听力与言语-语言病理学

行为科学

医学伦理学

你正在浏览JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献
  • Targeting Necrosis: Elastase-like Protease Inhibitors Curtail Necrotic Cell Death Both In Vitro and in Three In Vivo Disease Models.

    abstract::Necrosis is the main mode of cell death, which leads to multiple clinical conditions affecting hundreds of millions of people worldwide. Its molecular mechanisms are poorly understood, hampering therapeutics development. Here, we identify key proteolytic activities essential for necrosis using various biochemical appr...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01683

    authors: Khalfin B,Lichtenstein A,Albeck A,Nathan I

    更新日期:2021-01-31 00:00:00

  • GPR52 Antagonist Reduces Huntingtin Levels and Ameliorates Huntington's Disease-Related Phenotypes.

    abstract::GPR52 is an orphan G protein-coupled receptor (GPCR) that has been recently implicated as a potential drug target of Huntington's disease (HD), an incurable monogenic neurodegenerative disorder. In this research, we found that striatal knockdown of GPR52 reduces mHTT levels in adult HdhQ140 mice, validating GPR52 as a...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01133

    authors: Wang C,Zhang YF,Guo S,Zhao Q,Zeng Y,Xie Z,Xie X,Lu B,Hu Y

    更新日期:2021-01-28 00:00:00

  • Mining Natural Products for Macrocycles to Drug Difficult Targets.

    abstract::Lead generation for difficult-to-drug targets that have large, featureless, and highly lipophilic or highly polar and/or flexible binding sites is highly challenging. Here, we describe how cores of macrocyclic natural products can serve as a high-quality in silico screening library that provides leads for difficult-to...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01569

    authors: Begnini F,Poongavanam V,Over B,Castaldo M,Geschwindner S,Johansson P,Tyagi M,Tyrchan C,Wissler L,Sjö P,Schiesser S,Kihlberg J

    更新日期:2021-01-28 00:00:00

  • Structure-Activity Relationship and Biological Investigation of SR18292 (16), a Suppressor of Glucagon-Induced Glucose Production.

    abstract::Despite a myriad of available pharmacotherapies for the treatment of type 2 diabetes (T2D), challenges still exist in achieving glycemic control. Several novel glucose-lowering strategies are currently under clinical investigation, highlighting the need for more robust treatments. Previously, we have shown that suppre...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01450

    authors: Lin H,Sharabi K,Lin L,Ruiz C,Zhu D,Cameron MD,Novick SJ,Griffin PR,Puigserver P,Kamenecka TM

    更新日期:2021-01-28 00:00:00

  • 1-Methyl-1H-pyrazole-5-carboxamide Derivatives Exhibit Unexpected Acute Mammalian Toxicity.

    abstract::A series of 1-methyl-1H-pyrazole-5-carboxamides were synthesized as potent inhibitors of the parasitic nematode of sheep, Haemonchus contortus. These compounds did not show overt cytotoxicity to a range of mammalian cell lines under standard in vitro culture conditions, had high selectivity indices, and were progresse...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01793

    authors: Preston S,Garcia-Bustos J,Hall LG,Martin SD,Le TG,Kundu A,Ghoshal A,Nguyen NH,Jiao Y,Ruan B,Xue L,Huang F,Chang BCH,McGee SL,Wells TNC,Palmer MJ,Jabbar A,Gasser RB,Baell JB

    更新日期:2021-01-14 00:00:00

  • 3,4-Dihydropyrimidin-2(1H)-ones as Antagonists of the Human A2B Adenosine Receptor: Optimization, Structure-Activity Relationship Studies, and Enantiospecific Recognition.

    abstract::We present and thoroughly characterize a large collection of 3,4-dihydropyrimidin-2(1H)-ones as A2BAR antagonists, an emerging strategy in cancer (immuno) therapy. Most compounds selectively bind A2BAR, with a number of potent and selective antagonists further confirmed by functional cyclic adenosine monophosphate exp...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01431

    authors: Majellaro M,Jespers W,Crespo A,Núñez MJ,Novio S,Azuaje J,Prieto-Díaz R,Gioé C,Alispahic B,Brea J,Loza MI,Freire-Garabal M,Garcia-Santiago C,Rodríguez-García C,García-Mera X,Caamaño O,Fernandez-Masaguer C,Sardina JF,St

    更新日期:2021-01-14 00:00:00

  • Development of Orally Efficacious Allosteric Inhibitors of TNFα via Fragment-Based Drug Design.

