当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Pseudodipeptide inhibitors of protein farnesyltransferase.

Pseudodipeptide inhibitors of protein farnesyltransferase.

Abstract：

:A series of pseudodipeptide amides are described that inhibit Ras protein farnesyltransferase (PFTase). These inhibitors are truncated versions of the C-terminal tetrapeptide (CAAX motif) of Ras that serves as the signal sequence for PFTase-catalyzed protein farnesylation. In contrast to CAAX peptidomimetics previously reported, these inhibitors do not have a C-terminal carboxyl moiety, yet they inhibit farnesylation in vitro at < 100 nM. Despite the absence of the X residue in the CAAX motif, which normally directs prenylation specificity, these pseudodipeptides are greater than 100-fold selective for PFTase over type 1 protein geranylgeranyltransferase.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

deSolms SJ,Deana AA,Giuliani EA,Graham SL,Kohl NE,Mosser SD,Oliff AI,Pompliano DL,Rands E,Scholz TH

doi

10.1021/jm00020a010

subject

Has Abstract,Author List Incomplete

pub_date

1995-09-29 00:00:00

pages

3967-71

issue

20

eissn

0022-2623

issn

1520-4804

journal_volume

38

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Molecular interaction model for the C1B domain of protein kinase C-gamma in the complex with its activator phorbol-12-myristate-13-acetate in water solution and lipid bilayer.

    abstract：:Detailed molecular models of the free C1B domain of protein kinase C-gamma (PKC-gamma) and the C1B domain with its activator phorbol-12-myristate-13-acetate (PMA) in water solution and in the presence of dipalmitoylphosphatidylcholine (DPPC) bilayer are presented. Molecular dynamics of the free C1B domain reveals hydr...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm049786s

    authors： Hritz J,Ulicny J,Laaksonen A,Jancura D,Miskovsky P

    更新日期：2004-12-16 00:00:00

  • Modeling of competitive phosphono amino acid NMDA receptor antagonists.

    abstract：:A pharmacophore for the phosphono amino acid antagonists of the NMDA receptor has been developed using computer-based molecular modeling techniques. An important feature of this model is that a single binding site is proposed for the phosphonic acid moiety. All competitive antagonists we have examined incorporating am...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00087a002

    authors： Whitten JP,Harrison BL,Weintraub HJ,McDonald IA

    更新日期：1992-05-01 00:00:00

  • Synthesis and biological activity of CCK heptapeptide analogues. Effects of conformational constraints and standard modifications on receptor subtype selectivity, functional activity in vitro, and appetite suppression in vivo.

    abstract：:A series of modifications of the CCK7 analogue (des-NH2)Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp-Phe-NH2 was prepared and tested for binding to guinea pig CCK-A and CCK-B receptors and in CCK-A-mediated functional assays. Selected analogues also were tested for appetite suppressant activity in rats. Several conformationally rest...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00094a001

    authors： Holladay MW,Bennett MJ,Tufano MD,Lin CW,Asin KE,Witte DG,Miller TR,Bianchi BR,Nikkel AL,Bednarz L

    更新日期：1992-08-07 00:00:00

  • Synthesis and evaluation of novel polyaminocarboxylate-based antitumor agents.

    abstract：:Iron depletion, using iron chelators targeting transferrin receptor (TfR) and ribonucleotide reductase (RR), is proven to be effective in the treatment of cancer. We synthesized and evaluated novel polyaminocarboxylate-based chelators NETA, NE3TA, and NE3TA-Bn and their bifunctional versions C-NETA, C-NE3TA, and N-NE3...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm701307j

    authors： Chong HS,Ma X,Lee H,Bui P,Song HA,Birch N

    更新日期：2008-04-10 00:00:00

  • Synthetic routes to 4-amino-3-carboxy-beta-carboline derivatives: incidental formation of novel furo[3,4-c]-beta-carbolin-2-ones displaying high affinities for the benzodiazepine receptor.

