small-molecule blocker

Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecular targets that are involved in the growth, progression, and spread of cancer.

There are several different types of targeted therapy. The most common types are small-molecule drugs and monoclonal antibodies. Small-molecule drugs are small enough to enter cells easily, so they are used for targets that are inside cells, while monoclonal antibodies are usually used for targets that are located outside the cells. Because of high specificity, low side effect and potent anticancer activity, targeted therapy has become the mainstream of new anti-tumor drugs. Various targeted therapies have been approved by FDA and used in the treatment of diseases.

MCE carefully collects a unique of 108 targeted therapy drugs used in cancer treatment. MCE Targeted therapy drug library is a useful tool for the research of targeted therapy.

With the aging population and increasing competitive pressures, neurodegenerative diseases of the central nervous system (CNS) have become a serious medical challenge in modern society, including Parkinson's disease, Alzheimer's disease, brain tumors, and multiple sclerosis. However, the success rate of CNS drug development remains remarkably low, primarily due to the blood-brain barrier (BBB). The blood-brain barrier (BBB) is a semipermeable barrier structure that surrounds the microvasculature of the CNS. In capillaries, the wedged endothelial cells are tightly packed and wedge-shaped, lining the interior of the vessels to form extensive tight junctions. Along with a range of receptors, transporters, efflux pumps, and other cellular components, this barrier regulates the entry and exit of molecules between the bloodstream and the brain. The intact BBB blocks the passage of most blood-borne substances into the brain, preventing nearly 100% of large-molecule drugs and over 98% of small-molecule drugs from entering. Compared to non-CNS drugs, physicochemical properties such as hydrogen bonds, lipophilicity, and molecular weight significantly influence a compound's ability to cross the BBB. Using artificial intelligence (AI) algorithms to predict BBB permeability, a predicted value greater than 0.75 indicates that the compound has strong potential to cross the BBB, providing a promising starting point for CNS drug discovery.

In drug discovery and development (R&D) area, target binding and druggability optimization are core processes. Among these attributes, high solubility is critical for a compound to achieve druggability, as it directly impacts the progress of drug R&D. Superior solubility ensures the rapid dissolution and uniform distribution of drug molecules in vivo, thereby enhancing bioavailability and effectively mitigating issues such as suboptimal efficacy, increased dosage requirements, or exacerbated toxic and side effects arising from insufficient solubility.

From the perspective of medicinal chemistry, high-solubility drug fragments serve as high-quality "molecular building blocks". Based on these fragments, lead compounds with potential druggability can be rapidly screened out, which significantly shortens the drug R&D cycle and reduces R&D costs. Meanwhile, the high-solubility drug fragment library can provide diverse options for drug development in different therapeutic areas, offer solutions for the solubility defects of existing clinical drugs, and facilitate the development of novel, highly effective targeted drugs with higher bioavailability and better safety profiles.

MCE has collected and compiled 2,527 experimentally validated small-molecule fragments with high solubility. These fragments can be directly used for drug molecular design, providing high-quality pre-validated solubility fragments that significantly improve the efficiency of lead compound screening and accelerate the progress of drug R&D.

Owing to the widespread transmission and frequent mutation of viral diseases, as well as the continuous emergence of new viruses and drug-resistant strains, antiviral drug development is facing increasingly stringent requirements. Antiviral compound libraries serve as important tools for drug screening, mechanism research and development, enabling the discovery and investigation of various antiviral drugs.

These compounds act through diverse antiviral mechanisms, targeting key steps in viral replication, assembly and invasion. They exert antiviral effects by inhibiting viral nucleic acid synthesis, blocking viral protein processing, and preventing viral binding to host cells. This library covers various types of antiviral compounds, including nucleosides, non-nucleosides, protease inhibitors and integrase inhibitors. It supports research on influenza virus, herpes virus, hepatitis virus, emerging respiratory viruses and other pathogens, and enables high-throughput screening of novel antiviral candidates to rapidly identify potential active compounds against diverse viruses. It also facilitates mechanistic studies to elucidate drug-target interactions and viral resistance mechanisms, and supports the screening of effective compounds against mutant strains for research on viral variation and drug resistance.

This antiviral library consists of 6,804 compounds with lead-like physicochemical properties. The core sources of the compounds include analogs of known antiviral molecues with a similarity score ≥ 0.6. MCE has collected more than 1450 antiviral molecules. As a small-molecule collection with both activity potential and structural modifiability, it provides strong support for antiviral drug research and development.

Kinases is a class of enzymes that adds chemicals called phosphates to other molecules, such as sugars or proteins. Protein phosphorylation serves as a critical regulatory mechanism for numerous cellular processes including cell division, metabolism, and signal transduction, with approximately 50% of cellular functions in humans being regulated by kinase activity. In drug discovery, kinases represent a major category of therapeutic targets, and kinase inhibitors constitute an important class of pharmaceuticals that block the activity of specific disease-associated enzymes, particularly in cancer and inflammatory disorders. Small molecule kinase inhibitors represent one of the fastest-growing drug categories, having received U.S. Food and Drug Administration (FDA) approval for both oncological and non-oncological indications. As of September 2023, over 70 FDA-approved small molecule kinase inhibitors are commercially available.

