12 results about "Small Molecule Libraries" patented technology

A dual screen technique using DEL and 2DCS screens with libraries of synthesized small molecules and synthesized RNA structures (4,096 targets) delivers bona fide ligand-RNA 3D fold target pairs. One of the newly discovered ligands bound a 5′GAG / 3′CCC internal loop that is present in pri-miR-27a, the oncogenic precursor of microRNA-27a. The DEL-derived pri-miR-27a ligand is cell-active, potently and selectively inhibits pri-miR-27a processing to reprogram gene expression and halt an otherwise invasive phenotype in triple-negative breast cancer cells.

The invention relates to the field of biological medicine and ophthalmic diseases, in particular to a target protein inhibitor for preventing and treating proliferative diabetic retinopathy and a screening method and application of the target protein inhibitor. The screening method comprises the following steps: 1) obtaining a three-dimensional crystal structure of CTSH; 2) constructing a binding pocket at an active site; 3) performing molecular docking and scoring on the small molecule library, and screening candidate compounds with binding energy lower than a preset threshold value; and 4) performing molecular dynamics simulation on the candidate compound and the CTSH compound, and selecting a compound with a stable structure and low binding free energy as an inhibitor. The inhibitor obtained by screening comprises eriodictyin, polygala tenuifolia sucrose ester B or an AP-III-a4 inhibitor. Genetic causal inference proves that CTSH has a causal driving effect on PDR, inflammation and pathological angiogenesis can be remarkably inhibited by regulating CTSH expression under a high glucose condition, and effective inhibitor components are finally screened.

The present invention provides a GPU-based rapid molecular docking method, the purpose of which is to further improve the docking accuracy and speed of the QuickVina2-GPU method. In improving the docking accuracy, the Gypsum-DL method is used to optimize the input small molecule structure; the cross-docking method is used to select the optimal receptor structure; and the Coach-D method is used to optimize the docking pocket of the receptor. In improving the docking speed, the global grid cache is used to accelerate the intermolecular energy calculation of QuickVina2-GPU. In the preparation of the small molecule library, the present invention makes up for the shortcomings of Openbabel in handling small molecule charges, selects receptors with good docking accuracy and can effectively restore the true conformation, reduces the number of data transmissions between the CPU and the GPU, greatly improves the speed of molecular docking, and reduces communication overhead. The present invention can further meet the infinite pursuit of docking speed and accuracy under large-scale drug virtual screening.

The invention discloses a chromone derivative containing a cyclamine structure as well as a preparation method and application of the chromone derivative. The structures of the compounds are confirmed by structural characterization of 1H NMR (nuclear magnetic resonance), 13C NMR (nuclear magnetic resonance), 19F NMR (nuclear magnetic resonance), HRMS (high resolution mass spectrometry) and other analysis and test methods, and all the compounds are new compounds. The synthesis method of the compound has the advantages of no transition metal catalysis, room temperature, short time, easily available reaction raw materials, simple reaction system, wide substrate application range, high yield and the like, and enriches chromone small molecule libraries. The cyclic amine chromone derivative prepared by the invention has certain inhibitory activity on mouse skin melanoma B16-F10 cells, colon cancer HCT-116 cells and cervical cancer Hela cells, and can be used for further development and application of anti-cancer drugs.

The invention relates to the technical field of biology, in particular to application of a glyoxal-based compound in preparation of a probe. According to the invention, the glyoxal-based arginine specific probe is developed, and the reaction activity of arginine in proteome is globally analyzed by utilizing a proteomics analysis method; a fragmented electrophilic small molecule library with a glyoxal structure is constructed, and a new inhibitor is found for protein which cannot be prepared into a medicine through competitive proteomics; and finally, in combination with protein structure calculation and proteome analysis, key ligand arginine for mediating interaction between proteins is found, and the process is disturbed by using inhibitor molecules.

Organic compounds for target identification, drug discovery, chemical library production, high-throughput screening, fluorophore conjugation, chemiluminescent compound conjugation, creation of proximity induced modulators (e.g., protein degraders) / chimeric molecules, or a combination thereof are described. The compounds can contain small molecule moieties for identification of their potential targets; an isocyanate, photoactivatable groups; chemical moieties for enrichment and detection of target-small molecule moiety interactions; proximity induced modulator element; fluorophores; chemiluminescent groups; or combinations thereof.

Provided herein are improved methods for training graph neural networks (GNNs) to predict the binding affinity of novel compounds based on data generated from DNA-encoded library (DEL) experiments. These methods include training the GNN to predict affinity for the target directly and then applying the predicted affinity to a model of the DEL experiment process to generate a predicted DEL read count. The predicted DEL read count can then be compared to an experimentally-observed DEL, read count to generate a loss value. The loss value can then be used to update the GNN as part of a GNN training process. The loss value can be augmented with simulated disynthon data generated from the predicted affinity.

The invention discloses application of hydroxycamptothecin or stereoisomers, derivatives and pharmaceutically acceptable salts thereof in preparation of antiviral drugs, and relates to the technical field of antivirus. The invention finds that hydroxycamptothecin screened from 214 traditional Chinese medicine monomer small molecule libraries by screening small molecule compound libraries can significantly inhibit 3-hydroxyl butyrylation modification of IFN signal key protein STAT1. Cell model and mouse model experiments prove that the hydroxycamptothecin can enhance IFN signals to inhibit the replication capacity of viruses in cells. Therefore, the hydroxycamptothecin has a good broad-spectrum antiviral effect, and is expected to have new application clinically. Meanwhile, a new treatment strategy can be provided for virus infection people.

Microorganisms are prolific producers of natural products, a group of molecules that make up the majority of drugs approved by the FDA in the past 35 years. After decades of mining, the low-hanging fruit has been picked and so discovery of drug-like molecules from microorganisms has come to a near-halt. The reason for this lack of productivity is that most biosynthetic pathways that give rise to natural products are not active under typical laboratory growth conditions. These so-called 'cryptic' or 'silent' pathways are a major source of new bioactive molecules and methods that reliably activate them could have a profound impact on drug discovery. Disclosed herein is a rapid genetics-free method for eliciting and detecting cryptic metabolites using an imaging mass spectrometry-based approach. An organism of choice is challenged with elicitors from a small molecule library. The molecules elicited are then imaged by mass spec, which allows for rapid identification of cryptic metabolites. These are then isolated and characterized. Employing the disclosed approach activated production of cryptic glycopeptides from an actinomycete bacterium. The molecules that result, the keratinimicins and keratinicyclins, are metabolites with important structural features. At least two of these, keratinimicins B and C, are highly bioactive against several pathogenic strains. This approach will allow for rapid activation and identification of cryptic metabolites from diverse microorganisms in the future.

The application discloses a candidate drug molecule screening method and device, and relates to the technical field of bioengineering, and comprises the following steps: obtaining a target target point donor sequence and a splicing regulation database; the splicing regulation database is obtained by variable splicing analysis of each small molecule in a preset splicing regulation small molecule library based on preset processing conditions; a position probability model is constructed based on the statistical probability distribution of base combinations of each splicing donor sequence in the splicing regulation database at different positions; the similarity between the target target point donor sequence and each splicing donor sequence in the splicing regulation database is calculated based on the position probability model; a plurality of candidate splicing regulation sequences are screened out from the splicing regulation database based on the similarity, and small molecules corresponding to each candidate splicing regulation sequence and splicing change amounts are obtained; the consistency proportion of each small molecule is calculated based on the splicing change amount, and the candidate drug molecule of the target splicing donor sequence is obtained based on the consistency proportion and a preset proportion threshold.