当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Structure-based design of novel human Pin1 inhibitors (III): optimizing affinity beyond the phosphate recognition pocket.

Structure-based design of novel human Pin1 inhibitors (III): optimizing affinity beyond the phosphate recognition pocket.

Abstract：

:The design of potent Pin1 inhibitors has been challenging because its active site specifically recognizes a phospho-protein epitope. The de novo design of phosphate-based Pin1 inhibitors focusing on the phosphate recognition pocket and the successful replacement of the phosphate group with a carboxylate have been previously reported. The potency of the carboxylate series is now further improved through structure-based optimization of ligand-protein interactions in the proline binding site which exploits the H-bond interactions necessary for Pin1 catalytic function. Further optimization using a focused library approach led to the discovery of low nanomolar non-phosphate small molecular Pin1 inhibitors. Structural modifications designed to improve cell permeability resulted in Pin1 inhibitors with low micromolar anti-proliferative activities against cancer cells.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Guo C,Hou X,Dong L,Marakovits J,Greasley S,Dagostino E,Ferre R,Johnson MC,Humphries PS,Li H,Paderes GD,Piraino J,Kraynov E,Murray BW

doi

10.1016/j.bmcl.2014.07.044

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

4187-91

issue

17

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(14)00768-9

journal_volume

24

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • New diarylureas and diarylamides possessing acet(benz)amidophenyl scaffold: design, synthesis, and antiproliferative activity against melanoma cell line.

    abstract：:A series of new diarylurea and diarylamide derivatives possessing acet(benz)amidophenyl scaffold was synthesized. Their in vitro antiproliferative activity was tested against A375P human melanoma cell line. Compounds 1c,d and 2c,d showed the highest potencies with IC(50) values in sub-micromolar scale. In addition, co...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.03.020

    authors： Kim HJ,Cho HJ,Kim H,El-Gamal MI,Oh CH,Lee SH,Sim T,Hah JM,Yoo KH

    更新日期：2012-05-01 00:00:00

  • Trityl radicals in perfluorocarbon emulsions as stable, sensitive, and biocompatible oximetry probes.

    abstract：:EPR oximetry with the use of trityl radicals can enable sensitive O2 measurement in biological cells and tissues. However, in vitro cellular and in vivo biological applications are limited by rapid trityl probe degradation or biological clearance and the need to enhance probe O2 sensitivity. We synthesized novel perfl...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.10.066

    authors： Dhimitruka I,Alzarie YA,Hemann C,Samouilov A,Zweier JL

    更新日期：2016-12-01 00:00:00

  • Effect of the oligo(ethylene glycol) group on the antioxidant activity of manganese salen complexes.

    abstract：:The synthesis and antioxidant activity of oligo(ethylene glycol)-modified manganese salen complexes are reported. Their SOD activities were similar and 2- to 3-fold more potent than the standard compound EUK-134. Their catalase-like activity was lower than that of EUK-134 in the initial conversion rate; however, some ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.12.063

    authors： Park W,Lim D

    更新日期：2009-02-01 00:00:00

  • Design, synthesis and biological evaluation of novel semicarbazone-selenochroman-4-ones hybrids as potent antifungal agents.

    abstract：:A series of novel 2,3-dihydro-4H-1-benzoselenin-4-one (thio)semicarbazone derivatives were designed and synthesized by using molecular hybridization approach. All the target compounds were characterized by HRMS and NMR and evaluated in vitro antifungal activity against five pathogenic strains. In comparison with precu...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2019.126726

    authors： Xu H,Su X,Liu XQ,Zhang KP,Hou Z,Guo C

    更新日期：2019-12-01 00:00:00

  • Suzuki coupling based synthesis and in vitro cytotoxic evaluation of 7-heteroaryl-substituted camptothecin analogs.

