当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Design, synthesis, and biological evaluation of theranostic vitamin-linker-taxoid conjugates.

Design, synthesis, and biological evaluation of theranostic vitamin-linker-taxoid conjugates.

Abstract：

:Novel tumor-targeting theranostic conjugates 1 and 2, bearing either a fluorine-labeled prosthetic as a potential (18)F-PET radiotracer (1) or a fluorescence probe (2) for internalization studies in vitro, were designed and synthesized. We confirmed efficient internalization of 2 in biotin-receptor positive (BR+) cancer cells via receptor-mediated endocytosis (RME) based on flow cytometry and confocal fluorescence microscopy (CFM) analyses, which exhibited very high specificity to BR+ cancer cells. The potency and cancer-cell selectivity of 1 were evaluated against MX-1, L1210FR and ID8 cancer cells (BR+) as well as L1210 cells and WI38 normal human lung fibroblast cells (biotin-receptor negative: BR-). In particular, we designed and performed an assay in the presence of glutathione ethyl ester (GSH-OEt) wherein only 1 molecules internalized into cells via RME in the first 24 h period exert cytotoxic effect. The observed selectivity of 1 was remarkable, with 2 orders of magnitude difference in IC50 values between BR+ cancer cells and WI38 cells, demonstrating a salient feature of this tumor-targeted drug delivery system.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Vineberg JG,Wang T,Zuniga ES,Ojima I

doi

10.1021/jm5019115

subject

Has Abstract

pub_date

2015-03-12 00:00:00

pages

2406-16

issue

5

eissn

0022-2623

issn

1520-4804

journal_volume

58

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Structure-based optimization of protein tyrosine phosphatase 1B inhibitors: from the active site to the second phosphotyrosine binding site.

    abstract：:Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin and leptin receptor pathways and thus an attractive therapeutic target for diabetes and obesity. Starting with a high micromolar lead compound, structure-based optimization of novel PTP1B inhibitors by extension of the molecule from the enz...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0702478

    authors： Wilson DP,Wan ZK,Xu WX,Kirincich SJ,Follows BC,Joseph-McCarthy D,Foreman K,Moretto A,Wu J,Zhu M,Binnun E,Zhang YL,Tam M,Erbe DV,Tobin J,Xu X,Leung L,Shilling A,Tam SY,Mansour TS,Lee J

    更新日期：2007-09-20 00:00:00

  • Computational predictions of binding affinities to dihydrofolate reductase: synthesis and biological evaluation of methotrexate analogues.

    abstract：:The relative binding affinities to human dihydrofolate reductase of four new potential antifolates, containing ester linkages between the two aromatic systems, were estimated by free energy perturbation simulations. The ester analogue, predicted to exhibit the highest binding affinity to human dihydrofolate reductase,...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0009639

    authors： Graffner-Nordberg M,Marelius J,Ohlsson S,Persson A,Swedberg G,Andersson P,Andersson SE,Aqvist J,Hallberg A

    更新日期：2000-10-19 00:00:00

  • C-9 and N-substituted analogs of cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3- propyl-1H-benz[e]indole-9-carboxamide: 5-HT1A receptor agonists with various degrees of metabolic stability.

    abstract：:Closely related analogs of the 5-HT1A receptor agonist cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-propyl-1H-benz[e]indole-9- carboxamide (1, U93385) were synthesized and pharmacologically evaluated. 9-Carboxamide analogs with varied nitrogen substitution (R2) were synthesized, and their serotonergic activity was evaluate...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00004a018

    authors： Haadsma-Svensson SR,Svensson K,Duncan N,Smith MW,Lin CH

    更新日期：1995-02-17 00:00:00

  • (E)-3-(4-Oxo-4H-quinazolin-3-yl)-2-propenoic acids, a new series of antiallergy agents.

