当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > A simple method for predicting serum protein binding of compounds from IC(50) shift analysis for in vitro assays.

A simple method for predicting serum protein binding of compounds from IC(50) shift analysis for in vitro assays.

Abstract：

:The shift in apparent IC(50) that attends addition of serum proteins to in vitro cellular, enzymatic, and receptor binding assays can be used to determine the dissociation constant for compound-serum protein complexes. We show here that a simple linear relationship exists between the apparent IC(50) in the presence of serum protein and the inverse of the apparent K(d) for the compound-serum protein complex. Using a series of cell-active kinase inhibitors we demonstrate that the K(d) value derived in this way can be used to predict the extent of protein binding in serum for various compounds. This method should provide a simple means of assessing the relative serum protein binding propensity of compounds early in the compound optimization phase of drug discovery campaigns.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Rusnak DW,Lai Z,Lansing TJ,Rhodes N,Gilmer TM,Copeland RA

doi

10.1016/j.bmcl.2004.01.103

subject

Has Abstract

pub_date

2004-05-03 00:00:00

pages

2309-12

issue

9

eissn

0960-894X

issn

1464-3405

pii

S0960894X04001787

journal_volume

14

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Identification of a novel oxidation product from yellow fluorophore in the complex of apoPholasin and dehydrocoelenterazine.

    abstract：:The complex of the recombinant fusion protein of apoPholasin and glutathione S-transferase (GST-apoPholasin) with non-fluorescent dehydrocoelenterazine (dCTZ) (GST-apoPholasin/dCTZ complex) shows yellow fluorescence at 539 nm by excitation at 430 nm. The GST-apoPholasin/dCTZ complex with a fluorophore (dCTZ*) has cons...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127435

    authors： Inouye S,Nakamura M,Taguchi J,Hosoya T

    更新日期：2020-10-01 00:00:00

  • In vitro selection of a 3' terminal short protector that stabilizes transcripts to improve the translation efficiency in a wheat germ extract.

    abstract：:Wheat cell-free expression systems based on wheat germ extract (WGE) enable us to briefly synthesize various types of proteins in vitro merely by exogenously adding their mRNA templates. Moreover, it is possible to produce larger amounts of protein by thoroughly removing the endosperm, which contains many translation ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 信件

    doi：10.1016/j.bmcl.2019.06.058

    authors： Ogawa A,Kutsuna A,Takamatsu M,Okuzono T

    更新日期：2019-08-15 00:00:00

  • Investigation of the PDZ domain ligand binding site using chemically modified peptides.

    abstract：:Several chemically modified analogues to a tightly binding ligand for the second PDZ domain of MAGI-3 were synthesized and evaluated for their ability to compete with native peptide ligands. N-methyl scanning of the ligand backbone amides revealed the energetically important hydrogen bonds between the ligand backbone ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00345-1

    authors： Novak KA,Fujii N,Guy RK

    更新日期：2002-09-02 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

  • Schiff's bases of quinazolinone derivatives: Synthesis and SAR studies of a novel series of potential anti-inflammatory and antioxidants.

    abstract：:A series of quinazolinone derived Schiff base derivatives 7-28 were synthesized and characterized as novel antioxidants and anti-inflammatory agents. The in vitro antioxidant activities of these compounds were evaluated and compared with commercial antioxidants ascorbic acid (AA), gallic acid (GA), butylatedhydroxytol...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmcl.2015.01.010

    authors： Rakesh KP,Manukumar HM,Gowda DC

    更新日期：2015-03-01 00:00:00

  • Urokinase-type plasminogen activator expression and Rac1/WAVE-2/Arp2/3 pathway are blocked by pterostilbene to suppress cell migration and invasion in MDA-MB-231 cells.

    abstract：:Breast cancer is the most common malignancy among females, and cancer invasion and metastasis are the leading causes of cancer death in breast cancer patients. Pterostilbene, a naturally occurring dimethylether analogue of resveratrol, has been demonstrated to possess anti-cancer effects. However, inhibitory effects o...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.12.115

    authors： Ko HS,Kim JS,Cho SM,Lee HJ,Ahn KS,Kim SH,Lee EO

    更新日期：2014-02-15 00:00:00

  • Derivatization of the C12-C13 functional groups of epothilones A, B and C.

    abstract：:Epothilone A reacted with hydrohalic acids to C12-C13 halohydrin regioisomers (ratios: 2:1-4:1), whereas epothilone B gave under the same conditions the isomerically pure C12 halo C13 hydroxy derivative. With non-nucleophilic Brønstedt acids and with Lewis acids a highly solvent dependent product distribution and some...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/S0960-894X(98)00546-0

    authors： Sefkow M,Kiffe M,Höfle G

    更新日期：1998-11-03 00:00:00

  • Evaluation of nitroalkenes as nitric oxide donors.