    abstract：:In an effort to discover potent antitumor agents, a series of novel C-7-heteroaryl-substituted camptothecin derivatives were designed and synthesized via microwave-promoted Suzuki coupling reaction. These analogs were then assessed for cytotoxicity against three human tumor cell lines, A549, HCT116, HT-29, and inhibit...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.01.049

    authors： Wang L,Huang Y,Zhang J,Tong L,Chen Y,Lu W,Huang Q

    更新日期：2014-03-15 00:00:00

  • Synthesis and SAR of 5,6-diarylpyridines as human CB1 inverse agonists.

    abstract：:Structure-activity relationship studies for two series of 2-benzyloxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyridines having either a 3-cyano or 3-carboxamide moiety resulted in the preparation of the 2-(3,4-difluorobenzyloxy)-3-nitrile analog 10d and the 2-(3,4-difluorobenzyloxy)-3-(N-propylcarboxamide) analog 16c...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.11.031

    authors： Meurer LC,Finke PE,Mills SG,Walsh TF,Toupence RB,Debenham JS,Goulet MT,Wang J,Tong X,Fong TM,Lao J,Schaeffer MT,Chen J,Shen CP,Sloan Stribling D,Shearman LP,Strack AM,Van der Ploeg LH

    更新日期：2005-02-01 00:00:00

  • Oxidative calcium release from catechol.

    abstract：:Oxidation of 4-methylcatechol previously exposed to aqueous calcium chloride was shown by ion chromatography to be associated with release of calcium ions. The catechol was oxidised to the corresponding orthoquinone by the use of tyrosinase from Agaricus bisporus. The oxidative release of calcium from the catechol is ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.02.036

    authors： Riley PA,Stratford MR

    更新日期：2015-04-01 00:00:00

  • Photo-controlled binding of MutS to photo-caged DNA duplexes incorporating 4-O-(2-nitrobenzyl) or 4-O-[2-(2-nitrophenyl)propyl]thymidine.

    abstract：:Mismatch binding protein MutS binding to bulge structure in DNA duplexes was controlled by UV irradiation. 4-O-(2-Nitrobenzyl)thymidine or 4-O-[2-(2-nitrophenyl)propyl]thymidine was incorporated into DNA duplexes a bulged position. The MutS did not bind to the caged DNA duplexes but bound after removing the 2-nitroben...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.07.075

    authors： Seio K,Ohno Y,Ohno K,Takeshita L,Kanamori T,Masaki Y,Sekine M

    更新日期：2016-10-01 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

  • Design and synthesis of novel RXR-selective modulators with improved pharmacological profile.

    abstract：:New RXR-selective modulators possessing a 6-fluoro trienoic acid moiety (6Z olefin) or a fluorinated/heterocyclic-substituted benzene core ring, were synthesized in an expedient and selective way. A subset of these compounds was evaluated for their metabolic properties (exposure in IRC male mice) and show a dramatic i...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.08.048

    authors： Michellys PY,Boehm MF,Chen JH,Grese TA,Karanewsky DS,Leibowitz MD,Liu S,Mais DA,Mapes CM,Reifel-Miller A,Ogilvie KM,Rungta D,Thompson AW,Tyhonas JS,Yumibe N,Ardecky RJ

    更新日期：2003-11-17 00:00:00

  • Synthesis of cholestane glycosides bearing OSW-1 disaccharide or its 1-->4-linked analogue and their antitumor activities.

    abstract：:For further structure-activity relationship (SAR) research of OSW saponins, a cholestane glycoside, namely 3beta, 16beta, 26-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-beta-D-xylopyranosyl)-(1-->3)-2-O-acetyl-alpha-L-arabinopyranoside (1) together with two 1-->4-linked disaccharide analogues (2 and 3) we...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.07.085

    authors： Zheng D,Zhou L,Guan Y,Chen X,Zhou W,Chen X,Lei P

    更新日期：2010-09-15 00:00:00

  • Design and synthesis of small molecular dual inhibitor of falcipain-2 and dihydrofolate reductase as antimalarial agent.