    abstract：:A series of substituted (E)-3-(4-oxo-4H-quinazolin-3-yl)-2-propenoic acids was prepared and evaluated in the rat passive cutaneous anaphylaxis (PCA) test for antiallergic activity. Alkoxy, alkylthio, and isopropyl substituents at the 6- or 8-positions provided highly potent compounds. Conversion to the Z isomer, reduc...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00357a018

    authors： LeMahieu RA,Carson M,Nason WC,Parrish DR,Welton AF,Baruth HW,Yaremko B

    更新日期：1983-03-01 00:00:00

  • Structural requirements for inhibition of the neuronal nitric oxide synthase (NOS-I): 3D-QSAR analysis of 4-oxo- and 4-amino-pteridine-based inhibitors.

    abstract：:The family of homodimeric nitric oxide synthases (NOS I-III) catalyzes the generation of the cellular messenger nitric oxide (NO) by oxidation of the substrate L-arginine. The rational design of specific NOS inhibitors is of therapeutic interest in regulating pathological NO levels associated with sepsis, inflammatory...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm020074g

    authors： Matter H,Kotsonis P,Klingler O,Strobel H,Fröhlich LG,Frey A,Pfleiderer W,Schmidt HH

    更新日期：2002-07-04 00:00:00

  • Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening.

    abstract：:A structure-based virtual screening (SBVS) was conducted on a ligand-supported homology model of the human histamine H4 receptor (hH4R). More than 8.7 million 3D structures derived from different vendor databases were investigated by docking to the hH4R binding site using FlexX. A total of 255 selected compounds were ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm7014777

    authors： Kiss R,Kiss B,Könczöl A,Szalai F,Jelinek I,László V,Noszál B,Falus A,Keseru GM

    更新日期：2008-06-12 00:00:00

  • Methyl analogues of the experimental Alzheimer drug phenserine: synthesis and structure/activity relationships for acetyl- and butyrylcholinesterase inhibitory action.

    abstract：:With the goal of developing potential Alzheimer's pharmacotherapeutics, we have synthesized a series of novel analogues of the potent anticholinesterases phenserine (2) and physostigmine (1). These derivatives contain methyl (3, 4, 6), dimethyl (5, 7, 8, 10, 11) and trimethyl (14) substituents in each position of the ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm010080x

    authors： Yu Q,Holloway HW,Flippen-Anderson JL,Hoffman B,Brossi A,Greig NH

    更新日期：2001-11-22 00:00:00

  • Synthesis and antimalarial activity of 2-guanidino-4-oxoimidazoline derivatives.

    abstract：:A series of 2-guanidino-4-oxoimidazoline (deoxo-IZ) derivatives was prepared and showed potent antimalarial activities in rodent and Rhesus models. Compound 8e, the most potent analogues of this series, is the first non-8-aminoqinoline antimalarial that demonstrated radical curative activity in non-human primate by or...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm200111g

    authors： Liu X,Wang X,Li Q,Kozar MP,Melendez V,O'Neil MT,Lin AJ

    更新日期：2011-07-14 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

    doi：10.1021/jm00087a018

    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 structure-activity relationships of potent new angiotensin converting enzyme inhibitors containing saturated bicyclic amino acids.

    abstract：:The synthesis of a series of novel, potent angiotensin converting enzyme (ACE) inhibitors containing saturated bicyclic amino acids in place of proline is described. Octahydroindole-2-carboxylic acid, octahydroisoindole-1-carboxylic acid, and octahydro-3-oxoisoindole-1-carboxylic acid can replace proline in both sulfh...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00389a006

    authors： Blankley CJ,Kaltenbronn JS,DeJohn DE,Werner A,Bennett LR,Bobowski G,Krolls U,Johnson DR,Pearlman WM,Hoefle ML

    更新日期：1987-06-01 00:00:00

  • Syntheses and structure-activity relationships of novel retinoid X receptor agonists.

