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European Journal of Medicinal Chemistry Jun 2024Drugs have structural homology across similar biological targets. Small molecule drugs have the efficacy to target specific molecular targets within the cancer cells... (Review)
Review
Drugs have structural homology across similar biological targets. Small molecule drugs have the efficacy to target specific molecular targets within the cancer cells with enhanced cell membrane permeability, oral administration, selectivity, and specific affinity. The objective of this review is to highlight the clinical importance and synthetic routes of new small molecule oncology drugs approved by the FDA during the period 2021-2022. These marketed drugs are listed based on the month and year of approval in chronological order. We believed that an in-depth insight into the synthetic approaches for the construction of these chemical entities would enhance the ability to develop new drugs more efficiently.
Topics: Humans; Antineoplastic Agents; Drug Approval; Small Molecule Libraries; Neoplasms; Molecular Structure; United States; United States Food and Drug Administration
PubMed: 38759455
DOI: 10.1016/j.ejmech.2024.116441 -
FEBS Letters Aug 2023RNA-binding proteins (RBPs) play vital roles in organisms through binding with RNAs to regulate their functions. Small molecules affecting the function of RBPs have been... (Review)
Review
RNA-binding proteins (RBPs) play vital roles in organisms through binding with RNAs to regulate their functions. Small molecules affecting the function of RBPs have been developed, providing new avenues for drug discovery. Herein, we describe the perspectives on developing small molecule regulators of RBPs. The following types of small molecule modulators are of great interest in drug discovery: small molecules binding to RBPs to affect interactions with RNA molecules, bifunctional molecules binding to RNA or RBP to influence their interactions, and other types of molecules that affect the stability of RNA or RBPs. Moreover, we emphasize that the bifunctional molecules may play important roles in small molecule development to overcome the challenges encountered in the process of drug discovery.
Topics: RNA-Binding Proteins; RNA; Drug Discovery
PubMed: 37519019
DOI: 10.1002/1873-3468.14710 -
Small (Weinheim An Der Bergstrasse,... Sep 2023Clustered regularly interspaced short palindromic repeats (CRISPR) and polymerases are powerful enzymes and their diverse applications in genomics, proteomics, and... (Review)
Review
Clustered regularly interspaced short palindromic repeats (CRISPR) and polymerases are powerful enzymes and their diverse applications in genomics, proteomics, and transcriptomics have revolutionized the biotechnology industry today. CRISPR has been widely adopted for genomic editing applications and Polymerases can efficiently amplify genomic transcripts via polymerase chain reaction (PCR). Further investigations into these enzymes can reveal specific details about their mechanisms that greatly expand their use. Single-molecule techniques are an effective way to probe enzymatic mechanisms because they may resolve intermediary conformations and states with greater detail than ensemble or bulk biosensing techniques. This review discusses various techniques for sensing and manipulation of single biomolecules that can help facilitate and expedite these discoveries. Each platform is categorized as optical, mechanical, or electronic. The methods, operating principles, outputs, and utility of each technique are briefly introduced, followed by a discussion of their applications to monitor and control CRISPR and Polymerases at the single molecule level, and closing with a brief overview of their limitations and future prospects.
Topics: CRISPR-Cas Systems; Clustered Regularly Interspaced Short Palindromic Repeats; Gene Editing; Biotechnology
PubMed: 37226388
DOI: 10.1002/smll.202300328 -
Small (Weinheim An Der Bergstrasse,... Apr 2024Autophagy, vital for removing cellular waste, is triggered differently by small molecules and nanoparticles. Small molecules, like rapamycin, non-selectively activate... (Review)
Review
Autophagy, vital for removing cellular waste, is triggered differently by small molecules and nanoparticles. Small molecules, like rapamycin, non-selectively activate autophagy by inhibiting the mTOR pathway, which is essential for cell regulation. This can clear damaged components but may cause cytotoxicity with prolonged use. Nanoparticles, however, induce autophagy, often causing oxidative stress, through broader cellular interactions and can lead to a targeted form known as "xenophagy." Their impact varies with their properties but can be harnessed therapeutically. In this review, the autophagy induced by nanoparticles is explored and small molecules across four dimensions: the mechanisms behind autophagy induction, the outcomes of such induction, the toxicological effects on cellular autophagy, and the therapeutic potential of employing autophagy triggered by nanoparticles or small molecules. Although small molecules and nanoparticles each induce autophagy through different pathways and lead to diverse effects, both represent invaluable tools in cell biology, nanomedicine, and drug discovery, offering unique insights and therapeutic opportunities.