    abstract：:Chemiluminescence experiments demonstrate that simple nitroalkenes release low levels of nitric oxide. UV and EPR measurements suggest but cannot confirm direct NO release from nitroalkenes. Given the biological activity of nitrated unsaturated fatty acids, these results suggest the possible metabolic conversion of ni...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.01.016

    authors： Gorczynski MJ,Huang J,Lee H,King SB

    更新日期：2007-04-01 00:00:00

  • Expanding the chemical space of human serine racemase inhibitors.

    abstract：:Serine racemase, the enzyme responsible for d-serine synthesis in the central nervous system, has been identified as a potential therapeutic target to treat N-methyl-d-aspartate receptors-related pathologies. The search for specific inhibitors of the enzyme has revealed that serine racemase is a difficult target, with...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.07.081

    authors： Dellafiora L,Marchetti M,Spyrakis F,Orlandi V,Campanini B,Cruciani G,Cozzini P,Mozzarelli A

    更新日期：2015-10-01 00:00:00

  • Chemical synthesis of S-ribosyl-L-homocysteine and activity assay as a LuxS substrate.

    abstract：:Bacterial quorum sensing is mediated by autoinducers, small signaling molecules generated by bacteria. It has been proposed that the LuxS enzyme converts S-ribosyl-L-homocysteine to 4,5-dihydroxy-2,3-pentanedione, the precursor of autoinducer 2 (AI-2). We report here a chemical synthesis of S-ribosyl-L-homocysteine an...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.09.015

    authors： Zhao G,Wan W,Mansouri S,Alfaro JF,Bassler BL,Cornell KA,Zhou ZS

    更新日期：2003-11-17 00:00:00

  • "Propylene spaced" allyl tin reagents: a new class of fluorous tin reagents for allylations under radical and metal-catalyzed conditions.

    abstract：:A new generation of propylene-spaced fluorous allyltin reagents [(Rf(CH2)3)3SnCH2CH = CH2] is described. These succeed in radical allylations where their lower homologs (ethylene-spaced) fail, and they provide improved performance in transition metal catalyzed allylations. The reagents and byproducts are readily separ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00435-1

    authors： Curran DP,Luo Z,Degenkolb P

    更新日期：1998-09-08 00:00:00

  • From benzimidazole to indole-5-carboxamide Thumb Pocket I inhibitors of HCV NS5B polymerase. Part 1: indole C-2 SAR and discovery of diamide derivatives with nanomolar potency in cell-based subgenomic replicons.

    abstract：:Replacement of the benzimidazole core of allosteric Thumb Pocket 1 HCV NS5B finger loop inhibitors by more lipophilic indole derivatives provided up to 30-fold potency improvements in cell-based subgenomic replicon assays. Optimization of C-2 substitution on the indole core led to the identification of analogs with EC...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.04.059

    authors： Beaulieu PL,Gillard J,Jolicoeur E,Duan J,Garneau M,Kukolj G,Poupart MA

    更新日期：2011-06-15 00:00:00

  • Novel non-benzimidazole chk2 kinase inhibitors.

    abstract：:In a recent paper, [Arienti, K. L.; Brunmark, A.; Axe, F. U.; McClure, K. M.; Lee, A.; Blevitt, J.; Neff, D. K.; Huang, L.; Crawford, S.; Chennagiri, R. P.; Karlsson, L.; Brietenbucher, J. G. J. Med. Chem.2005, 48, 1873], we described the discovery of a class of benzimidazole chk2 kinase inhibitors, exemplified by com...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.12.096

    authors： McClure KJ,Huang L,Arienti KL,Axe FU,Brunmark A,Blevitt J,Breitenbucher JG

    更新日期：2006-04-01 00:00:00

  • Gastric-sparing nitric oxide-releasable 'true' prodrugs of aspirin and naproxen.

    abstract：:Nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are gaining attention as potentially gastric-sparing NSAIDs. Herein, we report a novel class of '1-(nitrooxy)ethyl ester' group-containing NSAIDS as efficient NO releasing 'true' prodrugs of aspirin and naproxen. While an aspirin prodrug exhibite...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.10.096

    authors： Gund M,Gaikwad P,Borhade N,Burhan A,Desai DC,Sharma A,Dhiman M,Patil M,Sheikh J,Thakre G,Tipparam SG,Sharma S,Nemmani KVS,Satyam A

    更新日期：2014-12-15 00:00:00

  • Synthesis of novel keto-ACE analogues as domain-selective angiotensin I-converting enzyme inhibitors.