    abstract：:As part of our studies to develop novel retinoids with increased affinity and selectivity for the retinoid X receptor (RXR) subfamily, we have designed and synthesized a series of (E,E,E)-7-(1,2,3, 4-tetrahydroquinolin-6-yl)-7-alkyl-6-fluoro-3-methylhepta-2, 4, 6-trienoic acid derivatives. These tetrahydroquinolines, ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm980058c

    authors： Hibi S,Kikuchi K,Yoshimura H,Nagai M,Tai K,Hida T

    更新日期：1998-08-13 00:00:00

  • Irreversible enzyme inhibitors. 200. Active-site-directed inhibitors of deoxycytidine kinase.

    abstract：:Forty-three pyrimidine derivatives, mainly containing the 4-aminopyrimidine system, have been prepared and evaluated as inhibitors of deoxycytidine kinase. The most effective inhibitors were 2-alkylthio-4-aminopyrimidines and 1-alky-1-cytosines. The best inhibitors in both groups were those with large alkyl substituen...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00211a018

    authors： Ward AD,Baker BR

    更新日期：1977-01-01 00:00:00

  • Discovery of Hydrolysis-Resistant Isoindoline N-Acyl Amino Acid Analogues that Stimulate Mitochondrial Respiration.

    abstract：:N-Acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. We found that administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure, indicating that this pathway might be useful for treating obesity and associated...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b00029

    authors： Lin H,Long JZ,Roche AM,Svensson KJ,Dou FY,Chang MR,Strutzenberg T,Ruiz C,Cameron MD,Novick SJ,Berdan CA,Louie SM,Nomura DK,Spiegelman BM,Griffin PR,Kamenecka TM

    更新日期：2018-04-12 00:00:00

  • Use of medium-sized cycloalkyl rings to enhance secondary binding: discovery of a new class of human immunodeficiency virus (HIV) protease inhibitors.

    abstract：:A unique strategy for the enhancement of secondary binding of an inhibitor to an enzyme has been demonstrated in the design of new human immunodeficiency virus (HIV) protease inhibitors. When the planar benzene ring of a 4-hydroxycoumarin lead compound (1a, Ki = 0.800 microM) was replaced with medium-sized (i.e., 7-9)...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00011a008

    authors： Romines KR,Watenpaugh KD,Tomich PK,Howe WJ,Morris JK,Lovasz KD,Mulichak AM,Finzel BC,Lynn JC,Horng MM

    更新日期：1995-05-26 00:00:00

  • Nucleoside 5'-monophosphate analogues. Synthesis of 5'-sulfamino-5'-deoxynucleosides.

    abstract：:The synthesis of two new nucleotide analogues is described. 5'-Sulfamino-5'-deoxyadenosine (1) was prepared by reaction of 5'-amino-5'-deoxyadenosine with (CH3)3N.203, and 5'-sulfamino-5'-deoxythymidine (2) was prepared from 5'-amino-5'-deoxythymidine by a similar reaction. The 5'-sulfamino nucleosides are shown to be...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00205a024

    authors： Mungall WS,Lemmen LJ,Lemmen KL,Dethmers JK,Norling LL

    更新日期：1978-07-01 00:00:00

  • Reducing the peptidyl features of caspase-3 inhibitors: a structural analysis.

    abstract：:Caspases are cysteine proteases that specifically cleave Asp-Xxx bonds. They are key agents in inflammation and apoptosis and are attractive targets for therapy against inflammation, neurodegeneration, ischemia, and cancer. Many caspase structures are known, but most involve either peptide or protein inhibitors, unatt...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0305523

    authors： Becker JW,Rotonda J,Soisson SM,Aspiotis R,Bayly C,Francoeur S,Gallant M,Garcia-Calvo M,Giroux A,Grimm E,Han Y,McKay D,Nicholson DW,Peterson E,Renaud J,Roy S,Thornberry N,Zamboni R

    更新日期：2004-05-06 00:00:00

  • Synthesis of prenyl pyrophosphonates as new potent phosphoantigens inducing selective activation of human Vgamma9Vdelta2 T lymphocytes.

