RNA

RNA is crucial for the regulation of numerous cellular processes and functions. With the in-depth study of disease mechanisms, processes such as RNA expression, splicing, translation, and stability regulation have become new targets for disease intervention. RNA has provided new therapeutic modalities for metabolic diseases, genetic disorders, and cancer patients, resulting in several innovative drugs.

MCE R&D team collected small molecules targeting RNA from the PDB, R-BIND, ROBIN, and internal database as the positive dataset, and non-targeting RNA small molecules from ROBIN as the negative dataset. Based on the GeminiMol pre-trained model, we encoded the molecules and calculated over 1700 molecular descriptors using Mordred as inputs for the model. Subsequently, we employed 13 deep learning models to learn from the data. All of which yielded good training results, with AUROCs greater than 0.75. Ultimately, we selected the Finetune model to screen HY-L901P, which exhibited the best classification performance, achieving an AUROC of 0.82 and a prediction accuracy of 0.76. We then applied filtering based on StaR rules (with at least two of the following properties: cLogP ≥ 1.5, Molar Refractivity ≥ 4, Relative Polar Surface Area ≤ 0.3) to obtain a library containing approximately 5,000 small molecule compounds targeting RNA. This library serves as a valuable tool for screening small molecules that interact with RNA.

Macrocycles are promising scaffolds for the design of novel RNA targeting molecules. This collection of macrocycles for RNA consists of very diverse, drug-like molecules which incorporate certain known RNA-recognition elements (e.g. nucleobase ring systems and analogs) distributed within macrocyclic rings or peripheral fragments. As macrocyclic molecules tend to be larger than traditional screening molecules, it is vital to carefully assess and control their physicochemical properties. All macrocycles have been tested for aqueous and DMSO solubility with cutoffs applied at 10 mM in DMSO and 50 µM in PBS (pH 7.4); PAMPA permeability has also been tested for representative set of macrocycles.

Hepatitis C virus (HCV) is a hepatotropic enveloped positive- strand RNA virus (family Flaviviridae) that infects the parenchymal cells of the liver. HCV infection is a significant public health burden. Globally, an estimated 71 million people have chronic hepatitis C virus infection. A significant number of those who are chronically infected will develop cirrhosis or liver cancer. To date, there is no vaccine against HCV, and combination pegylated alpha interferon (pIFN-) and ribavirin, the main standard-of-care treatment for HCV, is effective in only a subset of patients and is associated with a wide spectrum of toxic side effects and complications. More recently, new therapeutic approaches that target essential components of the HCV life cycle have been developed, including direct-acting antiviral (DAA) that specifically block a viral enzyme or functional protein and host-targeted agents (HTA) that block interactions between host proteins and viral components that are essential to the viral life cycle. However, the genetic diversity of HCV viruses and the stage of liver disease (i.e., cirrhosis) are revealing themselves as obstacles for effective, pan-genotypic treatments. There still exists a need for the discovery and development of new HCV inhibitors. In particular, since the future of HCV therapy will likely consist of a cocktail approach using multiple inhibitors that target different steps of infection, new antivirals targeting all steps of the viral infection cycle.

MCE offers a unique collection of 349 compounds with identified and potential anti-HCV activity. MCE Anti- Hepatitis C Virus Compound Library is a useful tool for discovery new anti-HCV drugs and other anti-infection research.

Nucleoside and nucleotide analogues are synthetic, chemically modified compounds that have been developed to mimic their physiological counterparts in order to exploit cellular metabolism and subsequently be incorporated into DNA and RNA to inhibit cellular division and viral replication. In addition to their incorporation into nucleic acids, nucleoside and nucleotide analogues can interact with and inhibit essential enzymes such as human and viral polymerases (that is, DNA-dependent DNA polymerases, RNA-dependent DNA polymerases or RNA-dependent RNA polymerases), kinases, ribonucleotide reductase, DNA methyltransferases, purine and pyrimidine nucleoside phosphorylase and thymidylate synthase. These actions of nucleoside and nucleotide analogues have potential therapeutic benefits — for example, in the inhibition of cancer cell growth, the inhibition of viral replication as well as other indications.

