Full Text Journal Articles in
Journal J Med Chem

Advertisement

Find full text journal articles






Cytotoxic Effect of Silver Nanoparticles Synthesized by Green Methods in Cancer.

Mariana Morais, Ana Luísa Teixeira, Francisca Dias, Vera Machado, Rui Medeiros, João A V Prior,

Cancer is a major public health problem, but despite the several treatment approaches available, patients develop resistance in short time periods, making overcoming resistance or finding more efficient treatments an imperative challenge. Silver nanoparticles (AgNPs) have been described as an alternative option due to their physicochemical properties. The scope of ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Chemical Protein Synthesis in Medicinal Chemistry.

Vangelis Agouridas, Ouafâa El Mahdi, Oleg Melnyk,

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 are toxic for the expression ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Advertisement

Peptide Ligands Specifically Targeting HER2 Receptor and the Role Played by a Synthetic Model System of the Receptor Extracellular Domain: Hypothesized Future Perspectives.

Stefania De Luca, Valentina Verdoliva, Michele Saviano,

A short (Fab)trastuzumab-derived peptide specific for HER2 receptor was identified. Its affinity for the model system HER2-DIVMP was found in a nanomolar range. The structural determinants responsible for the interaction between this ligand (A9) and HER2-DIVMP were investigated by both computational and NMR analysis. Next, the possibility of using A9 ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Fragment-to-Lead Medicinal Chemistry Publications in 2019.

Wolfgang Jahnke, Daniel A Erlanson, Iwan J P de Esch, Christopher N Johnson, Paul N Mortenson, Yuji Ochi, Tatsuya Urushima,

Fragment-based drug discovery (FBDD) has grown and matured to a point where it is valuable to keep track of its extent and details of application. This Perspective summarizes successful fragment-to-lead stories published in 2019. It is the fifth in a series that started with literature published in 2015. The analysis ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Stabilization Strategies for Linear Minigastrin Analogues: Further Improvements via the Inclusion of Proline into the Peptide Sequence.

Maximilian Klingler, Anton A Hörmann, Christine Rangger, Laurence Desrues, Hélène Castel, Pierrick Gandolfo, Elisabeth von Guggenberg,

Minigastrin (MG) analogues, known for their high potential to target cholecystokinin-2 receptor (CCK2R) expressing tumors, have limited clinical applicability due to low enzymatic stability. By introducing site-specific substitutions within the C-terminal receptor-binding sequence, reduced metabolization and improved tumor targeting can be achieved. In this work, the influence of additional modification ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Discovery of BMS-986144, a Third-Generation, Pan-Genotype NS3/4A Protease Inhibitor for the Treatment of Hepatitis C Virus Infection.

Li-Qiang Sun, Eric Mull, Stanley D'Andrea, Barbara Zheng, Sheldon Hiebert, Eric Gillis, Michael Bowsher, Sarkunam Kandhasamy, Venkata Rao Baratam, Sunitha Puttaswamy, Nagalakshmi Pulicharla, Sureshbabu Vishwakrishnan, Subba Reddy, Ravi Trivedi, Sarmistha Sinha, Sankar Sivaprasad, Abhijith Rao, Salil Desai, Kaushik Ghosh, Rushith Anumula, Amit Kumar, Ramkumar Rajamani, Ying-Kai Wang, Hua Fang, Arvind Mathur, Richard Rampulla, Tatyana A Zvyaga, Kathy Mosure, Susan Jenkins, Paul Falk, Debarati M Tagore, Chaoqun Chen, Kishore Rendunchintala, James Loy, Nicholas A Meanwell, Fiona McPhee, Paul M Scola,

The discovery of a pan-genotypic hepatitis C virus (HCV) NS3/4A protease inhibitor based on a P1-P3 macrocyclic tripeptide motif is described. The all-carbon tether linking the P1-P3 subsites of 21 is functionalized with alkyl substituents, which are shown to effectively modulate both potency and absorption, distribution, metabolism, and excretion (ADME) ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Small-Molecule Inhibitors Directly Targeting KRAS as Anticancer Therapeutics.

Hao Chen, Jeff B Smaill, Tongzheng Liu, Ke Ding, Xiaoyun Lu,

KRAS, the most frequently mutated oncogene, plays a predominant role in driving initiation and progression of cancers. Decades of effort to target KRAS using small molecules has been unsuccessful, causing KRAS to be considered an "undruggable" cancer target. However, this view began to change recently, as drug discovery techniques have ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Photoactive Bifunctional Degraders: Precision Tools To Regulate Protein Stability.