    abstract：:Resistance of malaria parasites has quickly developed to almost all used antimalarial drugs. Accordingly, the discovery of new effective drugs to counter the spread of malaria parasites that are resistant to existing agents, especially acting on multi-targets, is an urgent need. The cysteine protease falcipain-2 (FP-2...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.12.011

    authors： Huang H,Lu W,Li X,Cong X,Ma H,Liu X,Zhang Y,Che P,Ma R,Li H,Shen X,Jiang H,Huang J,Zhu J

    更新日期：2012-01-15 00:00:00

  • A new class of histamine H(3)-receptor antagonists: synthesis and structure-activity relationships of 7,8,9,10-tetrahydro-6H-cyclohepta[b]quinolines.

    abstract：:The synthesis and biological evaluation of novel cycloheptaquinoline antagonists of the human H(3) receptor are described. Two series of compounds, bearing either an amino substituent or an alkyne linker at the 11-position, were investigated. Modifications of the amino substituents, optimization of chain length and th...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00356-1

    authors： Turner SC,Esbenshade TA,Bennani YL,Hancock AA

    更新日期：2003-07-07 00:00:00

  • Methanesulfonamide group at position-4 of the C-5-phenyl ring of 1,5-diarylpyrazole affords a potent class of cyclooxygenase-2 (COX-2) inhibitors.

    abstract：:The effect of methanesulfonamide (MeSO(2)NH) group on COX-2 inhibitory activity of 1,5-diarylpyrazole is described. While this group being at position-4 of the N(1)-phenyl ring was found to be ineffective, its installation at position-4 of the C-5 phenyl ring offered several potent and selective inhibitors of COX-2 wi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.01.053

    authors： Singh SK,Vobbalareddy S,Shivaramakrishna S,Krishnamraju A,Rajjak SA,Casturi SR,Akhila V,Rao YK

    更新日期：2004-04-05 00:00:00

  • Sugar Chips immobilized with synthetic sulfated disaccharides of heparin/heparan sulfate partial structure.

    abstract：:Carbohydrate chip technology has a great potential for the high-throughput evaluation of carbohydrate-protein interactions. Herein, we report syntheses of novel sulfated oligosaccharides possessing heparin and heparan sulfate partial disaccharide structures, their immobilization on gold-coated chips to prepare array-t...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.01.069

    authors： Wakao M,Saito A,Ohishi K,Kishimoto Y,Nishimura T,Sobel M,Suda Y

    更新日期：2008-04-01 00:00:00

  • Discovery of 3-aminopicolinamides as metabotropic glutamate receptor subtype 4 (mGlu4) positive allosteric modulator warheads engendering CNS exposure and in vivo efficacy.

    abstract：:This letter describes the further chemical optimization of the picolinamide-derived family of mGlu4 PAMs wherein we identified a 3-amino substituent to the picolinamide warhead that engendered potency, CNS penetration and in vivo efficacy. From this optimization campaign, VU0477886 emerged as a potent (EC50=95nM, 89% ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.04.041

    authors： Gogliotti RD,Engers DW,Garcia-Barrantes PM,Panarese JD,Gentry PR,Blobaum AL,Morrison RD,Daniels JS,Thompson AD,Jones CK,Conn PJ,Niswender CM,Lindsley CW,Hopkins CR

    更新日期：2016-06-15 00:00:00

  • Nitrobenzene compounds inhibit expression of VCAM-1.

    abstract：:A series of nitrobenzene compounds has been discovered as potent inhibitors of VCAM-1 expression and, therefore, potential drug candidates for autoimmune and allergic inflammatory diseases. Structure-activity relationship (SAR) studies showed that a nitro group and two other electron-withdrawing groups are essential f...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00306-7

    authors： Meng CQ,Zheng XS,Holt LA,Hoong LK,Somers PK,Hill RR,Saxena U

    更新日期：2001-07-23 00:00:00

  • Discovery of novel antagonists of glycoprotein IIb/IIIa-mediated platelet aggregation through virtual screening.