    abstract：:The synthesis of the first 4-amino-3-carboxy-beta-carboline derivative (35) is described. This synthesis is based on ozonolysis of the 4-vinyl-beta-carboline-3-carboxamide 17 to give the 4-aldehyde 20 and potassium permanganate oxidation of the latter to the 4-carboxylic acid 34 followed by a DPPA-promoted Curtius rea...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00001a024

    authors： Dorey G,Dubois L,Prodo de Carvalho LP,Potier P,Dodd RH

    更新日期：1995-01-06 00:00:00

  • Characterization of the interaction between human alpha-thrombin and methyl 3-(2-methyl-1-oxopropoxy)[1]benzothieno[3,2-b]furan-2-carboxylate (LY806303) using electrospray mass spectrometry and tandem mass spectrometry.

    abstract：:Electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) have been used for the first time to study the interaction of human alpha-thrombin with methyl 3-(2-methyl-1-oxopropoxy)[1]benzothieno[3,2-b]furan-2-carbox ylate (LY806303; 1), a potent and selective inhibitor whose mechanism of ac...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00068a012

    authors： Sall DJ,Kaiser RE Jr

    更新日期：1993-08-06 00:00:00

  • Synthesis and evaluation of radioiodinated (E)-18-iodo-17-octadecenoic acid as a model iodoalkenyl fatty acid for myocardial imaging.

    abstract：:125I-labeled (E)-18-iodo-17-octadecenoic acid (13) has been prepared and evaluated in rats to determine the myocardial uptake and retention and degree of in vivo deiodination of this model iodovinyl-substituted fatty acid, which contains no structural perturbation to inhibit metabolism. This new agent was prepared by ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00367a021

    authors： Knapp FF Jr,Goodman MM,Kabalka GW,Sastry KA

    更新日期：1984-01-01 00:00:00

  • Pyridoimidazolones as novel potent inhibitors of v-Raf murine sarcoma viral oncogene homologue B1 (BRAF).

    abstract：:BRAF is a serine/threonine kinase that is mutated in a range of cancers, including 50-70% of melanomas, and has been validated as a therapeutic target. We have designed and synthesized mutant BRAF inhibitors containing pyridoimidazolone as a new hinge-binding scaffold. Compounds have been obtained which have low nanom...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm801509w

    authors： Niculescu-Duvaz D,Gaulon C,Dijkstra HP,Niculescu-Duvaz I,Zambon A,Ménard D,Suijkerbuijk BM,Nourry A,Davies L,Manne H,Friedlos F,Ogilvie L,Hedley D,Whittaker S,Kirk R,Gill A,Taylor RD,Raynaud FI,Moreno-Farre J,Marais

    更新日期：2009-04-23 00:00:00

  • Deep Learning Enhancing Kinome-Wide Polypharmacology Profiling: Model Construction and Experiment Validation.

    abstract：:The kinome-wide virtual profiling of small molecules with high-dimensional structure-activity data is a challenging task in drug discovery. Here, we present a virtual profiling model against a panel of 391 kinases based on large-scale bioactivity data and the multitask deep neural network algorithm. The obtained model...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b00855

    authors： Li X,Li Z,Wu X,Xiong Z,Yang T,Fu Z,Liu X,Tan X,Zhong F,Wan X,Wang D,Ding X,Yang R,Hou H,Li C,Liu H,Chen K,Jiang H,Zheng M

    更新日期：2020-08-27 00:00:00

  • A comparison of structure-activity relationships between spermidine and spermine analogue antineoplastics.

    abstract：:A systematic investigation of the impact of spermidine analogues both in vitro and in vivo is described. The study characterizes the effects of these analogues on L1210 cell growth, polyamine pools, ornithine decarboxylase, S-adenosyl-L-methionine decarboxylase, spermidine/spermine N1-acetyltransferase, the maintenanc...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm960849j

    authors： Bergeron RJ,Feng Y,Weimar WR,McManis JS,Dimova H,Porter C,Raisler B,Phanstiel O

    更新日期：1997-05-09 00:00:00

  • Optimization of Allosteric With-No-Lysine (WNK) Kinase Inhibitors and Efficacy in Rodent Hypertension Models.

