optimization

The MCE 1K Drug Fragment Library consists of 1,168 drug fragments. These drug fragments are derived from 2,946 FDA-approved drug molecules, and fragments from one drug can appear in other drugs, so these fragments are somewhat correlated with good PK/PD properties. Fragment-based screening can reserve enough chemical space for subsequent structural optimization. This compound library is an essential tool for drug screening based on FBDD (Fragment-Based Drug Discovery).

ASINEX has elaborated a library of diverse macrocycles using an effective tool box of synthetic methods. The resulting scaffolds are novel, tremendously diverse, medchem-relevant, macrocyclic frameworks.

Macrocyles tend to be larger than traditional screening molecules which make them perfect discovery tools for targets with shallow or extended binding sites. At the same time, their unique character based on restricted flexibility and ability to form intra-molecular hydrogen bonds allows for design approaches effectively optimizing properties such asaqueous solubility and membrane permeability. Many of these macrocycles have been tested for aqueous and DMSO solubility with cut-offs applied at 10 mM in DMSO and 50 µM in PBS (pH 7.4) followed by PAMPA permeability assay.

Fragment-based drug development (FBDD) is a strategy for drug discovery that can be applied both academically and commercially to enhance the identification of some non-drug targets. Fragment-based drug development has identified low molecular weight molecules (<300 Da) capable of binding to related macromolecules. These fragments can cover a wide chemical space and are easy to optimize later. Currently, several fragment-based drugs have entered clinical trials, of which two drugs, Vemurafenib and Venetoclax, have been approved for marketing.

Based on Tanimoto coefficient, MCE uses similarity algorithm to carefully select 2,299 high-structurally diverse 'RO3' compliant fragment molecules from large-scale fragment molecules, which can be applied to fragment based drug development.

The incidence and significance of central nervous system diseases are increasing at an alarming rate all over the world. Although substantial research efforts have been applied to develop new CNS-active drugs, only a few CNS disorders are addressed satisfactorily, while the remaining ones pose significant clinical challenges. Blood-brain barrier (BBB) permeability is one of the most important limiting factors in the design and development of novel CNS-targeted pharmaceuticals for the treatment of neurological disorders.

Carefully selected from the HTS Compound Collection to meet the parameters optimized for high BBB-permeability, our CNS Focused Screening Library comprising over 30,300 structurally-diverse and potentially CNS-active screening compounds. This original Screening Compound Library is aimed at supporting CNS drug design projects and HTS efforts in search for novel neurotherapeutics.

Fragment-based drug discovery (FBDD) is well suited for discovering both drug leads and chemical probes of protein function. 3-dimensionality (3D) diversity is pivotal because the molecular shape is one of the most important factors in molecular recognition by a biomolecule. There is a developing appreciation that 3D fragments could offer opportunities that are not provided by 2D fragments.

MCE 3D Diverse Fragment Library consists of 5,400 non-flat fragment-like molecules (average Fsp3 value 0.58). More than 4,700 fragment compounds contain at least one chiral center in the structure. The key concepts that underlie the library design were 3D shape, structural diversity, reactive functionality and fragment-like. This 3D Diverse Fragment Library brings higher fragment hit optimization and increases the likelihood to find innovative hits in FBDD.

A diverse compound library with favorable ADMET properties (Absorption, Distribution, Metabolism, Excretion, and Toxicity) is crucial in drug discovery. Early evaluation of ADMET properties allows for the exclusion of molecules with unfavorable profiles at the initial stages, thereby reducing the risk of late-stage development failures, lowering R&D costs, and accelerating optimization of lead compounds. Based on predictions from ADMET-related AI algorithms, the compounds in this library are predicted to exhibit favorable oral bioavailability (F > 30%), reasonable plasma protein binding (PPB < 98%), minimized CYP3A4 inhibition potential (inhibition probability < 50%, CYP3A4 is the most critical drug-metabolizing enzyme in the cytochrome P450 family) , low toxicity profiles, with 140 potentially toxic substructures pre-identified and excluded via substructure searching to eliminate compounds containing hazardous fragments. The diversity library enables broad applicability in high-throughput screening (HTS) and high-content screening (HCS).