    abstract：:The glycoprotein IIb/IIIa receptor is the final common pathway of platelet aggregation, regardless of the agonist, and thus represents an ideal therapeutic target for blocking thrombus formation. RUC-2 is a novel glycoprotein IIb/IIIa inhibitor of adenosine-5'-diphosphate (ADP)-induced platelet aggregation, importantl...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.01.053

    authors： Wang Y,Zhao Y,Sun R,Kong W,Wang B,Yang G,Li Y

    更新日期：2015-03-15 00:00:00

  • N-carbamoyl analogs of Zafirlukast: potent receptor antagonists of leukotriene D4.

    abstract：:Exploration of the indole nitrogen region of Zafirlukast (1) has uncovered a potent series of cysteinyl leukotriene D4 (LTD4) antagonists. These studies showed that a variety of functionality could be incorporated in this region of the molecule without sacrificing potency. Efforts to exploit this site in order to impr...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00442-9

    authors： Brown MF,Marfat A,Antognoli G,Chambers RJ,Cheng JB,Damon DB,Liston TE,McGlynn MA,O'Sullivan SP,Owens BS,Pillar JS,Shirley JT,Watson JW

    更新日期：1998-09-22 00:00:00

  • Discovery of new peptide-based catalysts for the direct asymmetric aldol reaction.

    abstract：:A series of oligo-peptide based catalysts were prepared using Fmoc solid-phase peptide synthesis. It was found that peptides with N-terminal proline residues catalyzed an aldol reaction yielding enantiomeric enriched product. Peptide H-Pro-Glu-Leu-Phe-OH catalyzed the reaction with good activity and moderate enantiose...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00498-0

    authors： Kofoed J,Nielsen J,Reymond JL

    更新日期：2003-08-04 00:00:00

  • 4,4-Dimethyl-1,2,3,4-tetrahydroquinoline-based PPARalpha/gamma agonists. Part. II: Synthesis and pharmacological evaluation of oxime and acidic head group structural variations.

    abstract：:Type-2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance in the liver and peripheral tissues accompanied by a deficiency in pancreatic beta-cells. Since their discovery, three subtypes of peroxisome proliferator activated receptors have been identified, namely PPARalpha, PPARgamma and P...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.03.143

    authors： Parmenon C,Guillard J,Caignard DH,Hennuyer N,Staels B,Audinot-Bouchez V,Boutin JA,Dacquet C,Ktorza A,Viaud-Massuard MC

    更新日期：2009-05-15 00:00:00

  • Discovery of a novel melanin concentrating hormone receptor 1 (MCHR1) antagonist with reduced hERG inhibition.

    abstract：:An initial SAR study resulted in the identification of the novel, potent MCHR1 antagonist 2. After further profiling, compound 2 was discovered to be a potent inhibitor of the hERG potassium channel, which prevented its further development. Additional optimization of this structure resulted in the discovery of the pot...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.04.006

    authors： Mihalic JT,Fan P,Chen X,Chen X,Fu Y,Motani A,Liang L,Lindstrom M,Tang L,Chen JL,Jaen J,Dai K,Li L

    更新日期：2012-06-01 00:00:00

  • Syntheses and biological evaluation of new fluoroquinolone antibacterials containing chiral oxiimino pyrrolidine.

    abstract：:The design and syntheses of new fluoroquinolone antibacterial agents having pyrrolidine ring at C-7 position are described. The pyrrolidine ring is optically active and possesses methyloxime functional group. Two of them have excellent in vitro antibacterial activities and pharmacokinetic profiles. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.12.044

    authors： Choi DR,Shin JH,Yang J,Yoon SH,Jung YH

    更新日期：2004-03-08 00:00:00

  • New tetrahydronaphthalene derivatives as combined thromboxane receptor antagonists and thromboxane synthase inhibitors.

    abstract：:A pyridine group was linked to the tetrahydronaphthalene moiety of the derivatives described in the preceding paper, to afford new combined thromboxane receptor (TP-receptor) antagonists and synthase inhibitors. The most interesting compound 2f inhibits TXA2 synthase with an IC50 value of 0.64 microM and the aggregati...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00221-2

    authors： Cimetière B,Dubuffet T,Landras C,Descombes JJ,Simonet S,Verbeuren TJ,Lavielle G

