当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Structure activity relationships of benzylproline-derived inhibitors of the glutamine transporter ASCT2.

Structure activity relationships of benzylproline-derived inhibitors of the glutamine transporter ASCT2.

Abstract：

:The glutamine transporter ASCT2 has been identified as a promising target to inhibit rapid growth of cancer cells. However, ASCT2 pharmacology is not well established. In this report, we performed a systematic structure activity analysis of a series of substituted benzylproline derivatives. Substitutions on the phenyl ring resulted in compounds with characteristics of ASCT2 inhibitors. Apparent binding affinity increased with increasing hydrophobicity of the side chain. In contrast, interaction of the ASCT2 binding site with specific positions on the phenyl ring was not observed. The most potent compound inhibits the ASCT2 anion conductance with a Ki of 3μM, which is in the same range as that of more bulky and higher molecular weight inhibitors recently reported by others. The experimental results are consistent with computational analysis based on docking of the inhibitors against an ASCT2 homology model. The benzylproline scaffold provides a valuable tool for further improving binding potency of future ASCT2 inhibitors.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Singh K,Tanui R,Gameiro A,Eisenberg G,Colas C,Schlessinger A,Grewer C

doi

10.1016/j.bmcl.2016.12.063

subject

Has Abstract

pub_date

2017-02-01 00:00:00

pages

398-402

issue

3

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(16)31343-9

journal_volume

27

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • 1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides as potent factor Xa inhibitors. Part 2: A survey of P4 motifs.

    abstract：:A variety of P4 motifs have been examined to increase the binding affinity and in vitro anticoagulant potency of our biphenyl 1-(2-naphthyl)-1H-pyrazole-5-carboxylamide-based fXa inhibitors. Highly potent 2-naphthyl-P1 fXa inhibitors (K(i)< or =2 nM) with improved in vitro anticoagulant activity (2xTG< or =1 microM) a...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.12.053

    authors： Jia ZJ,Wu Y,Huang W,Zhang P,Clizbe LA,Goldman EA,Sinha U,Arfsten AE,Edwards ST,Alphonso M,Hutchaleelaha A,Scarborough RM,Zhu BY

    更新日期：2004-03-08 00:00:00

  • Solid-phase synthesis of quinol fatty alcohols, design of N/O-substituted quinol fatty alcohols and comparative activities on axonal growth.

    abstract：:Following the promising activity of Q2FA15 on axonal growth, two new series of N/O-substituted QFAs were synthesized, based on a SN2-type reaction. O-alkylated QFA bearing 14 carbon atoms on the side chain (n=14) shows a very potent activity on axonal growth though lowered when compared to Q2FA15. While O-alkylation a...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.05.027

    authors： Hanbali M,Bagnard D,Luu B

    更新日期：2006-08-01 00:00:00

  • 16Beta-hydroxy-5alpha-cholestane-3,6-dione, a novel cytotoxic oxysterol from the red alga Jania rubens.

    abstract：:A new cytotoxic oxysterol, 16beta-hydroxy-5alpha-cholestane-3,6-dione was isolated from the red alga Jania rubens. Its structure was established by spectroscopic method. The ID50 value was 0.5 microg/mL. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00504-7

    authors： Ktari L,Blond A,Guyot M

    更新日期：2000-11-20 00:00:00

  • Anti-tumor abietane diterpenes from the cones of Sequoia sempervirens.

    abstract：:A new abietane, namely, 20-hydroxyferruginol (1), together with known ferruginol (2), 18-hydroxyferruginol (3), sugiol (4), and 6alpha-hydroxysugiol (5), were isolated from the cones of Sequoia sempervirens. Their structures were elucidated through spectral data. Compounds 1 and 5 strongly inhibited colon, lung, and b...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.02.057

    authors： Son KH,Oh HM,Choi SK,Han DC,Kwon BM

    更新日期：2005-04-15 00:00:00

  • (S)-N-(5-Chlorothiophene-2-sulfonyl)-beta,beta-diethylalaninol a Notch-1-sparing gamma-secretase inhibitor.