    abstract：:Novel analogues of the angiotensin I-converting enzyme (ACE) inhibitor keto-ACE were synthesized via a facile Horner-Emmons olefination of a phosphonoketone precursor with ethyl glyoxylate. Introduction of a bulky aromatic tryptophan at the P(2)(') position of keto-ACE resulted in a significant increase in C-domain-se...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.06.003

    authors： Nchinda AT,Chibale K,Redelinghuys P,Sturrock ED

    更新日期：2006-09-01 00:00:00

  • Structure based medicinal chemistry approach to develop 4-methyl-7-deazaadenine carbocyclic nucleosides as anti-HCV agent.

    abstract：:The structure-based approaches were implemented to design and rationally select the molecules for synthesis and anti-HCV activity evaluation. The systematic structure-activity relationships of previously discovered molecules (types I, II, III) were analyzed to design new molecules (type IV) by bioisosteric replacement...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.09.072

    authors： Thiyagarajan A,Salim MT,Balaraju T,Bal C,Baba M,Sharon A

    更新日期：2012-12-15 00:00:00

  • Phosphodiesterase inhibitors. Part 1: Synthesis and structure-activity relationships of pyrazolopyridine-pyridazinone PDE inhibitors developed from ibudilast.

    abstract：:Ibudilast [1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)-2-methylpropan-1-one] is a nonselective phosphodiesterase inhibitor used clinically to treat asthma. Efforts to selectively develop the PDE3- and PDE4-inhibitory activity of ibudilast led to replacement of the isopropyl ketone by a pyridazinone heterocycle. Structu...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.04.021

    authors： Allcock RW,Blakli H,Jiang Z,Johnston KA,Morgan KM,Rosair GM,Iwase K,Kohno Y,Adams DR

    更新日期：2011-06-01 00:00:00

  • The discovery and unique pharmacological profile of RO4938581 and RO4882224 as potent and selective GABAA alpha5 inverse agonists for the treatment of cognitive dysfunction.

    abstract：:Lead optimisation of the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine class led to the identification of two clinical leads [RO4882224 (11) and RO4938581 (44)] functioning as novel potent and selective GABAA alpha5 inverse agonists. The unique pharmacological profiles and optimal pharmacokinetic profiles r...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.08.053

    authors： Knust H,Achermann G,Ballard T,Buettelmann B,Gasser R,Fischer H,Hernandez MC,Knoflach F,Koblet A,Stadler H,Thomas AW,Trube G,Waldmeier P

    更新日期：2009-10-15 00:00:00

  • Molecular modeling aided design of nicotinic acid receptor GPR109A agonists.

    abstract：:A homology model of the nicotinic acid receptor GPR109A was constructed based on the X-ray crystal structure of bovine rhodopsin. An HTS hit was docked into the homology model. Characterization of the binding pocket by a grid-based surface calculation of the docking model suggested that a larger hydrophobic body plus ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.08.030

    authors： Deng Q,Frie JL,Marley DM,Beresis RT,Ren N,Cai TQ,Taggart AK,Cheng K,Carballo-Jane E,Wang J,Tong X,Waters MG,Tata JR,Colletti SL

    更新日期：2008-09-15 00:00:00

  • Discovery of potent, selective small molecule inhibitors of α-subtype of type III phosphatidylinositol-4-kinase (PI4KIIIα).

    abstract：:The discovery and optimisation of novel, potent and selective small molecule inhibitors of the α-isoform of type III phosphatidylinositol-4-kinase (PI4Kα) are described. Lead compounds show cellular activity consistent with their PI4Kα potency inhibiting the accumulation of IP1 after PDGF stimulation and reducing cell...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.05.093

    authors： Raubo P,Andrews DM,McKelvie JC,Robb GR,Smith JM,Swarbrick ME,Waring MJ

    更新日期：2015-08-15 00:00:00

  • Discovery of (E)-5-(benzylideneamino)-1H-benzo[d]imidazol-2(3H)-one derivatives as inhibitors for PTK6.

    abstract：:A lead compound 1, which inhibits the catalytic activity of PTK6, was selected from a chemical library. Derivatives of compound 1 were synthesized and analyzed for inhibitory activity against PTK6 in vitro and at the cellular level. Selected compounds were analyzed for cytotoxicity in human foreskin fibroblasts using ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.08.036

    authors： Shim HJ,Yang HR,Kim HI,Kang SA,No KT,Jung YH,Lee ST

    更新日期：2014-10-01 00:00:00

  • Poly(styrene-alt-maleic anhydride) derivatives as potent anti-HIV microbicide candidates.

    abstract：:Topical microbicides offer women the opportunity to protect themselves from sexual HIV transmission under their own control. A series of poly[styrene-alt-(maleic anhydride)] derivatives were prepared by amidation or hydrolysis of the anhydride moiety. The derivatives were shown to be of low cell toxicity and effective...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.02.059

    authors： Fang W,Cai Y,Chen X,Su R,Chen T,Xia N,Li L,Yang Q,Han J,Han S

    更新日期：2009-04-01 00:00:00

  • Sesterterpene sulfates as isocitrate lyase inhibitors from tropical sponge Hippospongia sp.

