当前位置： SCI文献检索 > ACS Medicinal Chemistry Letters期刊下所有文献 > Structure-Guided Rescaffolding of Selective Antagonists of BCL-XL.

Structure-Guided Rescaffolding of Selective Antagonists of BCL-XL.

Abstract：

:Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-XL antagonists containing an undesirable hydrazone functionality, in silico design and X-ray crystallography were utilized to develop alternative scaffolds that retained the selectivity and potency of the starting compounds.

journal_name

ACS Med Chem Lett

journal_title

ACS medicinal chemistry letters

authors

Koehler MF,Bergeron P,Choo EF,Lau K,Ndubaku C,Dudley D,Gibbons P,Sleebs BE,Rye CS,Nikolakopoulos G,Bui C,Kulasegaram S,Kersten WJ,Smith BJ,Czabotar PE,Colman PM,Huang DC,Baell JB,Watson KG,Hasvold L,Tao ZF,Wang

doi

10.1021/ml500030p

subject

Has Abstract

pub_date

2014-03-21 00:00:00

pages

662-7

issue

6

issn

1948-5875

journal_volume

5

pub_type

杂志文章

相关文献

ACS Medicinal Chemistry Letters文献大全
  • N-Methylated sst2 Selective Somatostatin Cyclic Peptide Analogue as a Potent Candidate for Treating Neurogenic Inflammation.

    abstract：:A focused multiply N-methylated library of a cyclic hexapeptidic somatostatin analogue: MK678 cyclo(-MeAYwKVF-) was generated, which resulted in the unexpected observation of an efficacious tetra-N-methylated analogue, cyclo(-MeAYMewMeKVMeF-) with a potent inhibitory action on sensory neuropeptide release in vitro and...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/ml200032v

    authors： Chatterjee J,Laufer B,Beck JG,Helyes Z,Pintér E,Szolcsányi J,Horvath A,Mandl J,Reubi JC,Kéri G,Kessler H

    更新日期：2011-04-04 00:00:00

  • Spotlight on fluorescent biosensors-tools for diagnostics and drug discovery.

    abstract：:Fluorescent biosensors constitute potent tools for probing biomolecules in their natural environment and for visualizing dynamic processes in complex biological samples, living cells, and organisms. They are well suited for highlighting molecular alterations associated with pathological disorders, thereby offering mea...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/ml400472e

    authors： Morris MC

    更新日期：2013-12-18 00:00:00

  • Discovery and Biological Evaluation of Novel Dual EGFR/c-Met Inhibitors.

    abstract：:Activating mutations in the epidermal growth factor receptor (EGFR) have been identified in a subset of non-small cell lung cancer (NSCLC), which is one of the leading cancer types worldwide. Application of EGFR tyrosine kinase inhibitors leads to acquired resistance by secondary EGFR mutations or by amplification of ...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/ml4003309

    authors： Szokol B,Gyulavári P,Kurkó I,Baska F,Szántai-Kis C,Greff Z,Orfi Z,Peták I,Pénzes K,Torka R,Ullrich A,Orfi L,Vántus T,Kéri G

    更新日期：2014-01-30 00:00:00

  • Discovery of a Type III Inhibitor of LIM Kinase 2 That Binds in a DFG-Out Conformation.

    abstract：:The first allosteric, type III inhibitor of LIM-kinase 2 (LIMK2) is reported. A series of molecules that feature both an N-phenylsulfonamide and tertiary amide were not only very potent at LIMK2 but also were extremely selective against a panel of other kinases. Enzymatic kinetic studies showed these molecules to be n...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/ml500242y

    authors： Goodwin NC,Cianchetta G,Burgoon HA,Healy J,Mabon R,Strobel ED,Allen J,Wang S,Hamman BD,Rawlins DB

    更新日期：2014-08-07 00:00:00

  • Synthesis and Structure-Activity Relationship of Pyxinol Derivatives as Novel Anti-Inflammatory Agents.