    abstract::Tumor necrosis factor α (TNFα) is a soluble cytokine that is directly involved in systemic inflammation through the regulation of the intracellular NF-κB and MAPK signaling pathways. The development of biologic drugs that inhibit TNFα has led to improved clinical outcomes for patients with rheumatoid arthritis and oth...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01280

    authors: Dietrich JD,Longenecker KL,Wilson NS,Goess C,Panchal SC,Swann SL,Petros AM,Hobson AD,Ihle D,Song D,Richardson P,Comess KM,Cox PB,Dombrowski A,Sarris K,Donnelly-Roberts DL,Duignan DB,Gomtsyan A,Jung P,Krueger AC,Ma

    更新日期:2021-01-14 00:00:00

  • Spirocyclic Scaffolds in Medicinal Chemistry.

    abstract::Spirocyclic scaffolds are incorporated in various approved drugs and drug candidates. The increasing interest in less planar bioactive compounds has given rise to the development of synthetic methodologies for the preparation of spirocyclic scaffolds. In this Perspective, we summarize the diverse synthetic routes to o...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01473

    authors: Hiesinger K,Dar'in D,Proschak E,Krasavin M

    更新日期:2021-01-14 00:00:00

  • Discovery of Benzopyridone-Based Transient Receptor Potential Vanilloid 1 Agonists and Antagonists and the Structural Elucidation of Their Activity Shift.

    abstract::Among a series of benzopyridone-based scaffolds investigated as human transient receptor potential vanilloid 1 (TRPV1) ligands, two isomeric benzopyridone scaffolds demonstrated a consistent and distinctive functional profile in which 2-oxo-1,2-dihydroquinolin-5-yl analogues (e.g., 2) displayed high affinity and poten...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c00982

    authors: Thorat SA,Lee Y,Jung A,Ann J,Ahn S,Baek J,Zuo D,Do N,Jeong JJ,Blumberg PM,Esch TE,Turcios NA,Pearce LV,Ha HJ,Yoo YD,Hong S,Choi S,Lee J

    更新日期:2021-01-14 00:00:00

  • Photoactive Bifunctional Degraders: Precision Tools To Regulate Protein Stability.

    abstract::Targeted protein degradation with bifunctional degraders is positioned as a remarkable game-changing strategy to control cellular protein levels and promises a new therapeutic modality in drug discovery. Light activation of a degrader to achieve exquisite spatiotemporal control over protein stability in cells has attr...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01542

    authors: Kounde CS,Tate EW

    更新日期:2020-12-24 00:00:00

  • Chemical Protein Synthesis in Medicinal Chemistry.

    abstract::Although the majority of proteins used for biomedical research are produced using living systems such as bacteria, biological means for producing proteins can be advantageously complemented by protein semisynthesis or total chemical synthesis. The latter approach is particularly useful when the proteins to be produced...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01082

    authors: Agouridas V,El Mahdi O,Melnyk O

    更新日期:2020-12-24 00:00:00

  • Synthesis and Biological Characterization of Cyclic Disulfide-Containing Peptide Analogs of the Multifunctional Opioid/Neuropeptide FF Receptor Agonists That Produce Long-Lasting and Nontolerant Antinociception.

    abstract::In a previously described chimeric peptide, we reported that the multifunctional opioid/neuropeptide FF (NPFF) receptor agonist 0 (BN-9) produced antinociception for 1.5 h after supraspinal administration. Herein, four cyclic disulfide analogs containing l- and/or d-type cysteine at positions 2 and 5 were synthesized....

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01367

    authors: Zhang M,Xu B,Li N,Liu H,Shi X,Zhang Q,Shi Y,Xu K,Xiao J,Chen D,Zhu H,Sun Y,Zhang T,Zhang R,Fang Q

    更新日期:2020-12-24 00:00:00

  • Discovery of a Potent Adenine-Benzyltriazolo-Pleuromutilin Conjugate with Pronounced Antibacterial Activity against MRSA.

    abstract::Conjugation of pleuromutilin is an attractive strategy for the development of novel antibiotics and the fight against multiresistant bacteria as the class is associated with low rates of resistance and cross-resistance development. Herein, the preparation of 35 novel (+)-pleuromutilin conjugates is reported. Their des...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01328

    authors: Heidtmann CV,Voukia F,Hansen LN,Sørensen SH,Urlund B,Nielsen S,Pedersen M,Kelawi N,Andersen BN,Pedersen M,Reinholdt P,Kongsted J,Nielsen CU,Klitgaard JK,Nielsen P