    abstract：:The observed structure-activity relationship of three distinct ATP noncompetitive With-No-Lysine (WNK) kinase inhibitor series, together with a crystal structure of a previously disclosed allosteric inhibitor bound to WNK1, led to an overlay hypothesis defining core and side-chain relationships across the different se...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.7b00708

    authors： Yamada K,Levell J,Yoon T,Kohls D,Yowe D,Rigel DF,Imase H,Yuan J,Yasoshima K,DiPetrillo K,Monovich L,Xu L,Zhu M,Kato M,Jain M,Idamakanti N,Taslimi P,Kawanami T,Argikar UA,Kunjathoor V,Xie X,Yagi YI,Iwaki Y,Ro

    更新日期：2017-08-24 00:00:00

  • Oxidation chemistry of (-)-norepinephrine in the presence of L-cysteine.

    abstract：:The noradrenergic neurotransmitter (-)-norepinephrine (1) is very easily oxidized at physiological pH to an o-quinone (2) that normally cyclizes and subsequently oxidatively polymerizes to black melanin. In this investigation it is demonstrated that L-cysteine (CySH) can divert the melanin pathway by efficiently scave...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm960016t

    authors： Shen XM,Dryhurst G

    更新日期：1996-05-10 00:00:00

  • Development and evaluation of novel phosphotyrosine mimetic inhibitors targeting the Src homology 2 domain of signaling lymphocytic activation molecule (SLAM) associated protein.

    abstract：:Specific interactions between Src homology 2 (SH2) domain-containing proteins and the phosphotyrosine-containing counterparts play significant role in cellular protein tyrosine kinase (PTK) signaling pathways. The SH2 domain inhibitors could potentially serve as drug candidates in treating human diseases. Here we have...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm301610q

    authors： Chu CY,Chang CP,Chou YT,Handoko,Hu YL,Lo LC,Lin JJ

    更新日期：2013-04-11 00:00:00

  • Design and Biological Evaluation of m-Xylene Thioether-Stapled Short Helical Peptides Targeting the HIV-1 gp41 Hexameric Coiled-Coil Fusion Complex.

    abstract：:Short peptide-based inhibition of fusion remains an attractive goal in antihuman immunodeficiency virus (HIV) research based on its potential for the development of technically and economically desirable antiviral agents. Herein, we report the use of the dithiol bisalkylation reaction to generate a series of m-xylene ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b00882

    authors： Meng G,Pu J,Li Y,Han A,Tian Y,Xu W,Zhang T,Li X,Lu L,Wang C,Jiang S,Liu K

    更新日期：2019-10-10 00:00:00

  • Estrogenic potential of 2-alkyl-4-(thio)chromenone 6-O-sulfamates: potent inhibitors of human steroid sulfatase.

    abstract：:2-Alkylchromen-4-one 6-O-sulfamates, a new class of potent steroid sulfatase (STS) inhibitors, were evaluated for their estrogenic potential. Structure-activity relationships for estrogenic activity were identified; however, no correlation with STS inhibition was found. Estrogenicity is favored by bulky side chains an...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm030926s

    authors： Nussbaumer P,Winiski AP,Billich A

    更新日期：2003-11-06 00:00:00

  • Quantitative structure-activity relationships of 6-anilinouracils as inhibitors of Bacillus subtilis DNA polymerase III.

    abstract：:Quantitative structure-activity relationships (QSAR) of a series of 6-anilinouracil derivatives were developed for their inhibitory activity against the wild-type DNA polymerase III (pol III) and a mutant enzyme, pol III/azp-12, derived from Bacillus subtilis. Interaction between inhibitors and both enzymes appears to...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00368a013

    authors： Wright GE,Gambino JJ

    更新日期：1984-02-01 00:00:00

  • Analgetic and antiinflammatory 7-aroylbenzofuran-5-ylacetic acids and 7-aroylbenzothiophene-5-ylacetic acids.

    abstract：:A number of 7-benzoylbenzofuran-5-ylacetic acids and 7-benzoylbenzothiophene-5-ylacetic acids were synthesized. The compounds were generally only 1/2 to 3 times as potent as phenylbutazone in the rat paw edema antiinflammatory assay. However, they show greater activity as analgetic agents. The most active compound is ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00161a030

    authors： Dunn JP,Ackerman NA,Tomolonis AJ

    更新日期：1986-11-01 00:00:00

  • Development and validation of k-nearest-neighbor QSPR models of metabolic stability of drug candidates.