    abstract：:Pyxinol, the main metabolite of 20S-protopanaxadiol in human liver, was chosen as a novel skeleton for the development of anti-inflammatory agents. Pyxinol derivatives modified at C-3, C-12, or C-25 and selected stereoisomers were designed, prepared, and investigated for in vitro anti-inflammatory activities. Structur...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.9b00562

    authors： Sun Y,Fang X,Gao M,Wang C,Gao H,Bi W,Tang H,Cui Y,Zhang L,Fan H,Yu H,Yang G

    更新日期：2020-02-12 00:00:00

  • Synthesis, Biological Evaluation, and Autophagy Mechanism of 12N-Substituted Sophoridinamines as Novel Anticancer Agents.

    abstract：:A series of 12N-substituted sophoridinamine derivatives were synthesized and evaluated for their cytotoxic activities in human HepG2 hepatoma cells. Structure-activity relationship revealed that introduction of a suitable arylidene or arylethyl at the N'-end could greatly enhance antiproliferation potency. Among them,...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.6b00466

    authors： Bi C,Zhang N,Yang P,Ye C,Wang Y,Fan T,Shao R,Deng H,Song D

    更新日期：2017-01-05 00:00:00

  • Structural Approach to Assessing the Innovativeness of New Drugs Finds Accelerating Rate of Innovation.

    abstract：:Measuring innovation in the pharmaceutical industry is challenging. Counts of new molecular entities (NMEs) approved by the Food and Drug Administration (FDA) are commonly used, but this measure only gauges quantity not innovativeness. A new indicator of innovation for small molecule and peptide drugs based on structu...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.0c00319

    authors： Wills TJ,Lipkus AH

    更新日期：2020-09-10 00:00:00

  • Amino Acid Thioester Derivatives: A Highly Promising Scaffold for the Development of Metallo-β-lactamase L1 Inhibitors.

    abstract：:In light of the biomedical significance of metallo-β-lactamases (MβLs), ten new mercaptoacetic acid thioester amino acid derivatives were synthesized and characterized. Biological activity assays indicated that all these synthesized compounds are very potent inhibitors of L1, exhibiting an IC50 value range of 0.018-2....

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.5b00098

    authors： Liu XL,Shi Y,Kang JS,Oelschlaeger P,Yang KW

    更新日期：2015-04-23 00:00:00

  • Multicomponent Synthesis and Biological Evaluation of a Piperazine-Based Dopamine Receptor Ligand Library.

    abstract：:A series of 1,4-disubstituted piperazine-based compounds were designed, synthesized, and evaluated as dopamine D2/D3 receptor ligands. The synthesis relies on the key multicomponent split-Ugi reaction, assessing its great potential in generating chemical diversity around the piperazine core. With the aim of evaluating...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.5b00131

    authors： Stucchi M,Gmeiner P,Huebner H,Rainoldi G,Sacchetti A,Silvani A,Lesma G

    更新日期：2015-06-23 00:00:00

  • Structure-Guided Optimization of Replication Protein A (RPA)-DNA Interaction Inhibitors.

    abstract：:Replication protein A (RPA) is the major human single stranded DNA (ssDNA)-binding protein, playing essential roles in DNA replication, repair, recombination, and DNA-damage response (DDR). Inhibition of RPA-DNA interactions represents a therapeutic strategy for cancer drug discovery and has great potential to provide...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.9b00440

    authors： Gavande NS,VanderVere-Carozza PS,Pawelczak KS,Vernon TL,Jordan MR,Turchi JJ

    更新日期：2020-01-02 00:00:00

  • 3-Amino-chromanes and Tetrahydroquinolines as Selective 5-HT2B, 5-HT7, or σ1 Receptor Ligands.

    abstract：:The phenethylamine backbone is a privileged substructure found in a wide variety of G protein-coupled receptor (GPCR) ligands. This includes both endogenous neurotransmitters and active pharmaceutical agents. More than 20 structurally unique heterocyclic phenethylamine derivatives were broadly evaluated for GPCR affin...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.9b00225

    authors： Porter MR,Xiao H,Wang J,Smith SB,Topczewski JJ

    更新日期：2019-09-23 00:00:00

  • Discovery of a potent thiadiazole class of histamine h3 receptor antagonist for the treatment of diabetes.