MCE offers a unique collection of 562 nucleotide compounds including nucleotide, nucleoside and their structural analogues. MCE Nucleotide Compound Library is a useful tool to discover anti-cancer and antiviral drugs for high throughput screening (HTS) and high content screening (HCS).

Mitochondria, as the main place of energy supply in life, is essential to maintain normal life activities. Mitochondrial dysfunction is associated with common diseases, such as cardiovascular diseases, neurodegenerative diseases, diabetes and cancer. The heart, brain and liver rely heavily on mitochondrial function as the main organs for drug metabolism. In addition, mitochondria is also a target of many drugs, some of which induce organotoxicity by inducing mitochondrial toxicity.

MCE contains 507 mitochondrial toxic compounds, which can be used as tool compounds for drug development and disease mechanism research.

DNA is prone to numerous forms of damage that can injure cells and impair fitness. Cells have developed an array of mechanisms to repair these injuries. Proliferating cells are especially vulnerable to DNA damage due to the added demands of cellular growth and division. Cell cycle checkpoints represent integral components of DNA repair that coordinate cooperation between the machinery of the cell cycle and several biochemical pathways that respond to damage and restore DNA structure. By delaying progression through the cell cycle, checkpoints provide more time for repair before the critical phases of DNA replication, when the genome is replicated, and of mitosis, when the genome is segregated. Loss or attenuation of checkpoint function may increase spontaneous and induced gene mutations and chromosomal aberrations by reducing the efficiency of DNA repair.

MCE owns a unique collection of 2,713 cell cycle/DNA damage-related compounds which can be used in the research of the same.

Epigenetics refers to changes in phenotype that are not rooted in DNA sequence. Many types of epigenetic processes have been identified, including DNA methylation, alteration in the structure of histone proteins and gene regulation by small noncoding microRNAs. Modification of DNA, protein, or RNA, resulting in changes to the function and/or regulation of these molecules, without altering their primary sequences, reveals the complexities of cellular differentiation, embryology, the regulation of gene expression, aging, cancer, and other diseases.

MCE provide a unique collection of 1,630 epigenetics-related compounds that can be used in the research of the related diseases.

According to reports, most known kinase inhibitors exert their effects through competitive binding in highly conserved ATP pockets. Although genetic techniques such as RNA interference can inactivate specific genes, most kinases are multi domain proteins, each of which has an independent function. Highly selective inhibitors have higher efficiency than non-selective inhibitors, and the selectivity to the target is at least 100 times higher. Therefore, ensuring the validation of targets with the most selective inhibitors is crucial for a more thorough understanding of the pharmacology of the kinase field. The Highly Selective Inhibitors Library contains 5,433 compounds, covering multiple targets and subtypes, such as GPCR protein family, Ion channel, multiple kinases, etc. The Highly Selective Inhibitors Library is an effective tool for screening different phenotypes

Transcription is the essential first step in the conversion of the genetic information in the DNA into protein and the major point at which gene expression is controlled. Transcription of protein-coding genes is accomplished by the multi-subunit enzyme RNA polymerase II and an ensemble of ancillary proteins, called transcription factors (TFs). Transcription factors play an important role in the long-term regulation of cell growth, differentiation and responses to environmental cues. Deregulated transcription factors contribute to the pathogenesis of a plethora of human diseases, ranging from diabetes, inflammatory disorders and cardiovascular disease to many cancers, and thus these proteins hold great therapeutic potential.

MCE offers a unique collection of 1,879 compounds with validated transcription factor targets modulating properties. MCE transcription factor-targeted compound library is an effective tool for researching transcription factors as drug targets as well as modulation of TFs for different therapeutic applications.

The high rates of morbidity and mortality caused by fungal infections are associated with the current limited antifungal arsenal and the high toxicity of the compounds. Additionally, identifying novel drug targets is challenging because there are many similarities between fungal and human cells. The most common antifungal targets include fungal RNA synthesis and cell wall and membrane components, though new antifungal targets are being investigated. Nonetheless, fungi have developed resistance mechanisms, such as overexpression of efflux pump proteins, overexpression and changes in drug targets and biofilm formation, emphasizing the importance of discovering new antifungal drugs and therapies. Due to the limited antifungal arsenal, researchers have sought to improve treatment via different approaches, such as the combination of antifungal drugs, development of new formulations for antifungal agents and modifications to the chemical structures of traditional antifungals, etc.

