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Identification of Novel Tricyclic Benzo[1,3]oxazinyloxazolidinones as Potent Antibacterial Agents with Excellent Pharmacokinetic Profiles against Drug-Resistant Pathogens

期刊: JOURNAL OF MEDICINAL CHEMISTRY, 2021; 64 (6)

A series of conformationally constrained novel benzo[1,3]oxazinyloxazolidinones were designed, synthesized, and evaluated on their activities against ......

Developing a Novel Anticancer Gold(III) Agent to Integrate Chemotherapy and Immunotherapy

期刊: JOURNAL OF MEDICINAL CHEMISTRY, 2021; 64 (10)

To effectively treat gastric cancer, we innovatively attempted to develop a metal agent to integrate immunotherapy and chemotherapy by dual targeting ......

Design, Synthesis, and Evaluation of o-(Biphenyl-3-ylmethoxy)nitrophenyl Derivatives as PD-1/PD-L1 Inhibitors with Potent Anticancer Efficacy In Vivo

期刊: JOURNAL OF MEDICINAL CHEMISTRY, 2021; 64 (11)

Two series of novel o-(biphenyl-3-ylmethoxy)nitrophenyl compounds (A1-31 and B1-17) were designed as programmed cell death protein 1 (PD-1)/PD-ligand ......

Inhibiting Eukaryotic Elongation Factor 2 Kinase: An Update on Pharmacological Small-Molecule Compounds in Cancer

期刊: JOURNAL OF MEDICINAL CHEMISTRY, 2021; 64 (13)

Eukaryotic elongation factor 2 kinase (eEF2K), a member of the atypical protein kinase family of alpha-kinases, is well-known as a negative regulator ......

Structure-Based Optimization of 3-Phenyl-N-(2-(3-phenylureido)ethyl)thiophene-2-sulfonamide Derivatives as Selective Mcl-1 Inhibitors

期刊: JOURNAL OF MEDICINAL CHEMISTRY, 2021; 64 (14)

Selective Mcl-1 inhibitors may overcome the drug resistance caused by current anti-apoptotic Bcl-2 protein inhibitors in tumors with Mcl-1 overexpress......

Improving Druggability of Novel Diarylpyrimidine NNRTIs by a Fragment-Based Replacement Strategy: From Biphenyl-DAPYs to Heteroaromatic-Biphenyl-DAPYs

期刊: JOURNAL OF MEDICINAL CHEMISTRY, 2021; 64 (14)

A series of novel heteroaromatic-difluoro-biphenyl-diarylpyrimidines were designed as non-nucleoside anti-HIV inhibitors targeting reverse transcripta......

Novel Broad-Spectrum Antimicrobial Peptide Derived from Anoplin and Its Activity on Bacterial Pneumonia in Mice

期刊: JOURNAL OF MEDICINAL CHEMISTRY, 2021; 64 (15)

The emergence of multidrug-resistant bacteria has major issues for treating bacterial pneumonia. Currently, anoplin (GLLKRIKTLL-NH2) is a natural anti......

Discovery, Synthesis, and Evaluation of Highly Selective Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Inhibitor for the Potential Treatment of Metastatic Triple-Negative Breast Cancer

期刊: JOURNAL OF MEDICINAL CHEMISTRY, 2021; 64 (16)

We herein report the identification, structural optimization, and structure-activity relationship of thieno[2,3-d]pyrimidine derivatives as a novel ki......

Engineered Conotoxin Differentially Blocks and Discriminates Rat and Human alpha 7 Nicotinic Acetylcholine Receptors

期刊: JOURNAL OF MEDICINAL CHEMISTRY, 2021; 64 (9)

The alpha 7 nicotinic acetylcholine receptor (nAChR) is present in the central nervous system and plays an important role in cognitive function and me......

Discovery of a Vitamin D Receptor-Silent Vitamin D Derivative That Impairs Sterol Regulatory Element-Binding Protein In Vivo

期刊: JOURNAL OF MEDICINAL CHEMISTRY, 2021; 64 (9)

Vitamin D-3 metabolites inhibit the expression of lipogenic genes by impairing sterol regulatory element-binding protein (SREBP), a master transcripti......

Highly Potent and Selective Butyrylcholinesterase Inhibitors for Cognitive Improvement and Neuroprotection

期刊: JOURNAL OF MEDICINAL CHEMISTRY, 2021; 64 (10)

Butyrylcholinesterase (BChE) has been considered as a potential therapeutic target for Alzheimer's disease (AD) because of its compensation capacity t......

Discovery of the Next-Generation Pan-TRK Kinase Inhibitors for the Treatment of Cancer

期刊: JOURNAL OF MEDICINAL CHEMISTRY, 2021; 64 (14)

The neurotrophic receptor tyrosine kinase (NTRK) genes including NTRK1, NTRK2, and NTRK3 encode the tropomyosin receptor kinase (Trk) proteins TrkA, T......

Molecular Glues for Targeted Protein Degradation: From Serendipity to Rational Discovery

期刊: JOURNAL OF MEDICINAL CHEMISTRY, 2021; 64 (15)

Targeted protein degradation is a promising area in the discovery and development of innovative therapeutics. Molecular glues mediate proximity-induce......

Proteases and Their Modulators in Cancer Therapy: Challenges and Opportunities

期刊: JOURNAL OF MEDICINAL CHEMISTRY, 2021; 64 (6)

Proteostasis is the process of regulating intracellular proteins to maintain the balance of the cell proteome, which is crucial for cancer cell surviv......

Discovery of Novel and Potent N-Methyl-D-aspartate Receptor Positive Allosteric Modulators with Antidepressant-like Activity in Rodent Models

期刊: JOURNAL OF MEDICINAL CHEMISTRY, 2021; 64 (9)

N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated Na+ and Ca2+-permeable ion channels involved in excitatory synaptic transmission and synap......

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