Cyrille S Kounde, Edward W Tate,

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 attracted the interest of multiple research groups, ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Fragment-Based Discovery of Novel Non-Hydroxamate LpxC Inhibitors with Antibacterial Activity.

Yousuke Yamada, Hajime Takashima, David Lee Walmsley, Fumihito Ushiyama, Yohei Matsuda, Harumi Kanazawa, Toru Yamaguchi-Sasaki, Nozomi Tanaka-Yamamoto, Junya Yamagishi, Risa Kurimoto-Tsuruta, Yuya Ogata, Norikazu Ohtake, Hayley Angove, Lisa Baker, Richard Harris, Alba Macias, Alan Robertson, Allan Surgenor, Hayato Watanabe, Koichiro Nakano, Masashi Mima, Kunihiko Iwamoto, Atsushi Okada, Iichiro Takata, Kosuke Hitaka, Akihiro Tanaka, Kiyoko Fujita, Hiroyuki Sugiyama, Roderick E Hubbard,

UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) is a zinc metalloenzyme that catalyzes the first committed step in the biosynthesis of Lipid A, an essential component of the cell envelope of Gram-negative bacteria. The most advanced, disclosed LpxC inhibitors showing antibacterial activity coordinate zinc through a hydroxamate moiety with concerns about binding to other ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Pan-SMARCA/PB1 Bromodomain Inhibitors and Their Role in Regulating Adipogenesis.

Marek Wanior, Franziska Preuss, Xiaomin Ni, Andreas Krämer, Sebastian Mathea, Tamara Göbel, David Heidenreich, Svenja Simonyi, Astrid S Kahnt, Andreas C Joerger, Stefan Knapp,

Accessibility of the human genome is modulated by the ATP-driven SWI/SNF chromatin remodeling multiprotein complexes BAF (BRG1/BRM-associated factor) and PBAF (polybromo-associated BAF factor), which involves reading of acetylated histone tails by the bromodomain-containing proteins SMARCA2 (BRM), SMARCA4 (BRG1), and polybromo-1. Dysregulation of chromatin remodeling leads to aberrant cell proliferation and ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Therapeutic and Prophylactic Vaccines to Counteract Fentanyl Use Disorders and Toxicity.

Christine Robinson, Valeria Gradinati, Fatima Hamid, Carly Baehr, Bethany Crouse, Saadyah Averick, Marina Kovaliov, Danni Harris, Scott Runyon, Federico Baruffaldi, Mark LeSage, Sandra Comer, Marco Pravetoni,

The incidence of fatal overdoses has increased worldwide due to the widespread access to illicit fentanyl and its potent analogues. Vaccines offer a promising strategy to reduce the prevalence of opioid use disorders (OUDs) and to prevent toxicity from accidental and deliberate exposure to fentanyl and its derivatives. This study ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



From Pyrazolones to Azaindoles: Evolution of Active-Site SHP2 Inhibitors Based on Scaffold Hopping and Bioisosteric Replacement.

Yelena Mostinski, Guus J J E Heynen, Maria Pascual López-Alberca, Jerome Paul, Sandra Miksche, Silke Radetzki, David Schaller, Elena Shanina, Carola Seyffarth, Yuliya Kolomeets, Nandor Ziebart, Judith de Schryver, Sylvia Oestreich, Martin Neuenschwander, Yvette Roske, Udo Heinemann, Christoph Rademacher, Andrea Volkamer, Jens Peter von Kries, Walter Birchmeier, Marc Nazaré,

The tyrosine phosphatase SHP2 controls the activity of pivotal signaling pathways, including MAPK, JAK-STAT, and PI3K-Akt. Aberrant SHP2 activity leads to uncontrolled cell proliferation, tumorigenesis, and metastasis. SHP2 signaling was recently linked to drug resistance against cancer medications such as MEK and BRAF inhibitors. In this work, we present the ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Computational Fragment-Based Design Facilitates Discovery of Potent and Selective Monoamine Oxidase-B (MAO-B) Inhibitor.

Chuan-Fei Jin, Zhi-Zheng Wang, Kang-Zhi Chen, Teng-Fei Xu, Ge-Fei Hao,

Parkinson's disease (PD) is one of the most common age-related neurodegenerative diseases. Inhibition of monoamine oxidase-B (MAO-B), which is mainly found in the glial cells of the brain, may lead to an elevated level of dopamine (DA) in patients. MAO-B inhibitors have been used extensively for patients with PD. However, ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Design, Synthesis, and Structure-Activity Relationship Studies of (4-Alkoxyphenyl)glycinamides and Bioisosteric 1,3,4-Oxadiazoles as GPR88 Agonists.

