biologically toxic

Unlike the 20 natural amino acids commonly found within living organisms, non-natural amino acids are synthesized through chemical or biosynthetic methods, thereby being endowed with unique chemical properties or biological activities. In drug development, these amino acids can be utilized to design novel pharmaceutical molecules that may exhibit superior pharmacological characteristics, such as increased selectivity, improved pharmacokinetic profiles, or reduced toxicity. In biomedical research, uon-natural amino acids can act as biological markers or probes for investigating biological processes like cell signaling, protein conformation, and protein-protein interactions. In addition, non-natural amino acids can also be used in the field of agriculture to develop new pesticides, plant growth regulators and so on.

Antimicrobial Peptides (AMPs), also known as antimicrobial peptides or antibiotic peptides, are a class of polypeptides encoded by specific genes in various biological cells and induced by external stimuli. They exhibit broad-spectrum bioactivity against bacteria, fungi, viruses, protozoa, and even tumor cells. AMPs serve as crucial effector molecules in the host's innate immune system.Due to their wide antimicrobial spectrum, low toxicity to normal cells of higher animals, high safety profile, low tendency to induce resistance, and additional benefits such as immune enhancement and antioxidant effects, antimicrobial peptides hold significant promise in new drug development.

MCE offers 58 types of antimicrobial peptides, which can be applied in high-throughput screening for research in anti-infection therapies, immunotherapy, anticancer drug development, and agricultural disease control.

Boric acid is a stable and usually non-toxic group widely used in modern synthesis to form C-C and C-heteroatom bonds. Boric acid exhibits exquisite reversible coordination characteristics and can be explored as a molecular construction tool, with specific mechanisms for controlling the structure and biological characteristics of bioconjugates. Boric acid has various activities, such as anticancer, antibacterial, and antiviral activities. In drugs, boric acid mainly exists in the form of arylboronic acid. In addition to this form, heterocycles containing boric acid, such as pyridine, pyrrole, and indole derivatives, are also very useful in pharmaceutical chemistry. Molecular modification by introducing boric acid groups into bioactive molecules has been shown to alter selectivity, physicochemical, and pharmacokinetic characteristics, and improve existing activity.

MCE designs a unique collection of 163 boronic acid compounds. It is a good tool to be used for research on cancer and other diseases.

Withdrawal or delisting drugs refer to drugs that are recalled or discontinued from the market due to low efficiency, serious side effects, financial and regulatory problems and other reasons. Once the drug is withdrawn from the market, it will cause heavy losses to the original research company that invested a lot of time, finance and other costs to develop the drug.

Adverse drug reaction (ADR) is the main reason for drug withdrawal from the market. ADR refers to the unexpected effects caused by the reasons such as the target-directed interaction during the treatment. However, studying the mechanism of these ADRs may just be a breakthrough in finding new indications. For example, thalidomide, the protagonist of the drug damage event that caused numerous "seal babies" deformed infants, was found to be due to the degradation of a transcription factor - SALL4 after delisting, which made thalidomide have a new clinical application. In 1998, it was approved by FDA for the treatment of leprosy nodular erythema, and in 2006, it was approved for the treatment of multiple myeloma. ADR study of delisted drugs can not only avoid the loss of drug development in advance but also bring hope to new indications.

MCE has sorted out 230 drug compounds withdrawn from the market through FDA, EMA and other authoritative platforms. Each compound has withdrawal records in at least one country/market. It is a useful tool for conducting research on drug side effects or drug toxicity mechanisms and discovering new indications of drugs.

Cyclic peptides are polypeptide chains taking cyclic ring structure, which exhibit diverse biological activities, such as antibacterial activity, immunosuppressive activity and anti-tumor activity. Cyclic peptides, with the features of good binding affinity, target selectivity and low toxicity, show great success as therapeutics. Multiple cyclic peptides are currently in clinical use, for examples, gramicidin and tyrocidine with bactericidal activity, cyclosporin A with immunosuppressive activity, and vancomycin with antibacterial activity. Furthermore, cyclic peptides usually have the sufficient size and a balanced conformational flexibility/rigidity for binding to flat protein-protein interaction (PPI) interfaces, which have potential to develop PPI drugs.