    更新日期:2020-12-24 00:00:00

  • Progress in the Development of Small Molecular Inhibitors of Focal Adhesion Kinase (FAK).

    abstract::Focal adhesion kinase (FAK) is a nonreceptor intracellular tyrosine kinase that plays an essential role in cancer cell adhesion, survival, proliferation, and migration through both its enzymatic activities and scaffolding functions. Overexpression of FAK has been found in many human cancer cells from different origins...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.1021/acs.jmedchem.0c01248

    authors: Lu Y,Sun H

    更新日期:2020-12-10 00:00:00

  • Discovery of First-In-Class Potent and Selective Tropomyosin Receptor Kinase Degraders.

    abstract::We report compounds 5 (CG416) and 6 (CG428) as two first-in-class tropomyosin receptor kinase (TRK) degraders that target the intracellular kinase domain of TRK. Degraders 5 and 6 reduced levels of the tropomyosin 3 (TPM3)-TRKA fusion protein in KM12 colorectal carcinoma cells and inhibited downstream PLCγ1 signaling ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01342

    authors: Chen L,Chen Y,Zhang C,Jiao B,Liang S,Tan Q,Chai H,Yu W,Qian Y,Yang H,Yao W,Yu J,Luo Y,Plewe M,Wang J,Han XR,Liu J

    更新日期:2020-12-10 00:00:00

  • Hydroxamate-Based Selective Macrophage Elastase (MMP-12) Inhibitors and Radiotracers for Molecular Imaging.

    abstract::Macrophage elastase [matrix metalloproteinase (MMP)-12] is the most upregulated MMP in abdominal aortic aneurysm (AAA) and, hence, MMP-12-targeted imaging may predict AAA progression and rupture risk. Here, we report the design, synthesis, and evaluation of three novel hydroxamate-based selective MMP-12 inhibitors (CG...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01514

    authors: Gona K,Toczek J,Ye Y,Sanzida N,Golbazi A,Boodagh P,Salarian M,Jung JJ,Rajendran S,Kukreja G,Wu TL,Devel L,Sadeghi MM

    更新日期:2020-12-10 00:00:00

  • N-(Pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine Derivatives as Selective Janus Kinase 2 Inhibitors for the Treatment of Myeloproliferative Neoplasms.

    abstract::In this study, we described a series of N-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine derivatives as selective JAK2 (Janus kinase 2) inhibitors. Systematic exploration of the structure-activity relationship though cyclization modification based on previously reported compound 18e led to the discovery of the...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01488

    authors: Yang T,Hu M,Chen Y,Xiang M,Tang M,Qi W,Shi M,He J,Yuan X,Zhang C,Liu K,Li J,Yang Z,Chen L

    更新日期:2020-12-10 00:00:00

  • Structure-Based Drug Design of Bisubstrate Inhibitors of Phenylethanolamine N-Methyltransferase Possessing Low Nanomolar Affinity at Both Substrate Binding Domains1.

    abstract::The enzyme phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) catalyzes the final step in the biosynthesis of epinephrine and is a potential drug target, primarily for the control of hypertension. Unfortunately, many potent PNMT inhibitors also possess significant affinity for the a2-adrenoceptor, which compli...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01475

    authors: Lu J,Bart AG,Wu Q,Criscione KR,McLeish MJ,Scott EE,Grunewald GL

    更新日期:2020-11-25 00:00:00

  • Identification of a New Heterocyclic Scaffold for Inhibitors of the Polo-Box Domain of Polo-like Kinase 1.

    abstract::As a mitotic-specific target widely deregulated in various human cancers, polo-like kinase 1 (Plk1) has been extensively explored for anticancer activity and drug discovery. Although multiple catalytic domain inhibitors were tested in preclinical and clinical studies, their efficacies are limited by dose-limiting cyto...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01669

    authors: Alverez CN,Park JE,Toti KS,Xia Y,Krausz KW,Rai G,Bang JK,Gonzalez FJ,Jacobson KA,Lee KS

    更新日期:2020-11-25 00:00:00

  • Design, Synthesis, and Biological Evaluation of Linear Aliphatic Amine-Linked Triaryl Derivatives as Potent Small-Molecule Inhibitors of the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Interaction with Promising Antitumor Effects In Vivo.

