141 results about "Druggability" patented technology

A drug screening method includes the steps: A, screening PPARs (peroxisome proliferator-activated receptors) and building a PPAR action model; B, building a compound database; C, evaluating druggability, LogP, LogS, mutagenicity, tumorigenicity, irritation, reproductive toxicity and water solubility of compounds in the database, and building two-dimensional and three-dimensional compound databases; D, performing structural modification on compounds in the two-dimensional and three-dimensional compound databases; E, performing docking computation on novel molecular structural compounds, and screening; F, verifying the compounds by the aid of a molecular dynamics method, and selecting and determining molecules; and G, obtaining ADMET (absorption, distribution, metabolism, excretion and toxicity) properties of the verified compounds obtained by computation so as to obtain target compounds finally. By the scheme, structures of the compounds are further optimized while structure-function relationship of the compounds is researched, and novel leading compounds with medicinal value are sought.

The invention discloses a preparation method of a fusion protein Trx-TAT-hMsrA and application thereof to an aspect of nerve cell protection. The fusion protein Trx-TAT-hMsrA comprises a TAT protein transduction structure domain, thioredoxin Trx and anthropogenic methionine sulfoxide reductase hMsrA. The fusion protein of the invention has various biological effects for reducing the oxidization of functional protein methionine residues, treating oxidative stress injury, relieving the relevant nerve cell pathological change of parkinsonism, preventing and treating calcium ion overloading and the like, simultaneously has good capability for entering nerve cells through the epicyte, and belongs to novel biotechnological medicine candidates with good druggability.

The invention discloses a glutaminyl cyclase inhibitor. The structure of the glutaminyl cyclase inhibitor is shown in the following formula ( as shown in the description). The glutaminyl cyclase inhibitor (QC inhibitor) provided by the invention is designed according to the crystal structure of an active center of target pheron. The glutaminyl cyclase inhibitor shows favorable selectivity and specifity, and has higher druggability. The glutaminyl cyclase inhibitor is rich in parent structures, good in water solubility, good in transmembrane properties and high in activity.

The invention provides a compound shown in Formula I, an isomer, pharmaceutically-acceptable salt or solvate thereof, a preparation method thereof and application thereof in preparation of drugs for preventing and / or treating diseases caused by a Coxsackie virus. According to the invention, the compound keeps the activity of inhibiting the Coxsackie virus group B; and meanwhile, the pharmacokinetic parameters and safety of the compound drug are improved, thus indicating that the compound provided by the invention has favorable druggability and application prospects. The Formula I is shown in the specification.

The invention provides a dihydroxybenzoylhydrazone neuraminidase inhibitor and preparation and application thereof. The neuraminidase inhibitor is characterized by adopting a structural formula as shown in the description. The neuraminidase inhibitor has excellent anti-H1N1 influenza virus activity, adopts a structure completely different from that of previous neuraminidase, has a good effect of inhibiting A / WSN / 33H1N1 virus strain, is less in toxicity and has high druggability.

The invention relates to the field of medical preparation and polymer materials, and particularly discloses a nanometer preparation of an anticancer natural product (gambogic acid). The nano preparation comprises methoxy polyethylene glycol-polycaprolactone polymer (mPEG-PCL) and gambogic acid, and is formed by encapsulating gambogic acid by methoxy polyethylene glycol-polycaprolactone in a micelle form, wherein the mass ratio of gambogic acid to methoxy polyethylene glycol-polycaprolactone is 1:(5-300). Experimental studies show that when the specific biocompatible material (mPEG-PCL) encapsulates gambogic acid, and the preferred definition of the relationship of dosage of the two is combined, the dispersion of gambogic acid in water can be effectively improved, and the bioavailability and the druggability of the nanometer preparation are enhanced; the anti-tumor effect of gambogic acid is significantly enhanced through passive targeting effect, toxic and side effects are reduced, andtreatment costs are reduced.

The invention belongs to the technical field of medicine, and particularly relates to a paclitaxel palmitate liposome and a preparation method thereof. Paclitaxel palmitate is obtained through esterification of palmitic acid and 2'-bit hydroxyl of the paclitaxel and belongs to a paclitaxel prodrug. The prodrug overcomes the defect of poor lipid solubility of the paclitaxel, and accordingly, the problem of poor druggability of paclitaxel nano-preparations is solved substantially. Aiming at the special physicochemical property of the paclitaxel palmitate, matching between formula composition and preparation technology is researched, the paclitaxel palmitate liposome, which does not contain polyoxyethylated castor oil and is safe, stable in quality and simple to prepare, is developed in a real sense, and the solid foundation is laid for further research and application of the paclitaxel in the anti-tumor field.

The invention relates to an establishing method and application of a dilated cardiomyopathy and zebrafish disease model. A disease model simulating human congenital dilated cardiomyopathy (CDCM) is firstly established; and the disease model can be used as a drug screening model to be applied to screening of drugs capable of relieving symptoms of heart failure caused by CDCM. The method provided by the invention is an economic and rapid high-content screening method; and the obtained compound has relatively high specificity and druggability.

The invention relates to an experiment animal model, and discloses a constructing method and application of an ulcerative colitis (UC) animal model. According to the ulcerative colitis animal model, Canis lupus familiaris is used as a model animal, acetic acid is adopted to cause ulcerative colitis of Canis lupus familiaris, and basically, the experiment result can be directly applied and popularized to the human body. The modeling way is easy to operate, the model is stable, easy to repeat and low in cost, and the animal model selection with more druggability evaluations and curative effect evaluations is provided for development and research of drugs for treating UC.