    abstract：:A series of novel 2-piperidinopiperidine thiadiazoles were synthesized and evaluated as new leads of histamine H3 receptor antagonists. The 4-(5-([1,4'-bipiperidin]-1'-yl)-1,3,4-thiadiazol-2-yl)-2-(pyridin-2-yl)morpholine (5u) displayed excellent potency and ex vivo receptor occupancy. Compound 5u was also evaluated i...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/ml200250t

    authors： Rao AU,Shao N,Aslanian RG,Chan TY,Degrado SJ,Wang L,McKittrick B,Senior M,West RE Jr,Williams SM,Wu RL,Hwa J,Patel B,Zheng S,Sondey C,Palani A

    更新日期：2011-11-21 00:00:00

  • Identification of a Novel and Selective Series of Itk Inhibitors via a Template-Hopping Strategy.

    abstract：:Inhibition of Itk potentially constitutes a novel, nonsteroidal treatment for asthma and other T-cell mediated diseases. In-house kinase cross-screening resulted in the identification of an aminopyrazole-based series of Itk inhibitors. Initial work on this series highlighted selectivity issues with several other kinas...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/ml400206q

    authors： Alder CM,Ambler M,Campbell AJ,Champigny AC,Deakin AM,Harling JD,Harris CA,Longstaff T,Lynn S,Maxwell AC,Mooney CJ,Scullion C,Singh OM,Smith IE,Somers DO,Tame CJ,Wayne G,Wilson C,Woolven JM

    更新日期：2013-08-12 00:00:00

  • A Medicinal Chemist's Perspective on Transitioning from Industry to Academic Drug Discovery.

    abstract：:Medicinal chemists have increasing opportunities to transition from the pharmaceutical industry to academic medical centers interested in translational research. This Viewpoint highlights some of the differences between these two cultures and strategies to succeed in academic drug discovery. ...

    journal_title：ACS medicinal chemistry letters

    pub_type： 社论

    doi：10.1021/acsmedchemlett.9b00107

    authors： Barrow JC

    更新日期：2019-04-15 00:00:00

  • Antimalarial and Structural Studies of Pyridine-containing Inhibitors of 1-Deoxyxylulose-5-phosphate Reductoisomerase.

    abstract：:1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate isoprene biosynthesis pathway is a target for developing antimalarial drugs. Fosmidomycin, a potent DXR inhibitor, showed safety as well as efficacy against P. falciparum malaria in clinical trials. Based on our previous quantitative structure...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/ml300419r

    authors： Xue J,Diao J,Cai G,Deng L,Zheng B,Yao Y,Song Y

    更新日期：2013-02-14 00:00:00

  • What Do You Get from DNA-Encoded Libraries?

    abstract：:Use of DNA-encoded libraries (DELs) in the pharmaceutical industry has rapidly increased. We discuss what to expect when you run a DEL screen and contemplate guidelines for library design. Additionally, we consider some visionary work and extrapolate to the future. ...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.8b00128

    authors： Satz AL

    更新日期：2018-04-17 00:00:00

  • Photodynamic Activities of Porphyrin Derivative-Cyclodextrin Complexes by Photoirradiation.

    abstract：:Water-soluble cyclodextrin (CyD) complexed with porphyrin derivatives with different substituents in the meso-positions showed different photodynamic activities toward cancer cells under illumination at wavelengths over 600 nm, the most suitable wavelengths for photodynamic therapy (PDT). In particular, aniline- and p...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.7b00098

    authors： Ikeda A,Satake S,Mae T,Ueda M,Sugikawa K,Shigeto H,Funabashi H,Kuroda A

    更新日期：2017-04-19 00:00:00

  • Discovery and Pharmacological Characterization of Novel Quinazoline-Based PI3K Delta-Selective Inhibitors.