PubMed: 38616767
DOI: 10.1002/smll.202310966 -
Trends in Pharmacological Sciences May 2024RNA has diverse cellular functionality, including regulating gene expression, protein translation, and cellular response to stimuli, due to its intricate structures.... (Review)
Review
RNA has diverse cellular functionality, including regulating gene expression, protein translation, and cellular response to stimuli, due to its intricate structures. Over the past decade, small molecules have been discovered that target functional structures within cellular RNAs and modulate their function. Simple binding, however, is often insufficient, resulting in low or even no biological activity. To overcome this challenge, heterobifunctional compounds have been developed that can covalently bind to the RNA target, alter RNA sequence, or induce its cleavage. Herein, we review the recent progress in the field of RNA-targeted heterobifunctional compounds using representative case studies. We identify critical gaps and limitations and propose a strategic pathway for future developments of RNA-targeted molecules with augmented functionalities.
Topics: Humans; RNA; Small Molecule Libraries; Animals
PubMed: 38641489
DOI: 10.1016/j.tips.2024.03.006 -
International Journal of Molecular... Jun 2024Triple-negative breast cancer (TNBC) cells are devoid of estrogen receptors (ERs), progesterone receptor (PRs), and human epidermal growth factor receptor 2 (HER2), and... (Review)
Review
Triple-negative breast cancer (TNBC) cells are devoid of estrogen receptors (ERs), progesterone receptor (PRs), and human epidermal growth factor receptor 2 (HER2), and it (TNBC) counts for about 10-15% of all breast cancers. TNBC is highly invasive, having a faster growth rate and a higher risk of metastasis and recurrence. Still, chemotherapy is one of the widely used options for treating TNBC. This study reviewed the histological and molecular characterization of TNBC subtypes, signaling pathways that are aberrantly expressed, and small molecules targeting these pathways, as either single agents or in combination with other therapeutic agents like chemotherapeutics, immunotherapeutics, and antibody-drug conjugates; their mechanisms of action, challenges, and future perspectives were also reviewed. A detailed analytical review was carried out using the literature collected from the SciFinder, PubMed, ScienceDirect, Google Scholar, ACS, Springer, and Wiley databases. Several small molecule inhibitors were found to be therapeutics for treating TNBC. The mechanism of action and the different signaling pathways through which the small molecules exert their effects were studied, including clinical trials, if reported. These small molecule inhibitors include buparlisib, everolimus, vandetanib, apatinib, olaparib, salidroside, etc. Some of the signaling pathways involved in TNBC, including the VEGF, PARP, STAT3, MAPK, EGFR, P13K, and SRC pathways, were discussed. Due to the absence of these biomarkers, drug development for treating TNBC is challenging, with chemotherapy being the main therapeutic agent. However, chemotherapy is associated with chemoresistance and a high toxicity to healthy cells as side effects. Hence, there is a continuous demand for small-molecule inhibitors that specifically target several signaling pathways that are abnormally expressed in TNBC. We attempted to include all the recent developments in this field. Any omission is truly unintentional.
Topics: Humans; Triple Negative Breast Neoplasms; Female; Antineoplastic Agents; Signal Transduction; Molecular Targeted Therapy; Small Molecule Libraries
PubMed: 38892472
DOI: 10.3390/ijms25116285 -
Small (Weinheim An Der Bergstrasse,... Feb 2024Resolution control and expansibility have always been challenges to the fabrication of structural color materials. Here, a facile strategy to print cholesteric liquid...