    abstract：:Accumulation of beta-amyloid (Abeta), produced by the proteolytic cleavage of amyloid precursor protein (APP) by beta- and gamma-secretase, is widely believed to be associated with Alzheimer's disease (AD). Research around the high-throughput screening hit (S)-4-chlorophenylsulfonyl isoleucinol led to the identificati...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.11.116

    authors： Cole DC,Stock JR,Kreft AF,Antane M,Aschmies SH,Atchison KP,Casebier DS,Comery TA,Diamantidis G,Ellingboe JW,Harrison BL,Hu Y,Jin M,Kubrak DM,Lu P,Mann CW,Martone RL,Moore WJ,Oganesian A,Riddell DR,Sonnenberg-Reine

    更新日期：2009-02-01 00:00:00

  • Discovery of potent, selective, and orally bioavailable PDE5 inhibitor: Methyl-4-(3-chloro-4-methoxybenzylamino)-8-(2-hydroxyethyl)-7-methoxyquinazolin-6-ylmethylcarbamate (CKD 533).

    abstract：:In a continuing effort to discover novel PDE5 inhibitors, we have successfully found quinazolines with 4-benzylamino substitution as potent and selective PDE5 inhibitors. Initial lead compound (1) was found to be easily metabolized when incubated with human liver microsomes mainly through C6 amide hydrolysis. Blocking...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.10.071

    authors： Choi H,Lee J,Kim YH,Im DS,Hwang IC,Kim SJ,Moon SK,Lee HW,Lee SS,Ahn SK,Kim SW,Choi NS,Lee KJ

    更新日期：2010-01-01 00:00:00

  • Identification of prostaglandin D2 receptor antagonists based on a tetrahydropyridoindole scaffold.

    abstract：:A new series of indole-based antagonists of the PGD(2) receptor subtype 1 (DP1 receptor) was identified and the progress of the structure-activity relationship study to the identification of potent and selective antagonists is presented. Selective DP1 antagonists with high potency and selectivity were prepared. Of par...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.03.015

    authors： Beaulieu C,Guay D,Wang Z,Leblanc Y,Roy P,Dufresne C,Zamboni R,Berthelette C,Day S,Tsou N,Denis D,Greig G,Mathieu MC,O'Neill G

    更新日期：2008-04-15 00:00:00

  • Inhibition of HIV-1 infection by synthetic peptide analogues derived from the NH(2)-Terminal extracellular region of GPR1.

    abstract：:Several shortened peptide analogues of the N-terminal domain of GPR1, an orphan G protein-coupled receptor (GPCR), were prepared and their anti-HIV-1 activities were evaluated. Some of the prepared compounds, especially sulfated derivatives, showed potent inhibitory activity against a broad range of HIV-1, including T...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00503-0

    authors： Ikeda K,Konishi K,Sato M,Hoshino H,Tanaka K

    更新日期：2001-10-08 00:00:00

  • Effect of linker substitution on the binding of butorphan univalent and bivalent ligands to opioid receptors.

    abstract：:A series of bivalent hydroxy ether butorphan ligands were prepared and their binding affinities at the opioid receptors determined. Addition of a hydroxy group to a hydrocarbon chain can potentiate binding affinity up to 27- and 86-fold at the mu and kappa opioid receptors, respectively. Two bivalent ligands with sub-...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.01.101

    authors： Fulton BS,Knapp BL,Bidlack JM,Neumeyer JL

    更新日期：2010-03-01 00:00:00

  • The bioisosteric modification of pyrazinamide derivatives led to potent antitubercular agents: Synthesis via click approach and molecular docking of pyrazine-1,2,3-triazoles.

    abstract：:Tuberculosis remains as a major public health risk which causes the highest mortality rate globally and an improved regimen is required to treat the drug-resistant strains. Pyrazinamide is a first-line antitubercular drug used in combination therapy with other anti-TB drugs. Herein, we describe the modification of pyr...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2019.126846

    authors： Reddyrajula R,Dalimba U

    更新日期：2020-01-15 00:00:00

  • 6-Triazolyl-substituted sulfocoumarins are potent, selective inhibitors of the tumor-associated carbonic anhydrases IX and XII.