    abstract：:Inhibition of the lipid kinase PI3Kδ is a promising principle to treat B and T cell driven inflammatory diseases. Using a scaffold deconstruction-reconstruction strategy, we identified 4-aryl quinazolines that were optimized into potent PI3Kδ isoform selective analogues with good pharmacokinetic properties. With compo...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.6b00119

    authors： Hoegenauer K,Soldermann N,Stauffer F,Furet P,Graveleau N,Smith AB,Hebach C,Hollingworth GJ,Lewis I,Gutmann S,Rummel G,Knapp M,Wolf RM,Blanz J,Feifel R,Burkhart C,Zécri F

    更新日期：2016-06-02 00:00:00

  • Deciphering Binding Interactions of IL-23R with HDX-MS: Mapping Protein and Macrocyclic Dodecapeptide Ligands.

    abstract：:Molecular characterization of the binding epitope of IL-23R and its cognate cytokine IL-23 is paramount to understand the role in autoimmune diseases and to support the discovery of new inhibitors of this protein-protein interaction. Our results revealed that HDX-MS was able to identify the binding epitope of IL-23R:I...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.8b00255

    authors： Sayago C,Gonzalez Valcarcel IC,Qian Y,Lee J,Alsina-Fernandez J,Fite NC,Carrillo JJ,Zhang FF,Chalmers MJ,Dodge JA,Broughton H,Espada A

    更新日期：2018-08-01 00:00:00

  • Enhancing Therapeutic Efficacy of Cisplatin by Blocking DNA Damage Repair.

    abstract：:Self-repair of nuclear DNA damage is the most known reason that leads to drug resistance of cancer tissue and limited therapeutic efficacy of anticancer drugs. Inhibition of protein phosphatase 2A (PP2A) would block DNA damage-induced defense of cancer cells to suppress DNA repair for enhanced cancer treatment. Here, ...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.6b00236

    authors： Cong Y,Wang L,Wang Z,He S,Zhou D,Jing X,Huang Y

    更新日期：2016-08-24 00:00:00

  • Transdermal Bioavailability in Rats of Lidocaine in the Forms of Ionic Liquids, Salts, and Deep Eutectic.

    abstract：:Tuning the bioavailability of lidocaine was explored by its incorporation into the ionic liquid lidocainium docusate ([Lid][Doc]) and the deep eutectic Lidocaine·Ibuprofen (Lid·Ibu) and comparing the transdermal absorption of these with the crystalline salt lidocainium chloride ([Lid]Cl). Each form of lidocaine was di...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.6b00504

    authors： Berton P,Di Bona KR,Yancey D,Rizvi SAA,Gray M,Gurau G,Shamshina JL,Rasco JF,Rogers RD

    更新日期：2017-04-12 00:00:00

  • Novel N-Substituted Benzomorphan-Based Compounds: From MOR-Agonist/DOR-Antagonist to Biased/Unbiased MOR Agonists.

    abstract：:Modifications at the basic nitrogen of the benzomorphan scaffold allowed the development of compounds able to segregate physiological responses downstream of the receptor signaling, opening new possibilities in opioid drug development. Alkylation of the phenyl ring in the N-substituent of the MOR-agonist/DOR-antagonis...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.9b00549

    authors： Pasquinucci L,Parenti C,Ruiz-Cantero MC,Georgoussi Z,Pallaki P,Cobos EJ,Amata E,Marrazzo A,Prezzavento O,Arena E,Dichiara M,Salerno L,Turnaturi R

    更新日期：2020-01-28 00:00:00

  • Rational Design of Cell-Active Inhibitors of PARP10.

    abstract：:Poly-ADP-ribose polymerases (PARPs 1-16) have emerged as major regulators of diverse cellular processes. PARPs can be subclassified based on their ability to catalyze poly-ADP-ribosylation (PARylation) or mono-ADP-ribosylation (MARylation). While much is known about the cellular roles of PARPs that catalyze PARylation...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.8b00429

    authors： Morgan RK,Kirby IT,Vermehren-Schmaedick A,Rodriguez K,Cohen MS

    更新日期：2018-11-29 00:00:00

  • Novel carboline derivatives as potent antifungal lead compounds: design, synthesis, and biological evaluation.