MCE offers a unique collection of 97 cyclic peptides, all of which have good bioactivities. MCE Cyclic Peptide Library is a powerful tool for drug discovery and PPI inhibitor screening.

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 551 compounds with validated antifungal activities. MCE antifungal compound library is an effective tool for drug repurposing screening, combination screening and biological investigation.

Biotoxins, also referred to as natural toxins, are chemical substances produced by plants, animals, or microorganisms that exert toxic effects on other living organisms. Due to unique biological activities, biotoxins have been widely applied in molecular biology, physiology, pharmacology, and the clinical diagnosis and treatment of various human diseases, becoming an important source of natural drug development. Biotoxins can specifically bind to and interfere with intracellular signaling molecules or receptors, thereby altering cellular signaling processes. Leveraging this characteristic, biotoxins can be used to study the regulatory mechanisms of cellular signaling pathways. For example, neurotoxins such as snake venom peptides can be used to investigate the functional regulation of neurotransmitter receptors and ion channels. Additionally, biotoxins have demonstrated significant potential in drug development across various fields, including neurological diseases, cardiovascular diseases, anticoagulation, and anti-cancer therapies. With advancements in high throughput screening, structural optimization, and antibody-toxin conjugation technologies, numerous biotoxins or their structural analogs have been successfully brought to market, such as Ziconotide, Captopril, Bivalirudin, and Eptifibatide.

MCE offers 90 types of biotoxins, including neurotoxins, cardiotoxins, mycotoxins, and more.

Small molecule covalent inhibitors, or irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity, such that covalent warheads can target rare residues of a particular target protein, thus leading to the development of highly selective inhibitors and achieving a more complete and continued target occupancy in living systems. In recent years, the distinct strengths of covalent inhibitors in overcoming drug resistance had been recognized. However, toxicity can be a real challenge related to this class of therapeutics due to their potential for off-target reactivity and has led to these drugs being disfavored as a drug class. The drug design and optimization of covalent inhibitors has become a hot spot in drug discovery.

MCE covalent inhibitor library contains 1,546 small molecules including identified covalent inhibitors and other bioactive molecules having common covalent reactive groups as warheads, such as acrylamides, activated terminal acetylenes, Sulfonyl fluorides/esters, cloracetamides, alkyl halides, epoxides, aziridines, disulfides, etc.

Copper is an important co-factor of all biological enzymes, but if the concentration exceeds the threshold of maintaining the homeostasis mechanism, copper will lead to cytotoxicity. This death mechanism has been named "Cuproptosis".

The mechanism of cuproptosis distinct from all other known mechanisms of regulated cell death, including apoptosis, pyroptosis, necroptosis, and ferroptosis.

Copper combine with the lipoylated components of the tricarboxylic acid cycle (TCA), leading to lipoylated protein aggregation and subsequent loss of iron-sulfur cluster proteins, ultimately resulting in protein toxicity stress and cell death. Studies have shown that the necessary factors for cuproptosis include the presence of glutathione, mitochondrial metabolism of galactose and pyruvate, and glutamine metabolism.

Targeted regulation of cuproptosis is a potential choice to treat cancer, rheumatoid arthritis, and other diseases. For example, up-regulation of LIPT1 may inhibit the occurrence and development of tumors by destroying TCA in mitochondria and then inducing cuproptosis.

MCE supplies a unique collection of 403 cuproptosis-related compounds, all of which act on the targets or signaling pathways related to cuproptosis and may have in inhibitory or activated effect on cuproptosis. MCE Cuproptosis Library is a useful tool for drug research related to cancer, rheumatoid arthritis, and other diseases.

Small molecule covalent inhibitors, or irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity, such that covalent warheads can target rare residues of a particular target protein, thus leading to the development of highly selective inhibitors and achieving a more complete and continued target occupancy in living systems. In recent years, the distinct strengths of covalent inhibitors in overcoming drug resistance had been recognized. However, toxicity can be a real challenge related to this class of therapeutics due to their potential for off-target reactivity and has led to these drugs being disfavored as a drug class. The drug design and optimization of covalent inhibitors has become a hot spot in drug discovery.