    abstract::A series of novel linear aliphatic amine-linked triaryl derivatives as inhibitors of PD-1/PD-L1 were designed, synthesized, and evaluated in vitro and in vivo. In this chemical series, compound 58 showed the most potent inhibitory activity and binding affinity with hPD-L1, with an IC50 value of 12 nM and a KD value of...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01329

    authors: Guo J,Luo L,Wang Z,Hu N,Wang W,Xie F,Liang E,Yan X,Xiao J,Li S

    更新日期:2020-11-25 00:00:00

  • Targeting the Allosteric Pathway That Interconnects the Core-Functional Scaffold and the Distal Phosphorylation Sites for Specific Dephosphorylation of Bcl-2.

    abstract::Protein phosphorylation is the most significant post-translational modification for regulating cellular activities, but site-specific modulation of phosphorylation is still challenging. Using three-dimensional NMR spectra, molecular dynamics simulations, and alanine mutations, we identified that the interaction networ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01290

    authors: Wang Z,Song T,Guo Z,Cao K,Chen C,Feng Y,Wang H,Yin F,Zhou S,Dai J,Zhang Z

    更新日期:2020-11-25 00:00:00

  • Amide Bond Bioisosteres: Strategies, Synthesis, and Successes.

    abstract::The amide functional group plays a key role in the composition of biomolecules, including many clinically approved drugs. Bioisosterism is widely employed in the rational modification of lead compounds, being used to increase potency, enhance selectivity, improve pharmacokinetic properties, eliminate toxicity, and acq...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.1021/acs.jmedchem.0c00530

    authors: Kumari S,Carmona AV,Tiwari AK,Trippier PC

    更新日期:2020-11-12 00:00:00

  • Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19.

    abstract::The novel coronavirus disease COVID-19 that emerged in 2019 is caused by the virus SARS CoV-2 and named for its close genetic similarity to SARS CoV-1 that caused severe acute respiratory syndrome (SARS) in 2002. Both SARS coronavirus genomes encode two overlapping large polyproteins, which are cleaved at specific sit...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01063

    authors: Hoffman RL,Kania RS,Brothers MA,Davies JF,Ferre RA,Gajiwala KS,He M,Hogan RJ,Kozminski K,Li LY,Lockner JW,Lou J,Marra MT,Mitchell LJ Jr,Murray BW,Nieman JA,Noell S,Planken SP,Rowe T,Ryan K,Smith GJ 3rd,Solowiej

    更新日期:2020-11-12 00:00:00

  • Drug Induced Liver Injury (DILI). Mechanisms and Medicinal Chemistry Avoidance/Mitigation Strategies.

    abstract::Adverse drug reactions (ADRs) are a common cause of attrition in drug discovery and development and drug-induced liver injury (DILI) is a leading cause of preclinical and clinical drug terminations. This perspective outlines many of the known DILI mechanisms and assessment methods used to evaluate and mitigate DILI ri...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.1021/acs.jmedchem.0c00524

    authors: Norman BH

    更新日期:2020-10-22 00:00:00

  • 7-Hydroxycoumarins Are Affinity-Based Fluorescent Probes for Competitive Binding Studies of Macrophage Migration Inhibitory Factor.

    abstract::Macrophage migration inhibitory factor (MIF) is a cytokine with key roles in inflammation and cancer, which qualifies it as a potential drug target. Apart from its cytokine activity, MIF also harbors enzyme activity for keto-enol tautomerization. MIF enzymatic activity has been used for identification of MIF binding m...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01160

    authors: Xiao Z,Chen D,Song S,van der Vlag R,van der Wouden PE,van Merkerk R,Cool RH,Hirsch AKH,Melgert BN,Quax WJ,Poelarends GJ,Dekker FJ

    更新日期:2020-10-22 00:00:00

  • Potent and Selective Human Prostaglandin F (FP) Receptor Antagonist (BAY-6672) for the Treatment of Idiopathic Pulmonary Fibrosis (IPF).

    abstract::Idiopathic pulmonary fibrosis (IPF) is a rare and devastating chronic lung disease of unknown etiology. Despite the approved treatment options nintedanib and pirfenidone, the medical need for a safe and well-tolerated antifibrotic treatment of IPF remains high. The human prostaglandin F receptor (hFP-R) is widely expr...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c00834

    authors: Beck H,Thaler T,Meibom D,Meininghaus M,Jörißen H,Dietz L,Terjung C,Bairlein M,von Bühler CJ,Anlauf S,Fürstner C,Stellfeld T,Schneider D,Gericke KM,Buyck T,Lovis K,Münster U,Anlahr J,Kersten E,Levilain G,Marossek V