    abstract：:A series of novel antifungal carboline derivatives was designed and synthesized, which showed broad-spectrum antifungal activity. Particularly, compound C38 showed comparable in vitro antifungal activity to fluconazole without toxicity to human embryonic lung cells. It also exhibited good fungicidal activity against b...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/ml400492t

    authors： Wang S,Wang Y,Liu W,Liu N,Zhang Y,Dong G,Liu Y,Li Z,He X,Miao Z,Yao J,Li J,Zhang W,Sheng C

    更新日期：2014-02-13 00:00:00

  • A new challenging and promising era of tyrosine kinase inhibitors.

    abstract：:Protein kinases are key regulators that govern complex cellular processes. Dysregulation of kinase signaling is associated in many human diseases, particularly cancers and developmental and metabolic disorders. Tyrosine kinase inhibitors have achieved great success in molecular targeted therapies for cancer and now is...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/ml500091p

    authors： Cui JJ

    更新日期：2014-03-06 00:00:00

  • Identification of Human Toll-like Receptor 2-Agonistic Activity in Dihydropyridine-Quinolone Carboxamides.

    abstract：:Using a multiplexed, reporter gene-based, high-throughput screen, we identified 9-fluoro-7-hydroxy-3-methyl-5-oxo-N-(pyridin-3-ylmethyl)-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6-carboxamide as a TLR2 agonist. Preliminary structure-activity relationship studies on the carboxamide moiety led to the identification o...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.8b00540

    authors： Hu Z,Banothu J,Beesu M,Gustafson CJ,Brush MJH,Trautman KL,Salyer ACD,Pathakumari B,David SA

    更新日期：2018-12-20 00:00:00

  • Systematically Mitigating the p38α Activity of Triazole-based BET Inhibitors.

    abstract：:The Bromodomain and Extra Terminal (BET) family of proteins recognize post-translational N-ε-acetylated lysine modifications, regulating transcription as "reader" proteins. Bromodomain inhibitors are interesting targets for the development of potential cancer, inflammation, and heart disease treatments. Several dual k...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.9b00227

    authors： Carlson AS,Cui H,Divakaran A,Johnson JA,Brunner RM,Pomerantz WCK,Topczewski JJ

    更新日期：2019-08-02 00:00:00

  • Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.

    abstract：:We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncology target, culminating in target (in)validation. Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC50 = 0.043 nM). Cocrystalli...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.9b00420

    authors： Farand J,Kropf JE,Blomgren P,Xu J,Schmitt AC,Newby ZE,Wang T,Murakami E,Barauskas O,Sudhamsu J,Feng JY,Niedziela-Majka A,Schultz BE,Schwartz K,Viatchenko-Karpinski S,Kornyeyev D,Kashishian A,Fan P,Chen X,Lansdon EB

    更新日期：2019-11-19 00:00:00

  • The Dark Side of Fluorine.

    abstract：:Despite the perceived stability of the C-F bond, chemical instability and drug-metabolizing enzymes can lead to its cleavage. The resulting release of fluoride and formation of certain metabolites may cause safety issues and warrant the medicinal chemists' attention. ...

    journal_title：ACS medicinal chemistry letters

    pub_type： 社论

    doi：10.1021/acsmedchemlett.9b00235

    authors： Pan Y

    更新日期：2019-06-20 00:00:00

  • Discovery of CDK5 Inhibitors through Structure-Guided Approach.

    abstract：:Specific abrogation of cyclin-dependent kinase 5 (CDK5) activity has been validated as a viable approach for the development of anticancer agents. However, no selective CDK5 inhibitor has been reported to date. Herein, a structure-based in silico screening was employed to identify novel scaffolds from a library of com...

    journal_title：ACS medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1021/acsmedchemlett.9b00029

    authors： Khair NZ,Lenjisa JL,Tadesse S,Kumarasiri M,Basnet SKC,Mekonnen LB,Li M,Diab S,Sykes MJ,Albrecht H,Milne R,Wang S

    更新日期：2019-03-20 00:00:00