    abstract：:Computational ADME (absorption, distribution, metabolism, and excretion) models may be used early in the drug discovery process in order to flag drug candidates with potentially problematic ADME profiles. We report the development, validation, and application of quantitative structure-property relationship (QSPR) mode...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm020491t

    authors： Shen M,Xiao Y,Golbraikh A,Gombar VK,Tropsha A

    更新日期：2003-07-03 00:00:00

  • Quantitative analyses of aggregation, autofluorescence, and reactivity artifacts in a screen for inhibitors of a thiol protease.

    abstract：:The perceived and actual burden of false positives in high-throughput screening has received considerable attention; however, few studies exist on the contributions of distinct mechanisms of nonspecific effects like chemical reactivity, assay signal interference, and colloidal aggregation. Here, we analyze the outcome...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm901070c

    authors： Jadhav A,Ferreira RS,Klumpp C,Mott BT,Austin CP,Inglese J,Thomas CJ,Maloney DJ,Shoichet BK,Simeonov A

    更新日期：2010-01-14 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

    doi：10.1021/jm00368a021

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

    更新日期：1984-02-01 00:00:00

  • Metal complexes of mitomycins.

    abstract：:The preparation of stable complexes between the N7-[2-(2-pyridyl)ethyl] and N7-(2-piperazinylethyl) derivatives of mitomycin C and metal ions such as Cu(II), Zn(II), and Pt(II) was accomplished. Mitomycin C did not form stable complexes, but it rearranged to a mitosene capable of complex formation. Some of these compl...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00151a023

    authors： Iyengar BS,Takahashi T,Remers WA,Bradner WT

    更新日期：1986-01-01 00:00:00

  • Dicarba analogues of the cyclic enkephalin peptides H-Tyr-c[D-Cys-Gly-Phe-D(or L)-Cys]NH(2) retain high opioid activity.

    abstract：:Dicarba analogues of the cyclic opioid peptides H-Tyr-c[d-Cys-Gly-Phe-d(or l)-Cys]NH2 were synthesized on solid phase by substituting allylglycines for the cysteines and cyclization by ring-closing metathesis between the side chains of the allylglycine residues. Mixtures of cis and trans isomers of the resulting olefi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm061294n

    authors： Berezowska I,Chung NN,Lemieux C,Wilkes BC,Schiller PW

    更新日期：2007-03-22 00:00:00

  • High-affinity, non-peptide agonists for the ORL1 (orphanin FQ/nociceptin) receptor.

    abstract：:The discovery of 8-(5,8-dichloro-1,2,3,4-tetrahydro-naphthalen-2-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one, 1a, as a high-affinity ligand for the human ORL1 (orphanin FQ/nociceptin) receptor led to the synthesis of a series of optimized ligands. These compounds exhibit high affinity for the human ORL1 receptor, e...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm991129q

    authors： Röver S,Adam G,Cesura AM,Galley G,Jenck F,Monsma FJ Jr,Wichmann J,Dautzenberg FM

    更新日期：2000-04-06 00:00:00

  • Conformationally constrained analogues of diacylglycerol. 13. Protein kinase C ligands based on templates derived from 2,3-dideoxy-L-erythro(threo)-hexono-1,4-lactone and 2-deoxyapiolactone.

    abstract：:In the present investigation, the last two possible modes of generating conformationally semirigid diacylglycerol (DAG) analogues embedded into five-membered ring lactones as templates III and IV are investigated. The first two templates studied in previous investigations corresponded to 2-deoxyribonolactone (template...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm960525v

    authors： Lee J,Lewin NE,Acs P,Blumberg PM,Marquez VE

    更新日期：1996-12-06 00:00:00

  • A marked change of receptor affinity of the 2-methyl-5-(3-hydroxyphenyl)morphans upon attachment of an (E)-8-benzylidene moiety: synthesis and evaluation of a new class of sigma receptor ligands.