    更新日期：1998-06-02 00:00:00

  • Enhanced potency of perfluorinated thalidomide derivatives for inhibition of LPS-induced tumor necrosis factor-alpha production is associated with a change of mechanism of action.

    abstract：:Perfluorination of phthalimides leads to dramatically increased potency as inhibitors of TNF-alpha production. We examined the enantiodependence for several tetrafluorophthalimides and alpha-methylthalidomide, 3. Only 3 exhibited strikingly enantiodependent activity. The key structural determinant for the enhanced act...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00171-1

    authors： Niwayama S,Loh C,Turk BE,Liu JO,Miyachi H,Hashimoto Y

    更新日期：1998-05-05 00:00:00

  • Ejection of structural zinc leads to inhibition of γ-butyrobetaine hydroxylase.

    abstract：:γ-Butyrobetaine hydroxylase (BBOX) is a 2-oxoglutarate and Fe(II) dependent oxygenase that catalyses an essential step during carnitine biosynthesis in animals. BBOX is inhibited by ejection of structural zinc by a set of selenium containing analogues. Previous structural analyses indicated that an undisrupted N-termi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.09.035

    authors： Rydzik AM,Brem J,Struwe WB,Kochan GT,Benesch JL,Schofield CJ

    更新日期：2014-11-01 00:00:00

  • Prenylated xanthones as potential P-glycoprotein modulators.

    abstract：:Dimethylallyl (DMA) derivatives of a naturally occurring xanthone (decussatin 1) were prepared. Their activity as potential P-glycoprotein inhibitors was monitored by affinity of direct binding and compared to that of corresponding DMA-flavones. Both classes of compounds exhibited the same structure-activity relations...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00234-1

    authors： Tchamo DN,Dijoux-Franca MG,Mariotte AM,Tsamo E,Daskiewicz JB,Bayet C,Barron D,Conseil G,Di Pietro A

    更新日期：2000-06-19 00:00:00

  • Spirocyclic nonpeptide glycoprotein IIb-IIIa antagonists. Part 2: design of potent antagonists containing the 3-azaspiro[5.5]undecanes.

    abstract：:The synthesis and biological activity of novel glycoprotein IIb-IlIa anatagonists containing 3-azaspiro[5.5]undec-9-yl nucleus are described. The potent activity of these compounds as platelet aggregation inhibitors demonstrates the utility of the monoazaspirocyclic structure as central template for nonpeptide RGD mim...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00216-5

    authors： Pandey A,Seroogy J,Volkots D,Smyth MS,Rose J,Mehrotra MM,Heath J,Ruhter G,Schotten T,Scarborough RM

    更新日期：2001-05-21 00:00:00

  • Synthesis and antiviral evaluation of novel 1,3,4-oxadiazole/thiadiazole-chalcone conjugates.

    abstract：:A series of novel 1,3,4-oxadiazole/thiadiazole-chalcone conjugates were synthesized and their in vitro and in vivo antiviral activities were evaluated via microscale thermophoresis method and half-leaf method, respectively. The in vitro results indicated that compounds 7g, 7l, 8h, and 8l displayed good antiviral activ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.08.038

    authors： Gan X,Hu D,Chen Z,Wang Y,Song B

    更新日期：2017-09-15 00:00:00

  • Decreasing the CYP2D6 contribution to metabolism of a CK1ε inhibitor.

    abstract：:Our internal casein kinase 1ε lead inhibitor, compound 1 was partially cleared by the polymorphic cytochrome P450 2D6. CYP2D6 involvement in metabolism implies more extensive clinical trials. We therefore wanted to reduce the contribution to clearance by this enzyme. We utilized metabolism reports for compound 1 perfo...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.10.031

    authors： Vaz RJ,Li Y,Metz M,Yang D,Shen H,Munson M

    更新日期：2018-12-15 00:00:00