MCE offers a unique collection of 437 compounds with validated antifungal activities. MCE antifungal compound library is an effective tool for drug repurposing screening, combination screening and biological investigation.

RNase R is a magnesium ion-dependent 3'-5' exoribonuclease that can increase the abundance of circular RNA by degrading linear RNA in mixed RNA, thereby enriching circular RNA.

RNase H is an endoribonuclease expressed and purified from Escherichia coli and can specifically hydrolyze RNA in DNA-RNA hybrid strands.

MCE In vivo OptiLNP RNA Transfection Reagent (Systemic Effect) is a ready-to-use transfection reagent based on LNP technology. It is designed for the efficient transfection of mRNA and short-chain RNA in experimental animals. The RNA functions systemically.

MCE In vivo OptiLNP RNA Transfection Reagent (Local Effect) is a ready-to-use transfection reagent based on LNP technology. It is designed for the efficient transfection of mRNA and short-chain RNA in experimental animals. The RNA functions locally.

MCE OptiLNP RNA Transfection Reagent (Stem Cells) is a ready-to-use transfection reagent based on LNP technology. It is designed for the efficient transfection of various RNA types into stem cells.

MCE OptiLNP RNA Transfection Reagent (Immune Cells) is a ready-to-use transfection reagent based on LNP technology. It is designed for the efficient transfection of various RNA types into immune cells.

MCE OptiLNP Short-Chain RNA Transfection Reagent is a ready-to-use transfection reagent based on LNP technology. It is designed for the efficient transfection of short-chain RNA into common cells.

MCE OptiLNP RNA Transfection Reagent (Primary Immune Cells) is a ready-to-use transfection reagent based on LNP technology. It is designed for the efficient transfection of various RNA types into primary immune cells.

MCE In vivo OptiLNP RNA Transfection Reagent (Lung-targeted) is a ready-to-use transfection reagent based on LNP technology. It is designed for the efficient transfection of mRNA and short-chain RNA via intravenous injection in experimental animals.

MCE OptiLNP RNA Transfection Reagent is a ready-to-use transfection reagent based on LNP technology. It is designed for the efficient transfection of various RNA types into common cells.

MCE In vivo OptiLNP RNA Transfection Reagent (Liver-targeted) is a ready-to-use transfection reagent based on LNP technology. It is designed for the efficient transfection of mRNA and short-chain RNA via intravenous injection in experimental animals.

MCE HP PolyFast Transfection Reagent is a novel cationic polymer transfection reagent for DNA and RNA transfection.

FnCas12a(Cpf1), is an RNA-guided, DNA-editable recombinant endonuclease that can be used for gene editing and detection.

MCE MCE Reverse Transcription Kit III is suitable for the conventional synthesis of cDNA from RNA and the stem-loop method for the synthesis of cDNA from microRNA (miRNA).

MCE PolyFast Transfection Reagent consists of cationic polymers and can introduce nucleic acids (DNA or RNA) into eukaryotic cells efficiently, including some hard-to-transfect cells.

MCE Agarose can be made into 0.5-2.5% agarose gel according to different needs and can resolve DNA and RNA fragments from 50-15,000 bp.

MCE Oligo (dT)₃₀ Magnetic Beads are designed for the rapid isolation of highly purified, intact mRNA from eukaryotic total RNA or directly from crude extracts of cells, plant and animal tissues.

MCE T4 DNA Ligase (Fast) is produced by Escherichia coli carrying a T4 phage, catalyzes the formation of a phosphodiester bond between juxtaposed 5'-phosphate and 3'-hydroxyl termini in duplex DNA or RNA.

MCE RT Master Mix for qPCR II is a convenient, ready-to-use formulation for reverse transcription and can eliminate genomic DNA (gDNA) contaminations in RNA samples. With updated reverse transcriptase, this kit can synthesize cDNA more rapidly, more specifically.

MCE RT Master Mix for qPCR (gDNA digester plus) is a convenient, ready-to-use formulation for reverse transcription and can eliminate genomic DNA (gDNA) contaminations in RNA samples. The cDNA product can be directly applied as a template in a standard PCR and real time quantitative PCR (qPCR).