Md Toufiqur Rahman, Ann M Decker, Tiffany L Langston, Kelly M Mathews, Lucas Laudermilk, Rangan Maitra, Weiya Ma, Emmanuel Darcq, Brigitte L Kieffer, Chunyang Jin,

Increasing evidence implicates the orphan G protein-coupled receptor 88 (GPR88) in a number of striatal-associated disorders. In this study, we report the design and synthesis of a series of novel (4-alkoxyphenyl)glycinamides (e.g., 31) and the corresponding 1,3,4-oxadiazole bioisosteres derived from the 2-AMPP scaffold (1) as GPR88 agonists. The 5-amino-1,3,4-oxadiazole derivatives ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Optimization of the In Vivo Potency of Pyrazolopyrimidine MALT1 Protease Inhibitors by Reducing Metabolism and Increasing Potency in Whole Blood.

Jean Quancard, Oliver Simic, Carole Pissot Soldermann, Reiner Aichholz, Markus Blatter, Martin Renatus, Paulus Erbel, Samu Melkko, Ralf Endres, Mickael Sorge, Laurence Kieffer, Trixie Wagner, Karen Beltz, Paul Mcsheehy, Markus Wartmann, Catherine H Régnier, Thomas Calzascia, Thomas Radimerski, Marc Bigaud, Andreas Weiss, Frédéric Bornancin, Achim Schlapbach,

The paracaspase MALT1 has gained increasing interest as a target for the treatment of subsets of lymphomas as well as autoimmune diseases, and there is a need for suitable compounds to explore the therapeutic potential of this target. Here, we report the optimization of the in vivo potency of pyrazolopyrimidines, ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



A Chemical Probe for Dark Kinase STK17B Derives Its Potency and High Selectivity through a Unique P-Loop Conformation.

Alfredo Picado, Apirat Chaikuad, Carrow I Wells, Safal Shrestha, William J Zuercher, Julie E Pickett, Frank E Kwarcinski, Parvathi Sinha, Chandi S de Silva, Reena Zutshi, Shubin Liu, Natarajan Kannan, Stefan Knapp, David H Drewry, Timothy M Willson,

STK17B is a member of the death-associated protein kinase family and has been genetically linked to the development of diverse diseases. However, the role of STK17B in normal and disease pathology is poorly defined. Here, we present the discovery of thieno[3,2-d] pyrimidine SGC-STK17B-1 (11s), a high-quality chemical probe for this ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Development of Indoleamine 2,3-Dioxygenase 1 Inhibitors for Cancer Therapy and Beyond: A Recent Perspective.

Xi Feng, Dongdong Liao, Dongyu Liu, An Ping, Zhiyu Li, Jinlei Bian,

Indoleamine 2,3-dioxygenase 1 (IDO1) has received increasing attention due to its immunosuppressive function in connection with various diseases, including cancer. A recent increase in the understanding of IDO1 has significantly contributed to the discovery of numerous novel inhibitors, but the latest clinical outcomes raised questions and have indicated a future ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Exploration of Structure-Activity Relationship of Aromatic Aldehydes Bearing Pyridinylmethoxy-Methyl Esters as Novel Antisickling Agents.

Piyusha P Pagare, Mohini S Ghatge, Qiukan Chen, Faik N Musayev, Jurgen Venitz, Osheiza Abdulmalik, Yan Zhang, Martin K Safo,

Aromatic aldehydes elicit their antisickling effects primarily by increasing the affinity of hemoglobin (Hb) for oxygen (O2). However, challenges related to weak potency and poor pharmacokinetic properties have hampered their development to treat sickle cell disease (SCD). Herein, we report our efforts to enhance the pharmacological profile of our previously ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Synthesis of Guaianolide Analogues with a Tunable α-Methylene-γ-lactam Electrophile and Correlating Bioactivity with Thiol Reactivity.

Paul A Jackson, Henry A M Schares, Katherine F M Jones, John C Widen, Daniel P Dempe, Francois Grillet, Matthew E Cuellar, Michael A Walters, Daniel A Harki, Kay M Brummond,

α-Methylene-γ-lactones are present in ∼3% of known natural products, and compounds comprising this motif display a range of biological activities. However, this reactive lactone limits informed structure-activity relationships for these bioactive molecules. Herein, we describe chemically tuning the electrophilicity of the α-methylene-γ-lactone by replacement with an α-methylene-γ-lactam. Guaianolide analogues having ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Design, Synthesis, and Characterization of an Orally Active Dual-Specific ULK1/2 Autophagy Inhibitor that Synergizes with the PARP Inhibitor Olaparib for the Treatment of Triple-Negative Breast Cancer.