MCE Lead-like Covalent Screening Library offers a valuable resource of 1,049 lead-like compounds with commonly used covalent warheads. These warheads, such as acrylamide, activated terminal alkyne, acyloxymethyl ketone, and boronic acid, are capable of reacting with specific amino acid residues, including cysteine, lysine, serine, and histidine. The inclusion of these reactive warheads in the library allows researchers to explore the potential of covalent inhibition, a powerful approach in drug discovery.

Small molecule covalent inhibitors, or irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity, such that covalent warheads can target rare residues of a particular target protein, thus leading to the development of highly selective inhibitors and achieving a more complete and continued target occupancy in living systems. In recent years, the distinct strengths of covalent inhibitors in overcoming drug resistance had been recognized. However, toxicity can be a real challenge related to this class of therapeutics due to their potential for off-target reactivity and has led to these drugs being disfavored as a drug class. The drug design and optimization of covalent inhibitors has become a hot spot in drug discovery.

MCE covalent inhibitor library contains 5,994 small molecules including identified covalent inhibitors and other molecules having common covalent reactive groups as warheads, such as acrylamides, activated terminal acetylenes, sulfonyl fluorides/esters, cloracetamides, alkyl halides, epoxides, aziridines, disulfides, etc.

MCE Covalent inhibitor Library plus, with more powerful screening capability, further complement Covalent inhibitor Library (HY-L036) by adding some fragment compounds with covalent warheads.

Macrocyclic compounds (≥12-atom cyclic small molecules/peptides) have unique physicochemical properties. They form preorganized conformations with high binding affinity/selectivity, target traditional small-molecule-inaccessible proteins, and bridge small-molecule drugs and biological agents. As key protein phosphorylation enzymes, kinases are linked to tumors, COPD, etc., and are critical therapeutic targets. Traditional small-molecule kinase inhibitors lack selectivity, causing off-target toxicity, low bioavailability, and acquired resistance. Macrocycles’ semi-rigid structure restricts conformations, boosts binding selectivity, optimizes pharmacokinetics, and makes macrocyclization a core kinase inhibitor optimization strategy.

Thousands of bioactive macrocycles were curated from ChEMBL. Via Transformer, macrocyclization was converted into a chemical language translation task, enabling end-to-end macrocycle generation from linear precursors with simplified inputs. Macformer achieves efficient, automated linear molecule macrocyclization via deep learning; generated macrocycles have diversity, novelty, biocompatibility, and cover broader chemical space.

MCE collected thousands of marketed/clinical kinase inhibitors, using their fragments for macrocyclization to generate derivatives. After evaluating synthetic accessibility and physicochemical properties, a million-scale virtual macrocyclic library was built for kinase-related virtual and AI-driven screening.

Macrocyclic compounds (≥12-atom cyclic small molecules/peptides) have unique physicochemical properties. They form preorganized conformations with high binding affinity/selectivity, target traditional small-molecule-inaccessible proteins, and bridge small-molecule drugs and biological agents. As key protein phosphorylation enzymes, kinases are linked to tumors, COPD, etc., and are critical therapeutic targets. Traditional small-molecule kinase inhibitors lack selectivity, causing off-target toxicity, low bioavailability, and acquired resistance. Macrocycles’ semi-rigid structure restricts conformations, boosts binding selectivity, optimizes pharmacokinetics, and makes macrocyclization a core kinase inhibitor optimization strategy.

Thousands of bioactive macrocycles were curated from ChEMBL. Via Transformer, macrocyclization was converted into a chemical language translation task, enabling end-to-end macrocycle generation from linear precursors with simplified inputs. Macformer achieves efficient, automated linear molecule macrocyclization via deep learning; generated macrocycles have diversity, novelty, biocompatibility, and cover broader chemical space.

MCE collected thousands of marketed/clinical kinase inhibitors, using their fragments for macrocyclization to generate derivatives. After evaluating synthetic accessibility and physicochemical properties, a million-scale virtual macrocyclic library was built for kinase-related virtual and AI-driven screening.