    更新日期:2020-10-22 00:00:00

  • Discovery of Potent and Selective PI3Kγ Inhibitors.

    abstract::The selective inhibition of the lipid signaling enzyme PI3Kγ constitutes an opportunity to mediate immunosuppression and inflammation within the tumor microenvironment but is difficult to achieve due to the high sequence homology across the class I PI3K isoforms. Here, we describe the design of a novel series of poten...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01203

    authors: Drew SL,Thomas-Tran R,Beatty JW,Fournier J,Lawson KV,Miles DH,Mata G,Sharif EU,Yan X,Mailyan AK,Ginn E,Chen J,Wong K,Soni D,Dhanota P,Chen PY,Shaqfeh SG,Meleza C,Pham AT,Chen A,Zhao X,Banuelos J,Jin L,Schind

    更新日期:2020-10-08 00:00:00

  • Design and SAR of Withangulatin A Analogues that Act as Covalent TrxR Inhibitors through the Michael Addition Reaction Showing Potential in Cancer Treatment.

    abstract::The thioredoxin system plays an important role in cancer cells. Inhibiting thioredoxin reductase (TrxR) has emerged as an effective strategy to selectively target cancer cells. Withangulatin A (WA), a natural product extracted from the whole herb of Physalis angulata L. (Solanaceae), exhibits potent anticancer activit...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01128

    authors: Wang C,Li S,Zhao J,Yang H,Yin F,Ding M,Luo J,Wang X,Kong L

    更新日期:2020-10-08 00:00:00

  • Design, Synthesis, and Structure-Activity Relationships of Indoline-Based Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-Derived 2)-Like 2 (Keap1-Nrf2) Protein-Protein Interaction Inhibitors.

    abstract::The Keap1 (Kelch-like ECH-associated protein 1)-Nrf2 (nuclear factor erythroid 2-related factor 2)-ARE (antioxidant response element) pathway is the major defending mechanism against oxidative stresses, and directly disrupting the Keap1-Nrf2 protein-protein interaction (PPI) has been an attractive strategy to target o...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c01116

    authors: Zhou HS,Hu LB,Zhang H,Shan WX,Wang Y,Li X,Liu T,Zhao J,You QD,Jiang ZY

    更新日期:2020-10-08 00:00:00

  • Multicomponent Synthesis, Binding Mode, and Structure-Activity Relationship of Selective Histone Deacetylase 6 (HDAC6) Inhibitors with Bifurcated Capping Groups.

    abstract::Histone deacetylase 6 (HDAC6) is an emerging target for the treatment of cancer, neurodegenerative diseases, inflammation, and other diseases. Here, we present the multicomponent synthesis and structure-activity relationship of a series of tetrazole-based HDAC6 inhibitors. We discovered the hit compound NR-160 by inve...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.9b01888

    authors: Reßing N,Sönnichsen M,Osko JD,Schöler A,Schliehe-Diecks J,Skerhut A,Borkhardt A,Hauer J,Kassack MU,Christianson DW,Bhatia S,Hansen FK

    更新日期:2020-09-24 00:00:00

  • Discovery of a Monoiodo Aza-BODIPY Near-Infrared Photosensitizer: in vitro and in vivo Evaluation for Photodynamic Therapy.

    abstract::Photodynamic therapy (PDT) as a rising platform of the cancer treatment method is receiving increased attention. Through systematic evaluation of halogen substitution on aza-4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (BODIPY), we have found that monoiodo-derived aza-BODIPYs provided greater efficacy than other haloge...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c00882

    authors: Yu Z,Zhou J,Ji X,Lin G,Xu S,Dong X,Zhao W

    更新日期:2020-09-10 00:00:00

  • Structural Analysis of VDR Complex with ZK168281 Antagonist.

    abstract::Vitamin D receptor (VDR) antagonists prevent the VDR activation function helix 12 from folding into its active conformation, thus affecting coactivator recruitment and antagonizing the transcriptional regulation induced by 1α,25-dihydroxyvitamin D3. Here, we report the crystal structure of the zebrafish VDR ligand-bin...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c00656

    authors: Belorusova AY,Chalhoub S,Rovito D,Rochel N

    更新日期:2020-09-10 00:00:00

  • Pharmacological Characterization of Low-to-Moderate Affinity Opioid Receptor Agonists and Brain Imaging with 18F-Labeled Derivatives in Rats.

