnath B,Mehta P,Yang K,Morgan CA,Li S,Felton J,Sun D,Mehta G,Neamati N,Buckanovich RJ,Hurley TD,Larsen SD

    更新日期:2018-10-11 00:00:00

  • Isolation, Structural Identification, Synthesis, and Pharmacological Profiling of 1,2-trans-Dihydro-1,2-diol Metabolites of the Utrophin Modulator Ezutromid.

    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


    authors: Chatzopoulou M,Claridge TDW,Davies KE,Davies SG,Elsey DJ,Emer E,Fletcher AM,Harriman S,Robinson N,Rowley JA,Russell AJ,Tinsley JM,Weaver R,Wilkinson IVL,Willis NJ,Wilson FX,Wynne GM

    更新日期:2020-03-12 00:00:00

  • Design, synthesis, and dopamine receptor modulating activity of spiro bicyclic peptidomimetics of L-prolyl-L-leucyl-glycinamide.

    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


    authors: Khalil EM,Ojala WH,Pradhan A,Nair VD,Gleason WB,Mishra RK,Johnson RL

    更新日期:1999-02-25 00:00:00

  • Bicyclic Helical Peptides as Dual Inhibitors Selective for Bcl2A1 and Mcl-1 Proteins.

    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


    authors: D de Araujo A,Lim J,Wu KC,Xiang Y,Good AC,Skerlj R,Fairlie DP

    更新日期:2018-04-12 00:00:00

  • (3-Amino-2-oxoalkyl)phosphonic acids and their analogues as novel inhibitors of D-alanine:D-alanine ligase.

    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


    authors: Chakravarty PK,Greenlee WJ,Parsons WH,Patchett AA,Combs P,Roth A,Busch RD,Mellin TN

    更新日期:1989-08-01 00:00:00

  • Design, synthesis, and biological evaluation of novel disubstituted dibenzosuberones as highly potent and selective inhibitors of p38 mitogen activated protein kinase.

    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


    authors: Koeberle SC,Fischer S,Schollmeyer D,Schattel V,Grütter C,Rauh D,Laufer SA

    更新日期:2012-06-28 00:00:00

  • Studies on 1,2,3-triazoles. 10. Synthesis and antiallergic properties of 9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazoles and their S-oxides.

    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


    authors: Buckle DR,Rockell CJ,Smith H,Spicer BA

    更新日期:1984-02-01 00:00:00

  • Design and optimization of 20-O-linked camptothecin glycoconjugates as anticancer agents.

    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


    authors: Lerchen HG,Baumgarten J,von dem Bruch K,Lehmann TE,Sperzel M,Kempka G,Fiebig HH

    更新日期:2001-11-22 00:00:00