Huiyu Ren, Nicole A Bakas, Mitchell Vamos, Apirat Chaikuad, Allison S Limpert, Carina D Wimer, Sonja N Brun, Lester J Lambert, Lutz Tautz, Maria Celeridad, Douglas J Sheffler, Stefan Knapp, Reuben J Shaw, Nicholas D P Cosford,

Inhibition of autophagy, the major cellular recycling pathway in mammalian cells, is a promising strategy for the treatment of triple-negative breast cancer (TNBC). We previously reported SBI-0206965, a small molecule inhibitor of unc-51-like autophagy activating kinase 1 (ULK1), which is a key regulator of autophagy initiation. Herein, we describe the ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Proline Hinged Amphipathic α-Helical Peptide Sensitizes Gram-Negative Bacteria to Various Gram-Positive Antibiotics.

Soonsil Hyun, Yoonhwa Choi, Doyeon Jo, Seolah Choo, Tae Woo Park, Su-Jin Park, Seoyeon Kim, Seonju Lee, Sohyun Park, Sun Mi Jin, Dae Hee Cheon, Wanki Yoo, Rekha Arya, Yong Pil Chong, Kyeong Kyu Kim, Yang Soo Kim, Yan Lee, Jaehoon Yu,

Gram-negative bacteria are becoming resistant to almost all currently available antibiotics. Systemically designed antimicrobial peptides (AMPs) are attractive agents to enhance the activities of antibiotics. We constructed a small Pro-scanning library using amphipathic model peptides. Measurements of minimum inhibitory concentration (MIC) against Escherichia coli and hemolytic activities showed that one ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Selectively Targeting Tropomyosin Receptor Kinase A (TRKA) via PROTACs.

Weiguo Xiang, Shaomeng Wang,

Tropomyosin receptor kinases (TRKs) are promising cancer therapeutic targets. Chen ( J. Med. Chem. 2020, DOI: 10.1021/acs.jmedchem.0c01342) report the discovery of CG416 and CG428 as two potent small-molecule proteolysis-targeting chimera (PROTAC) degraders selective for TRKA over TRKB and TRKC. CG416 and CG428 are valuable research tool compounds for in vitro ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Recent Advances in β2-Agonists for Treatment of Chronic Respiratory Diseases and Heart Failure.

Gang Xing, Anthony Yiu-Ho Woo, Li Pan, Bin Lin, Mao-Sheng Cheng,

β2-Adrenoceptor (β2-AR) agonists are widely used as bronchodilators. The emerge of ultralong acting β2-agonists is an important breakthrough in pulmonary medicine. In this review, we will provide mechanistic insights into the application of β2-agonists in asthma, chronic obstructive pulmonary disease (COPD), and heart failure (HF). Recent studies in β-AR signal ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Design and Optimization of an Acyclic Amine Series of TRPV4 Antagonists by Electronic Modulation of Hydrogen Bond Interactions.

Jaclyn R Patterson, Lamont R Terrell, Carla A Donatelli, Dennis A Holt, Larry J Jolivette, Ralph A Rivero, Theresa J Roethke, Arthur Shu, Patrick Stoy, Guosen Ye, Mark Youngman, Brian G Lawhorn,

Investigation of TRPV4 as a potential target for the treatment of pulmonary edema associated with heart failure generated a novel series of acyclic amine inhibitors displaying exceptional potency and PK properties. The series arose through a scaffold hopping approach, which relied on use of an internal H-bond to replace a ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



SAR Investigation and Discovery of Water-Soluble 1-Methyl-1,4-dihydroindeno[1,2-c]pyrazoles as Potent Tubulin Polymerization Inhibitors.

Ying-Jie Cui, Chao Liu, Chen-Chen Ma, Ya-Ting Ji, Yi-Li Yao, Long-Qian Tang, Cheng-Mei Zhang, Jing-De Wu, Zhao-Peng Liu,

Taking the previously discovered 1-methyl-1,4-dihydroindeno[1,2c]pyrazol derivative LL01 as a lead, systematic structural modifications were made at the phenolic 6- and 7-positions and the aniline at the 3-position of the indenopyrazole core to investigate the SARs and to improve water solubility. Among the designed indenopyrazoles ID01-ID33, a series of potent MTAs ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2020, :]

Cited: 0 times

View full text PDF listing >>



Advertisement

Disclaimer
1.0659 s