The anti-cancer drug library meticulously collects all drugs approved by FDA and other major national drug regulatory authorities for cancer treatment. These drugs cover a variety of cancer types, including but not limited to lung cancer, breast cancer, colorectal cancer, leukemia, and other common cancers. The library includes a wide range of drugs, from classic chemotherapeutic agents to cutting-edge targeted therapies and immunotherapies. It contains various types of drug compounds with different mechanisms of action. There are cytotoxic drugs that directly kill cancer cells, as well as drugs that work by modulating the tumor microenvironment, inhibiting tumor angiogenesis, and activating the immune system. This diversity provides researchers with a broad range of perspectives and options for intervention strategies.

This library can be used for basic research on cancer treatment, exploring new targets and new mechanisms of drug action; Conducting drug reuse research to look for potential therapeutic effects of existing drugs on other cancer types or diseases; Or conducting research into combination drugs to optimize cancer treatment.

MCE has collected 279 small-molecule compounds with cancer indications, which are good tools for drug repurposing.

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 1,458 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.

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.

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 271 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.

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 5,810 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.

Targeted Protein Degradation (TPD) is a novel and promising approach to drug development. It shows great potential for targeting proteins traditionally considered "undruggable" due to the lack of enzymatic function and absence of binding sites by tagging them for degradation or recruiting natural degradation mechanisms.

Molecular glues are a type of small-molecule degraders that primarily induce novel interactions between E3 ubiquitin ligases and target proteins, forming ternary complexes that lead to protein ubiquitination and subsequent proteasomal degradation. Compared with PROTACs, molecular glues generally have lower molecular weights, higher cell permeability, and better drug-like properties. Additionally, the design of molecular glues is relatively simple, without the requirements for complex linkers and ligand optimization. As a result, molecular glues have gradually emerged as a promising therapeutic approach for various diseases.

Multiple types of molecular glues have been reported previously. Analysis of co-crystal complex structures reveals that CRBN-related molecular glues are more versatile. Therefore, MCE researchers select active molecules related to these targets as probes for artificial intelligence (AI) screening.Subsequently, molecular docking technology was used to verify whether the screened molecules retained the key pharmacophore features. Ultimately, we obtained 320 molecular glue analogs, and these compounds serve as powerful tools for the research of molecular glues.

MCE Magnetic Stand is optimized for efficient magnetic separation of all types of MCE Magnetic Beads with sample volumes ranging from 10 μL to 15 mL.

MCE Seamless DNA Assembly Plus Kit contains an optimized mix of recombinase, reaction buffer, and additional cofactors that significantly improve the cloning efficiency and tolerance to impurities. This product can complete multiple DNA fragments recombination and takes only 5 minutes for single fragment, and the positive rate is more than 95%.

MCE 2-Color Tracking SYBR qPCR Master Mix (Universal) is a 2× concentration premixed reagent utilizing a special performance-enhanced Taq DNA polymerase protected via a hot-start activation technique, and optimized qPCR buffer system to perform SYBR Green I based quantitative PCR (qPCR).

MCE Exosome-Specific Culture Medium (Serum-Free, Phenol Red-Free) is specifically formulated for optimized exosome collection.

MCE Exosome-Specific 293 Cell Medium (Serum-Free) is specifically optimized for exosome production from HEK293 cells.

MCE Exosome-Specific Mesenchymal Stem Cell Medium (Serum-Free, Phenol Red-Free) is specifically optimized for the production and preparation of exosomes from mesenchymal stem cells (MSCs).

The most cited neuronal cell culture supplement, B-27 Supplement is an optimized serum-free supplement used to support the low- or high-density growth and short- or long-term viability of embryonic.