    abstract：:A series of 6-substituted sulfocoumarins incorporating substituted-1,2,3-triazol-4-yl-/5-yl moieties were synthesized by employing click chemistry. The new sulfocoumarins incorporated cycloalkyl, tert-butyl and substituted aryl moieties at the triazole ring, and were investigated for the inhibition of four human (h) c...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.01.076

    authors： Grandane A,Tanc M,Zalubovskis R,Supuran CT

    更新日期：2014-03-01 00:00:00

  • In vitro evolution of an HIV integrase binding protein from a library of C-terminal domain γS-crystallin variants.

    abstract：:A protein without natural binding functions was engineered to bind HIV-1 integrase. Phage display selections applied a library of variants based on the C-terminal domain of the eye lens protein human γS-crystallin. Multiple loop regions were altered to encode libraries with ≈3.6 × 10(11) different variants. A crystall...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.07.008

    authors： Moody IS,Verde SC,Overstreet CM,Edward Robinson W Jr,Weiss GA

    更新日期：2012-09-01 00:00:00

  • Inhibition of lysosomal cysteine proteases by chrysotherapeutic compounds: a possible mechanism for the antiarthritic activity of Au(I).

    abstract：:Although Au(I) complexes have been used to treat rheumatoid arthritis for over 75 years, their mechanism of action is still poorly understood. A family of enzymes responsible for joint destruction in rheumatoid arthritis, the cathepsins, has been discussed as a possible biological target of Au(I). In this study, inhib...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.07.073

    authors： Chircorian A,Barrios AM

    更新日期：2004-10-18 00:00:00

  • Synthesis and structure-activity relationships of oxime neurokinin antagonists: discovery of potent arylamides.

    abstract：:The structural modification of the benzylic ether region of oxime 1 has resulted in the identification of several novel aryl amides as selective or dual NK(1)/NK(2) antagonists. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00709-0

    authors： Shih NY,Albanese M,Anthes JC,Carruthers NI,Grice CA,Lin L,Mangiaracina P,Reichard GA,Schwerdt J,Seidl V,Wong SC,Piwinski JJ

    更新日期：2002-01-21 00:00:00

  • Discovery of an exceptionally potent and selective class of fatty acid amide hydrolase inhibitors enlisting proteome-wide selectivity screening: concurrent optimization of enzyme inhibitor potency and selectivity.

    abstract：:The concurrent implementation of a proteome-wide serine hydrolase selectivity screen with traditional efforts to optimize fatty acid amide hydrolase (FAAH) inhibition potency led to the expedited discovery of a new class of exceptionally potent (Ki < 300 pM) and unusually selective (> 100-fold selective) inhibitors. T...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.12.085

    authors： Leung D,Du W,Hardouin C,Cheng H,Hwang I,Cravatt BF,Boger DL

    更新日期：2005-03-01 00:00:00

  • Design and synthesis of 4-[3,5-dioxo-11-oxa-4,9-diazatricyclo[5.3.1.0(2,6)]undec-4-yl]-2-trifluoromethyl-benzonitriles as androgen receptor antagonists.

    abstract：:A novel series of 4-[3,5-dioxo-11-oxa-4,9-diazatricyclo[5.3.1.0(2,6)]undec-4-yl]-2-trifluoromethyl-benzonitriles has been synthesized. The ability of these compounds to act as antagonists of the androgen receptor was investigated and several were found to have potent activity in vitro and in vivo. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.06.034

    authors： Xiao HY,Balog A,Attar RM,Fairfax D,Fleming LB,Holst CL,Martin GS,Rossiter LM,Chen J,Cvjic ME,Dell-John J,Geng J,Gottardis MM,Han WC,Nation A,Obermeier M,Rizzo CA,Schweizer L,Spires T Jr,Shan W,Gavai A,Salvati ME

    更新日期：2010-08-01 00:00:00

  • Thiazolo[4,5-d]pyrimidine thiones and -ones as corticotropin-releasing hormone (CRH-R1) receptor antagonists.