    abstract：:Gamma9delta2T cells represent the most abundant population of human blood gammadeltaT lymphocytes. They produce and promote strong cytotoxic activity against many pathogens that are implicated in several human infectious diseases. Their activation requires their exposure to small phosphorus-containing antigens in the ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm049861z

    authors： Zgani I,Menut C,Seman M,Gallois V,Laffont V,Liautard J,Liautard JP,Criton M,Montero JL

    更新日期：2004-08-26 00:00:00

  • Chemoreactive-Inspired Discovery of Influenza A Virus Dual Inhibitor to Block Hemagglutinin-Mediated Adsorption and Membrane Fusion.

    abstract：:Owing to the emergence of drug resistance and high morbidity and mortality, the need for novel anti-influenza A virus (IAV) drugs with divergent targets is highly sought after. Herein, we reveal the discovery of an anti-IAV agent as a dual inhibitor to block hemagglutinin-mediated adsorption and membrane fusion using ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.0c00312

    authors： Wu G,Yu G,Yu Y,Yang S,Duan Z,Wang W,Liu Y,Yu R,Li J,Zhu T,Gu Q,Li D

    更新日期：2020-07-09 00:00:00

  • New series of morpholine and 1,4-oxazepane derivatives as dopamine D4 receptor ligands: synthesis and 3D-QSAR model.

    abstract：:Since the identification of the dopamine D(4) receptor subtype and speculations about its possible involvement in schizophrenia, much work has been put into development of selective D(4) ligands. These selective ligands may be effective antipsychotics without extrapyramidal side effects. This work describes the synthe...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm031111m

    authors： Audouze K,Nielsen EØ,Peters D

    更新日期：2004-06-03 00:00:00

  • Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 Inhibitors) in clinical trials for cancer treatment.

    abstract：:Design of small-molecule inhibitors (MDM2 inhibitors) to block the MDM2-p53 protein-protein interaction has been pursued as a new cancer therapeutic strategy. In recent years, potent, selective, and efficacious MDM2 inhibitors have been successfully obtained and seven such compounds have been advanced into early phase...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1021/jm501092z

    authors： Zhao Y,Aguilar A,Bernard D,Wang S

    更新日期：2015-02-12 00:00:00

  • (1aR,5aR)1a,3,5,5a-Tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid (MK-1903): a potent GPR109a agonist that lowers free fatty acids in humans.

    abstract：:G-protein coupled receptor (GPCR) GPR109a is a molecular target for nicotinic acid and is expressed in adipocytes, spleen, and immune cells. Nicotinic acid has long been used for the treatment of dyslipidemia due to its capacity to positively affect serum lipids to a greater extent than other currently marketed drugs....

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,随机对照试验

    doi：10.1021/jm2010964

    authors： Boatman PD,Lauring B,Schrader TO,Kasem M,Johnson BR,Skinner P,Jung JK,Xu J,Cherrier MC,Webb PJ,Semple G,Sage CR,Knudsen J,Chen R,Luo WL,Caro L,Cote J,Lai E,Wagner J,Taggart AK,Carballo-Jane E,Hammond M,Collett

    更新日期：2012-04-26 00:00:00

  • N7-Substituted 7-aminoactinomycin D analogues. Synthesis and biological properties.

    abstract：:A series of N7-substituted 7-aminoactinomycin D analogues with alkyl, aralkyl, and heteroaralkyl substituents was synthesized and their biological properties were studied. All of these analogues proved to be 22- to 28-fold less toxic than actinomycin D when tested against human lymphoblastic leukemia cells (CCRF-CEM) ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00207a021

    authors： Madhavarao MS,Chaykovsky M,Sengupta SK

    更新日期：1978-09-01 00:00:00

  • Synthesis of steroidal nitrosoureas with antitumor activity.