    abstract：:The (E)-8-benzylidene and (E)-8-(3,4-dichlorobenzylidene), 7-ketone derivatives, 5 and 6, of the synthetic opiate 2-methyl-5-(3-hydroxyphenyl)morphan [5-(3-hydroxyphenyl)-2-methyl-2-azabicyclo[3.3.1]nonane, 1], were synthesized from the 7-ketone derivatives 2 or 4 via the Claisen-Schmidt reaction. The corresponding en...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00045a022

    authors： Bertha CM,Mattson MV,Flippen-Anderson JL,Rothman RB,Xu H,Cha XY,Becketts K,Rice KC

    更新日期：1994-09-16 00:00:00

  • Design and synthesis of pyrrolidine-5,5-trans-lactams (5-oxo-hexahydro-pyrrolo[3,2-b]pyrroles) as novel mechanism-based inhibitors of human cytomegalovirus protease. 1. The alpha-methyl-trans-lactam template.

    abstract：:Mechanism-based inhibitors of human cytomegalovirus (HCMV) protease have been designed based on the pyrrolidine-5,5-trans-lactam ring system. New routes to the beta-methyl-, desmethyl-, and alpha-methyl-pyrrolidine-5,5-trans-lactam templates have been developed from 2,4-diaminobutyric acid. ESI/MS studies have shown t...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm000078q

    authors： Borthwick AD,Angier SJ,Crame AJ,Exall AM,Haley TM,Hart GJ,Mason AM,Pennell AM,Weingarten GG

    更新日期：2000-11-16 00:00:00

  • Discovery of potent, highly selective, and orally bioavailable pyridine carboxamide c-Jun NH2-terminal kinase inhibitors.

    abstract：:C-Jun NH2 terminal kinases (JNKs) are important cell signaling enzymes. JNK1 plays a central role in linking obesity and insulin resistance. JNK2 and JNK3 may be involved in inflammatory and neurological disorders, respectively. Small-molecule JNK inhibitors could be valuable tools to study the therapeutic benefits of...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm060465l

    authors： Zhao H,Serby MD,Xin Z,Szczepankiewicz BG,Liu M,Kosogof C,Liu B,Nelson LT,Johnson EF,Wang S,Pederson T,Gum RJ,Clampit JE,Haasch DL,Abad-Zapatero C,Fry EH,Rondinone C,Trevillyan JM,Sham HL,Liu G

    更新日期：2006-07-27 00:00:00

  • Docking of flexible molecules using multiscale ligand representations.

    abstract：:Structural genomics will yield an immense number of protein three-dimensional structures in the near future. Automated theoretical methodologies are needed to exploit this information and are likely to play a pivotal role in drug discovery. Here, we present a fully automated, efficient docking methodology that does no...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm020830i

    authors： Glick M,Grant GH,Richards WG

    更新日期：2002-10-10 00:00:00

  • GIP(Lys16PAL) and GIP(Lys37PAL): novel long-acting acylated analogues of glucose-dependent insulinotropic polypeptide with improved antidiabetic potential.

    abstract：:Glucose-dependent insulinotropic polypeptide (GIP) is a physiological insulin releasing peptide. We have developed two novel fatty acid derivatized GIP analogues, which bind to serum albumin and demonstrate enhanced duration of action in vivo. GIP(Lys(16)PAL) and GIP(Lys(37)PAL) were resistant to dipeptidyl peptidase ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0509997

    authors： Irwin N,O'Harte FP,Gault VA,Green BD,Greer B,Harriott P,Bailey CJ,Flatt PR

    更新日期：2006-02-09 00:00:00

  • Inhibition of human O6-alkylguanine-DNA alkyltransferase and potentiation of the cytotoxicity of chloroethylnitrosourea by 4(6)-(benzyloxy)-2,6(4)-diamino-5-(nitro or nitroso)pyrimidine derivatives and analogues.

    abstract：:A series of 4(6)-(benzyloxy)-2,6(4)-diamino-5-(nitro or nitroso)pyrimidine derivatives and analogues of which 4(6)-benzyloxy groups were replaced with a (2-, 3-, or 4-fluorobenzyl)oxy or (2-, 3-, or 4-pyridylmethyl)oxy group, was synthesized. The abilities of these compounds to inhibit human O6-alkylguanine-DNA alkylt...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm970363i

    authors： Terashima I,Kohda K

    更新日期：1998-02-12 00:00:00