    abstract：:A series of thiazolo[4,5-d]pyrimidine thiones and -ones was prepared and discovered to have good binding affinity to the CRH-R1 receptor, thus showing promise as a new class of potential anxiolytics and/or antidepressants. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00159-6

    authors： Beck JP,Curry MA,Chorvat RJ,Fitzgerald LW,Gilligan PJ,Zaczek R,Trainor GL

    更新日期：1999-04-19 00:00:00

  • Synthesis and thrombolytic activity of fibrinogen fragment related cyclopeptides.

    abstract：:In the modification of the fibrinogen fragment related sequences ARPAK, QRPAK GRPAK and KRPAK, the corresponding cyclo-ARPAK, cyclo-QRPAK, cyclo-GRPAK, and cyclo-KRPAK were prepared in the diluted solution. The bioassay in vivo indicated that the thrombolytic potencies of cyclo-ARPAK, cyclo-GRPAK, cyclo-QRPAK, and cyc...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)01072-7

    authors： Zhao M,Lin N,Wang C,Peng S

    更新日期：2003-03-10 00:00:00

  • 3,4-Dihydro-1-isoquinolinamines: a novel class of nitric oxide synthase inhibitors with a range of isoform selectivity and potency.

    abstract：:3-Phenyl-3.4-dihydro-1-isoquinolinamine is a weak inhibitor of iNOS and nNOS. Structural variation of 5a results in inhibitors with a range of potency and selectivity for the NOS enzymes, including a potent and very selective iNOS inhibitor 5j. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00119-6

    authors： Beaton H,Hamley P,Nicholls DJ,Tinker AC,Wallace AV

    更新日期：2001-04-23 00:00:00

  • Evaluation of licorice flavonoids as protein tyrosine phosphatase 1B inhibitors.

    abstract：:Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator in insulin- and leptin-signaling cascades as well as a positive regulator in tumorigenesis, and much attention has been paid to PTP1B inhibitors as potential therapies for diabetes, obesity, and cancer. In the present study, the screening of a compo...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.08.102

    authors： Li W,Li S,Higai K,Sasaki T,Asada Y,Ohshima S,Koike K

    更新日期：2013-11-01 00:00:00

  • The SAR of 4-substituted (6,6-bicyclic) piperidine cathepsin S inhibitors.

    abstract：:A series of competitive, reversible cathepsin S (CatS) inhibitors was investigated. An earlier disclosure detailed the discovery of the 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety as an effective replacement for the 4-arylpiperazin-1-yl group found in our screening hit. Continued investigation into replacement...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.01.038

    authors： Grice CA,Tays K,Khatuya H,Gustin DJ,Butler CR,Wei J,Sehon CA,Sun S,Gu Y,Jiang W,Thurmond RL,Karlsson L,Edwards JP

    更新日期：2006-04-15 00:00:00

  • Syntheses and antiproliferative evaluation of oxyphenisatin derivatives.

    abstract：:Syntheses and structure-antiproliferative relationship for oxyphenisatin analogues are described. The cell proliferation data showed that the presence of substituents (especially F, Cl, Me, CF(3), and OMe) in the 6- and 7-position of oxyphenisatin markedly enhanced the potency in the MDA-468 cell line without affectin...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.02.060

    authors： Uddin MK,Reignier SG,Coulter T,Montalbetti C,Grånäs C,Butcher S,Krog-Jensen C,Felding J

    更新日期：2007-05-15 00:00:00

  • Synthesis and protective effects of coumarin derivatives against oxidative stress induced by doxorubicin.

    abstract：:The use of doxorubicin (DOX) in the treatment of solid tumors is limited by cardiotoxicity essentially due to oxidative stress generation. The aim of this study was to identify coumarin derivatives displaying a protective antioxidant activity without affecting DOX antitumoral efficiency. A set of eighteen coumarinic d...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.12.004

    authors： Beillerot A,Domínguez JC,Kirsch G,Bagrel D

    更新日期：2008-02-01 00:00:00

  • Structural and stereochemical requirements of the spiroketal group of hippuristanol for antiproliferative activity.