The MCE Kinase Inhibitor Library Mini contains 270 kinase inhibitors primarily targeting protein kinases (VEGFR, EGFR, BTK, CDK, Akt, etc.), lipid kinases (PI3K, PI4K, SK, etc.), and carbohydrate kinases. This collection includes 1-3 highly specific representative compounds per target, optimized for screening of kinase-related drug targets in pharmaceutical research.

Amino acids, as one of the most fundamental organic compounds in living organisms, serve not only as the basic building blocks of proteins but also but also undertake the functions of energy supply, neurotransmitter synthesis, and maintenance of internal environment stability.Amino acid metabolic enzymes are a class of enzymes involved in the metabolic processes of amino acids, catalyzing their synthesis, breakdown, transformation, and interactions with other metabolic pathways. Abnormalities in amino acid metabolic enzymes can lead to various metabolic diseases, such as phenylketonuria and hyperammonemia, etc. Therefore, actively exploring and regulating the processes of amino acid metabolism is crucial for the development of drugs related to these diseases.

MCE designs a unique collection of 335 small molecules target amino acid metabolizing enzymes, which is an important tool for studying studying amino acid metabolism processes or metabolism-related drug development.

Cyclic peptide library have advantages such as high affinity, high selectivity, and suitability for targeting protein–protein interactions. Through DEL synthesis technology, the library size can achieve hundreds of millions. DEL cyclic peptide library have advantages like low cost andhigh screeing efficiency, making them valuable for discovering lead compounds against challenging drug targets.

This cyclic peptide library is constructed with unnatural amino acids as building block, synthesized through DNA-compatible chemical reactions. Each cyclic peptide consist of six amino acids and constrained conformations such as side-chain cross-linking, disulfide bonds, and macrocyclization. These cyclic peptides exhibit significantly improved stability and druggability compared with linear peptides, filling the gap between small molecules and macromolecular biologics. Each cyclic peptide is uniquely conjugated to a DNA barcode sequence for molecular identification and sequencing decoding.

MCE’s cyclic peptide library has8 independent sub-libraries, with a total molecular diversity of 1.2 billion. It is constructed via multi-round combinatorial assembly of building blocks and diverse cyclization strategies, facilitating the discovery of cyclic peptide leads for undruggable targets.

Covalent inhibitors are small molecules that can bind specifically to target proteins through covalent bonds and inhibit their biological functions. Although for a long time, covalent targeting has been playing a subordinate role in drug discovery, with an increasing number of reports on successful clinical applications of such drugs, the potential of these agents is now being acknowledged. Currently, cysteine is the most common covalent amino acid residue in a variety of covalent drugs, and various warheads have been developed that can react with cysteine, providing the key building blocks for covalent drugs to form covalent bonds.

To meet the development needs of covalent inhibitors targeting cysteine, MCE has designed a unique collection of 5,112 compounds with different covalent warheads that target cysteine. The MCE Cysteine Targeted Covalent Library is designed using the following covalent warheads: Acrylamides, Propiolic acid ester, Dimethylamine functionalized acrylamides, Chloroacetamides, Acrylonitrile, 2-Cyanoacrylamide, Aziridine, Haloacetamide, etc.

Covalent inhibitors are small molecules that can bind specifically to target proteins through covalent bonds and inhibit their biological functions. Although for a long time, covalent targeting has been playing a subordinate role in drug discovery, with an increasing number of reports on successful clinical applications of such drugs, the potential of these agents is now being acknowledged. Currently, cysteine is the most common covalent amino acid residue in a variety of covalent drugs, and various warheads have been developed that can react with cysteine, providing the key building blocks for covalent drugs to form covalent bonds.

To meet the development needs of covalent inhibitors targeting cysteine, MCE has designed a unique collection of 3,601 fragments with different covalent warheads that target cysteine. The MCE Cysteine Targeted Covalent Fragment Library is designed using the following covalent warheads: Acrylamides, Propiolic acid ester, Dimethylamine functionalized acrylamides, Chloroacetamides, Acrylonitrile, 2-Cyanoacrylamide, Aziridine, Haloacetamide, etc. All fragments are pre-filtered with the Rule of Three restrictions which can be used for fragment-based covalent drug development.

Peptides, composed of amino acids, serve as crucial building blocks for proteins and have gained significant attention in drug development over the past decade. The advancements in production, modification, and analytical technologies have led to a surge in the potential applications of peptides in medicine. Peptides offer a number of advantages over small molecule drugs, including: greater target specificity and efficacy, more predictable metabolic profiles, easier delivery to where they are needed in the body, and fewer side effects. Peptides are increasingly appearing in all branches of medicine as components of innovative drugs, imaging agents, diagnostic agents, and other complex drugs such as peptide-drug conjugates. To date, more than 80 peptide drugs have been approved to treat a variety of diseases, including microbial infections, obesity, anti-diabetes, and cancer, as well as to develop cell targeting platforms and improve cell penetration properties.

MCE designs a unique collection of 826 peptide compounds. HY-L105S is a peptide compound library that can be provided with solution form based on HY-L105, and can be applied to peptides-based drug development.