    abstract::The 3,4-dichloro-N-(1-(dimethylamino)cyclohexyl)methyl benzamide scaffold was studied as a template for 18F-positron emission tomography (18F-PET) radiotracer development emphasizing sensitivity to changes in opioid receptor (OR) occupancy over high affinity. Agonist potency, binding affinity, and relevant pharmacolog...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c00683

    authors: Ott J,Spilhaug MM,Maschauer S,Rafique W,Jakobsson JE,Hartvig K,Hübner H,Gmeiner P,Prante O,Riss PJ

    更新日期:2020-09-10 00:00:00

  • Discovery of IACS-9439, a Potent, Exquisitely Selective, and Orally Bioavailable Inhibitor of CSF1R.

    abstract::Tumor-associated macrophages (TAMs) have a significant presence in the tumor stroma across multiple human malignancies and are believed to be beneficial to tumor growth. Targeting CSF1R has been proposed as a potential therapy to reduce TAMs, especially the protumor, immune-suppressive M2 TAMs. Additionally, the high ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c00936

    authors: Czako B,Marszalek JR,Burke JP,Mandal P,Leonard PG,Cross JB,Mseeh F,Jiang Y,Chang EQ,Suzuki E,Kovacs JJ,Feng N,Gera S,Harris AL,Liu Z,Mullinax RA,Pang J,Parker CA,Spencer ND,Yu SS,Wu Q,Tremblay MR,Mikule K,Wi

    更新日期:2020-09-10 00:00:00

  • Development of Potent PfCLK3 Inhibitors Based on TCMDC-135051 as a New Class of Antimalarials.

    abstract::The protein kinase PfCLK3 plays a critical role in the regulation of malarial parasite RNA splicing and is essential for the survival of blood stage Plasmodium falciparum. We recently validated PfCLK3 as a drug target in malaria that offers prophylactic, transmission blocking, and curative potential. Herein, we descri...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c00451

    authors: Mahindra A,Janha O,Mapesa K,Sanchez-Azqueta A,Alam MM,Amambua-Ngwa A,Nwakanma DC,Tobin AB,Jamieson AG

    更新日期:2020-09-10 00:00:00

  • Tailoring the Physicochemical Properties of Antimicrobial Peptides onto a Thiazole-Based γ-Peptide Foldamer.

    abstract::Antimicrobial peptides (AMPs) are amphipathic molecules displaying broad-spectrum bactericidal activity, providing opportunities to develop a new generation of antibiotics. However, their use is limited either by poor metabolic stability or by high hemolytic activity. We herein addressed the potential of thiazole-base...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c00077

    authors: Bonnel C,Legrand B,Simon M,Clavié M,Masnou A,Jumas-Bilak E,Kang YK,Licznar-Fajardo P,Maillard LT,Masurier N

    更新日期:2020-09-10 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

  • Drug Research Meets Network Science: Where Are We?

    abstract::Network theory provides one of the most potent analysis tools for the study of complex systems. In this paper, we illustrate the network-based perspective in drug research and how it is coherent with the new paradigm of drug discovery. We first present data sources from which networks are built, then show some example...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.9b01989

    authors: Recanatini M,Cabrelle C

    更新日期:2020-08-27 00:00:00

  • Nitrogen-Walk Approach to Explore Bioisosteric Replacements in a Series of Potent A2B Adenosine Receptor Antagonists.

    abstract::A systematic exploration of bioisosteric replacements for furan and thiophene cores in a series of potent A2BAR antagonists has been carried out using the nitrogen-walk approach. A collection of 42 novel alkyl 4-substituted-2-methyl-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylates, which contain 18 differe...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c00564

    authors: Mallo-Abreu A,Prieto-Díaz R,Jespers W,Azuaje J,Majellaro M,Velando C,García-Mera X,Caamaño O,Brea J,Loza MI,Gutiérrez-de-Terán H,Sotelo E

    更新日期:2020-07-23 00:00:00

  • Characterization of Inhibition Reveals Distinctive Properties for Human and Saccharomyces cerevisiae CRM1.

    abstract::The receptor CRM1 is responsible for the nuclear export of many tumor-suppressor proteins and viral ribonucleoproteins. This renders CRM1 an interesting target for therapeutic intervention in diverse cancer types and viral diseases. Structural studies of Saccharomyces cerevisiae CRM1 ( Sc ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c00143

    authors: Shaikhqasem A,Dickmanns A,Neumann P,Ficner R

    更新日期:2020-07-23 00:00:00

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