    abstract：:Two sesterterpene sulfates (1-2) were isolated from tropical sponge Hippospongia sp. and their inhibitory activities against isocitrate lyase (ICL) from the rice blast fungus Mgnaporthe grisea were evaluated. Compound 3 was obtained by hydrolysis of compound 1. Compounds 1 and 3 were found to be potent ICL inhibitors,...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.02.027

    authors： Lee HS,Lee TH,Yang SH,Shin HJ,Shin J,Oh KB

    更新日期：2007-05-01 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

  • Synthesis of 2-methyl-1,4-naphthoquinones with higher gamma-glutamyl carboxylase activity than MK-4 both in vitro and in vivo.

    abstract：:Vitamin K is the collective term for compounds that share a 2-methyl-1,4-naphthoquinone ring, but differ in the side-chain at the 3-position. We synthesized novel 2-methyl-1,4-naphthoquinone derivatives with different side chain length at the 3-position. Derivatives with C-14 and C-16 tails showed the highest in vitro...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.11.073

    authors： Vermeer C,van 't Hoofd C,Knapen MHJ,Xanthoulea S

    更新日期：2017-01-15 00:00:00

  • Parallel solid-phase synthesis of a model library of 7alpha-alkylamide estradiol derivatives as potential estrogen receptor antagonists.

    abstract：:The C17-THP derivative of 7alpha-(11-azidoundecanyl)-estradiol (4) was synthesized and coupled to an aminomethyl resin via a photolabile o-nitrobenzyl linker. Reduction of the azide by the Staudinger reaction to its corresponding amine followed by acylation using four activated NFmoc protected amino acids gave a first...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00487-4

    authors： Tremblay MR,Simard J,Poirier D

    更新日期：1999-10-04 00:00:00

  • Synthesis and biological evaluation of substituted benzoxazoles as inhibitors of mPGES-1: use of a conformation-based hypothesis to facilitate compound design.

    abstract：:Microsomal prostaglandin E(2) synthase-1 (mPGES-1) is a novel therapeutic target for the treatment of inflammation and pain. In the preceding letter, we detailed the discovery of clinical candidate PF-04693627, a potent mPGES-1 inhibitor possessing a novel benzoxazole structure. While PF-04693627 was undergoing furthe...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.11.107

    authors： Walker DP,Arhancet GB,Lu HF,Heasley SE,Metz S,Kablaoui NM,Franco FM,Hanau CE,Scholten JA,Springer JR,Fobian YM,Carter JS,Xing L,Yang S,Shaffer AF,Jerome GM,Baratta MT,Moore WM,Vazquez ML

    更新日期：2013-02-15 00:00:00

  • Novel bis(indolyl)hydrazide-hydrazones as potent cytotoxic agents.

    abstract：:A series of bis(indolyl) hydrazide-hydrazones 5a-n were synthesized and evaluated for their cytotoxicity against selected human cancer cell lines. The reaction of indole-3-carboxaldehyde 2 with indole-3-carbohydrazide 4 in presence of catalytic amount of acetic acid afforded 5a-n in good yields. Among the synthesized ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.11.031

    authors： Kumar D,Maruthi Kumar N,Ghosh S,Shah K

    更新日期：2012-01-01 00:00:00

  • Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 4: synthesis and structure-activity relationships for 1-[N-(methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-(4-(N-(alkyl)-N-(benzyloxycarbonyl)amino)piperidin-1-yl)butanes.

    abstract：:(2S)-2-(3-Chlorophenyl)-1-[N-(methyl)-N-(phenylsulfonyl)amino]-4-[spiro(2,3-dihydrobenzthiophene-3,4'-piperidin-1'-yl)]butane S-oxide (1b) has been identified as a potent CCR5 antagonist having an IC50=10 nM. Herein, structure-activity relationship studies of non-spiro piperidines are described, which led to the disco...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00492-9

    authors： Finke PE,Oates B,Mills SG,MacCoss M,Malkowitz L,Springer MS,Gould SL,DeMartino JA,Carella A,Carver G,Holmes K,Danzeisen R,Hazuda D,Kessler J,Lineberger J,Miller M,Schleif WA,Emini EA

    更新日期：2001-09-17 00:00:00

  • A unidirectional crosslinking strategy for HIV-1 protease dimerization inhibitors.

    abstract：:A novel strategy to identify potent HIV-1 protease dimerization inhibitors was developed using 12-aminododecanoic acid as a tether to crosslink interfacial peptides. The directionality of the southern peptide was changed from N-->C to C-->N as compared to previously reported inhibitors. The terminal amine of the south...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.05.081

    authors： Hwang YS,Chmielewski J

    更新日期：2004-08-16 00:00:00