    abstract：:Hippuristanol is a natural product that has recently been shown to inhibit eukaryotic translation initiation and tumor cell proliferation. To investigate the structure and activity relationship of hippuristanol, we synthesized a series of analogs by expanding the size of its F ring and determined their effects on the ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.03.093

    authors： Li W,Dang Y,Liu JO,Yu B

    更新日期：2010-05-15 00:00:00

  • Structure-activity relationship of cyclic peptide penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2) at the human melanocortin-1 and -4 receptors: His(6) substitution.

    abstract：:A series of MT-II related cyclic peptides, based on potent but non-selective hMC4R agonist (Penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2)) was prepared in which His(6) residue was systematically substituted. Two of the most interesting peptides identified in this study are Penta-c[Asp-5-ClAtc-DPhe-Arg-Trp-Lys]-N...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00114-8

    authors： Cheung AW,Danho W,Swistok J,Qi L,Kurylko G,Rowan K,Yeon M,Franco L,Chu XJ,Chen L,Yagaloff K

    更新日期：2003-04-07 00:00:00

  • Highly potent activity of isopulegol-derived substituted octahydro-2H-chromen-4-ols against influenza A and B viruses.

    abstract：:A set of (-)-isopulegol derived octahydro-2H-chromen-4-ols was synthesized and evaluated in vitro for antiviral activity against panel of reference influenza virus strains differing in subtype, origin (human or avian) and drug resistance. Compound (4R)-11a produced via one-pot synthesis by interaction between (-)-isop...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.04.057

    authors： Ilyina IV,Zarubaev VV,Lavrentieva IN,Shtro AA,Esaulkova IL,Korchagina DV,Borisevich SS,Volcho KP,Salakhutdinov NF

    更新日期：2018-06-15 00:00:00

  • Kelsoenethiol and dikelsoenyl ether, two unique kelsoane-type sesquiterpenes, from the Formosan soft coral Nephthea erecta.

    abstract：:Two new kelsoane-type sesquiterpenes, namely kelsoenethiol (1) and dikelsoenyl ether (2), were obtained from the Formosan soft coral Nephthea erecta. Their structures were elucidated through extensive spectroscopic analyses, ESI orbitrap mass and quantum chemical calculations (QCC). The cytotoxicity against A-459 (hum...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.12.037

    authors： Cheng SY,Shih NL,Hou KY,Ger MJ,Yang CN,Wang SK,Duh CY

    更新日期：2014-01-15 00:00:00

  • Synthesis and properties of prodrugs activated in hypoxia to give bleomycin analogues.

    abstract：:Prodrugs bioreductively activated to bleomycin analogues are reported. The production of hydroxyl radicals in the presence of FE(II) and dioxygen by both the prodrugs and the activated products are determined and their in vitro cytotoxicity measured. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00467-3

    authors： Highfield JA,Mehta LK,Parrick J,Candeias LP,Wardman P

    更新日期：1998-09-22 00:00:00

  • The discovery of potent glycine transporter type-2 inhibitors: design and synthesis of phenoxymethylbenzamide derivatives.

    abstract：:We describe the discovery of phenoxymethylbenzamide derivatives as a novel class of glycine transporter type-2 (GlyT-2) inhibitors. We found hit compound 1 (human GlyT-2, IC50=4040 nM) in our library and converted its 1-(1-(naphthalen-2-ylmethyl)piperidin-4-yl)pyrrolidin-3-yl group to an 1-(N,N-dimethylaminopropyl)pip...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.06.059

    authors： Takahashi E,Arai T,Akahira M,Nakajima M,Nishimura K,Omori Y,Kumagai H,Suzuki T,Hayashi R

    更新日期：2014-09-15 00:00:00

  • Effect of structural modification on the inhibitory selectivity of rutaecarpine derivatives on human CYP1A1, CYP1A2, and CYP1B1.

    abstract：:Derivatives of a CYP1A2 inhibitor rutaecarpine were synthesized to have potent and selective inhibition of human CYP1 members. Structural modelling shows a good fitting of rutaecarpine with the putative active site of human CYP1A2. Among the derivatives, 10- and 11-methoxyrutaecarpine are the most selective CYP1B1 inh...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00469-4

    authors： Don MJ,Lewis DF,Wang SY,Tsai MW,Ueng YF

    更新日期：2003-08-04 00:00:00