    abstract：:Four steroidal nitrosoureas with structures which may permit specific binding to estrogen receptor were synthesized. Inhibitory activity was observed against the growth of the DMBA-induced transplantable rat mammary tumor 13762. ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00188a015

    authors： Lam HY,Begleiter A,Goldenberg GJ,Wong CM

    更新日期：1979-02-01 00:00:00

  • Discovery of highly potent and selective inhibitors of neuronal nitric oxide synthase by fragment hopping.

    abstract：:Selective inhibition of neuronal nitric oxide synthase (nNOS) has been shown to prevent brain injury and is important for the treatment of various neurodegenerative disorders. This study shows that not only greater inhibitory potency and isozyme selectivity but more druglike properties can be achieved by fragment hopp...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm801220a

    authors： Ji H,Li H,Martásek P,Roman LJ,Poulos TL,Silverman RB

    更新日期：2009-02-12 00:00:00

  • Potent and selective alpha-ketoheterocycle-based inhibitors of the anandamide and oleamide catabolizing enzyme, fatty acid amide hydrolase.

    abstract：:A study of the structure-activity relationships (SAR) of 2f (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed, targeting the 5-position of the oxazole. Examination of a series of substituted benzene derivatives (12-14) revealed that the optimal position for substitution was the meta-positi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0611509

    authors： Romero FA,Du W,Hwang I,Rayl TJ,Kimball FS,Leung D,Hoover HS,Apodaca RL,Breitenbucher JG,Cravatt BF,Boger DL

    更新日期：2007-03-08 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

    doi：10.1021/acs.jmedchem.6b01766

    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

  • Identification of peptide substrate and small molecule inhibitors of testis-specific serine/threonine kinase1 (TSSK1) by the developed assays.

    abstract：:In this paper, a peptide substrate (Pep8) of TSSK1 is identified. Using Pep8 as a substrate, two homogeneous and efficient assays for TSSK1 inhibitors screening have been developed, including luminescent kinase assay and LC-MS-based high-throughput assay. Two classes of compounds were identified that are able to effic...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9002846

    authors： Zhang L,Yan Y,Liu Z,Abliz Z,Liu G

    更新日期：2009-07-23 00:00:00

  • Non-nucleoside inhibitors of HIV-1 reverse transcriptase: molecular modeling and X-ray structure investigations.

    abstract：:The structural features of a new class of non-nucleoside HIV-1 reverse transcriptase inhibitors (3) are presented. Comparison of the structural and electronic properties with those of TIBO (1) and Nevirapine (2) yields a common three-dimensional model. This model permits the improvement of the lead compound 3 by chemi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00058a009

    authors： Schäfer W,Friebe WG,Leinert H,Mertens A,Poll T,von der Saal W,Zilch H,Nuber B,Ziegler ML

    更新日期：1993-03-19 00:00:00

  • Hydantoin-substituted 4,6-dichloroindole-2-carboxylic acids as ligands with high affinity for the glycine binding site of the NMDA receptor.

    abstract：:A novel series of C-3 substituted 4,6-dichloroindole-2-carboxylic acids was synthesized to investigate the influence of different hydrogen-bond donor and acceptor groups at this specific position on the affinity to the glycine site of the NMDA receptor. These novel 3-indolylmethyl derivatives with ring-open (amines, s...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm020955n

    authors： Jansen M,Potschka H,Brandt C,Löscher W,Dannhardt G

    更新日期：2003-01-02 00:00:00

  • Low molecular weight, non-peptide fibrinogen receptor antagonists.

    abstract：:The tetrapeptide H-Arg-Gly-Asp-Ser-OH (1) (RGDS), representing a recognition sequence of fibrinogen for its platelet receptor GP IIb-IIIa (integrin alpha IIb beta 3), served as lead compound for the development of highly potent and selective fibrinogen receptor antagonists. Replacement of the N-terminal arginine by p-...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00101a017

    authors： Alig L,Edenhofer A,Hadváry P,Hürzeler M,Knopp D,Müller M,Steiner B,Trzeciak A,Weller T

    更新日期：1992-11-13 00:00:00