Resolution control and expansibility have always been challenges to the fabrication of structural color materials. Here, a facile strategy to print cholesteric liquid crystal elastomers (CLCEs) into complex structural color patterns with variable resolution and enhanced expansibility is reported. A volatile solvent is introduced into the synthesized CLC oligomers, modifying its rheological properties and allowing direct-ink-writing (DIW) under mild conditions. The combination of printing shear flow and anisotropic deswelling of ink drives the CLC molecules into an ordered cholesteric arrangement. The authors meticulously investigate the influence of printing parameters to achieve resolution control over a wide range, allowing for the printing of multi-sized 1D or 2D patterns with constant quality. Furthermore, such solvent-cast direct-ink-writing (DIW) strategy is highly expandable and can be integrated easily into the DIW of bionic robots. Multi-responsive bionic butterfly and flower are printed with biomimetic in both locomotion and coloration. Such designs dramatically reduced the processing difficulty of precise full-color printing and expanded the capability of structural color materials to collaborate with other systems.
PubMed: 37759391
DOI: 10.1002/smll.202306646 -
Small (Weinheim An Der Bergstrasse,... Jun 2024The progression of self-powered micro/-nanomotors (MNMs) has rapidly evolved over the past few decades, showing applications in various fields such as nanotechnology,... (Review)
Review
The progression of self-powered micro/-nanomotors (MNMs) has rapidly evolved over the past few decades, showing applications in various fields such as nanotechnology, biomedical engineering, microfluidics, environmental science, and energy harvesting. Miniaturized MNMs transduce chemical/biochemical energies into mechanical motion for navigating through complex fluidic environments with directional control via external forces fields such as magnetic, photonic, and electric stimuli. Among various propulsion mechanisms, buoyancy-driven MNMs have received noteworthy recognition due to their simplicity, efficiency, and versatility. Buoyancy force-driven motors harness the principles of density variation-mediated force to overcome fluidic resistance to navigate through complex environments. Restricting the propulsion in one direction helps to control directional movement, making it more efficient in isotropic solutions. The changes in pH, ionic strength, chemical concentration, solute gradients, or the presence of specific molecules can influence the motion of buoyancy-driven MNMs as evidenced by earlier reports. This review aims to provide a fundamental and detailed analysis of the current state-of-the-art in buoyancy-driven MNMs, aiming to inspire further research and innovation in this promising field.
PubMed: 38225699
DOI: 10.1002/smll.202308580 -
Small (Weinheim An Der Bergstrasse,... Oct 20232D nanosheets self-assembled with amphiphilic molecules are promising tools for biomedical applications; yet, there are challenges to form and stabilize these nanosheets...
2D nanosheets self-assembled with amphiphilic molecules are promising tools for biomedical applications; yet, there are challenges to form and stabilize these nanosheets under complex physiological conditions. Here, the development of lipid nanosheets with high structural stability that can be reversibly converted to cell-sized vesicles by changes in pH within the physiological range robustly, are described. The system is controlled by the membrane disruptive peptide E5 and a cationic copolymer anchored on lipid membranes. It is envisioned that nanosheets formed using the dual anchoring peptide/cationic copolymer system can be employed in dynamic lipidic nanodevices, such as the vesosomes described here, drug delivery systems, and artificial cells.
Topics: Peptides; Drug Delivery Systems; Polymers; Hydrogen-Ion Concentration; Lipids
PubMed: 37376845
DOI: 10.1002/smll.202301219 -
Drug Discovery Today May 2024Transient receptor potential canonical (TRPC) channels belong to an important class of non-selective cation channels. This channel family consists of multiple members... (Review)
Review
Transient receptor potential canonical (TRPC) channels belong to an important class of non-selective cation channels. This channel family consists of multiple members that widely participate in various physiological and pathological processes. Previous studies have uncovered the intricate regulation of these channels, as well as the spatial arrangement of TRPCs and the binding sites for various small molecule compounds. Multiple small molecules have been identified as selective agonists or inhibitors targeting different subtypes of TRPC, including potential preclinical drug candidates. This review covers recent advancements in the understanding of TRPC regulation and structure and the discovery of TRPC small molecules over the past few years, with the aim of facilitating research on TRPCs and small-molecule drug discovery.
Topics: Humans; Animals; Transient Receptor Potential Channels; Drug Discovery; Small Molecule Libraries
PubMed: 38514041
DOI: 10.1016/j.drudis.2024.103951