The invention provides expression and purification methods of a fusion protein containing a recombinant human fibroblast growth factor 21 (hFGF21). In an expression process, the fusion protein is the fusion protein of GST protein and recombinant human fibroblast growth factor 21, is transferred into BL21 after being constructed into a plasmid with a GST tag, is subjected to IPTG induced expression, is greatly expressed in an inclusion body manner and is purified through ion-exchange column chromatography and a GST affinity column, and therefore a large quantity of high-purity proteins are obtained. The expression and purification methods have the beneficial effects that by expressing hFGF21 proteins by virtue of a GST system and optimizing induction conditions, the expression quantity of the proteins is substantially increased; by virtue of purification through the ion-exchange column chromatography and secondary purification through the GST affinity column, the loss of the proteins can be reduced as much as possible, and the purity of the proteins can be effectively improved; and the methods have important practical significance to the development of druggability of the hFGF21 proteins.

The invention discloses a biphenyl furocoumarin compound and a preparation method and an application thereof; the provided biphenyl furocoumarin compound is a new compound with vasodilating activity, which is obtained by modifying and optimizing the structure based on a natural product imperatorin, reserving the pharmacological activity, improving the physicochemical property and enhancing the druggability. The preparation method of the biphenyl furocoumarin compound provided by the invention has the advantages of easily-obtained material source, mild reaction conditions, simple operation in reaction process, and cheap and easily-obtained reagents. The prepared biphenyl furocoumarin compound is a ramification of the imperatorin and has the effect similar to the imperatorin; an in vitro vascular ring tension research shows that the biphenyl furocoumarin compound has a relaxant effect on the mesenteric microvessels of rats, so that the biphenyl furocoumarin compound can be applied to preparing antihypertensive drugs.

The invention discloses an automatic medicine design method and system, computing equipment and a computer readable storage medium. The method comprises the following steps of decomposing a target lead compound into fragments with synthesizable modules, and sequentially inputting the fragments into a trained drug design machine learning model for sampling, and reassembling the new fragment outputby the drug design machine learning model to obtain a new lead compound. According to the automatic drug design provided by the invention, the performance in the aspects of molecule generation effectiveness and uniqueness is greatly improved, and molecules with high novelty, strong synthesizability and strong druggability can be generated; molecules can be easily generated in a high molecular weight region; the method can be repeatedly used for different target point lead compound generation scenes only by using a specific data set to train once; the local structure of the immobilized compoundcan be easily realized, and the rest parts are optimized.

The invention relates to substituted benzylidene tetralone derivatives and a preparation method and application. The chemical structural formula of the substituted benzylidene tetralone derivatives is shown in the formula (1) in the specification, and in the formula (1), X represents CHOH or C=O, and R represents any one of H, OH, F, Cl, CN, CONH2, NO2, CH3, OCH3 and NH2. In the synthetic route, any substitution group can be introduced into two benzene rings, thus eliminating the limit on organic synthesis for finding out compounds with better activity. After water-soluble groups such as amino and the like are introduced, the water solubility can be greatly improved compared with a pilot compound CA-4, and the research of druggability is facilitated. In addition, after amino, hydroxyl and the like are introduced, not only can the bioactivity be improved, but also a prodrug can be prepared on the basis of the group, and the in-vivo activity study can be favorably conducted. The derivatives have the effects of treating ovarian cancer, colon cancer, thyroid cancer and leukemia.

The invention discloses an anhydroicaritin crystal form A and an anhydroicaritin crystal form B and a preparation method thereof and belongs to the technical field of pharmaceutical chemistry. The preparation method of the anhydroicaritin crystal form A and the anhydroicaritin crystal form B is simple in process and high in conversion rate. The prepared crystal form A and crystal form B are single in crystal form and high in purity and has a significantly improved solubility curve when compared with amorphous powder, so that the stability of bioavailability is improved, and the druggability of the anhydroicaritin is facilitated. The structural formula of the anhydroicaritin is shown in the description.

The present invention pertains to the field of pharmaceutical chemicals, and relates to a rapamycin derivative of Formula I, and a preparation method, pharmaceutical composition and use thereof. The compounds of the present invention overcome the defects of rapamycin in terms of water solubility and metabolic properties, and some of the compounds have an in vitro anti-tumor activity superior to rapamycin, have less toxicity to normal cells than rapamycin, and have very good druggability.

The invention provides a nucleic acid molecule. The nucleic acid molecule comprises an immune globulin gene or a fragment of the immune globulin gene. The nucleic acid molecule is characterized by comprising an IgM gene (IgHCmu) and an IgM transduction element (switch region, Smu), and the Smu and the IgHCmu are host animal sequences. The humanoral antibody is directly acquired, the artificial modification in the later period is reduced, and the druggability of the antibody is improved. The development and the maturation of the transgenic B-cells and the number of the B-cells are completely consistent with those of the normal mouse, thereby being favorable for the differentiation of the B-cells; the specificity and the diversity of the produced antibody are improved; and the efficiency ofscreening the therapeutic antibody is improved.

The invention discloses a traditional Chinese medicine composition for treating diseases caused by human papilloma virus and a preparation method and applications thereof. The traditional Chinese medicine composition comprises following components in parts by weight: 15 to 60 parts of smilax glabra, 7.5 to 30 parts of sophora flavescens, 10 to 40 parts of oldenlandia diffusa, 10 to 40 parts of dandelion, 6 to 24 parts of dysosma versipellis, 7.5 to 30 parts of nidus vespae, 10 to 40 parts of phellodendron, 2.5 to 10 parts of brucea javanica, 7.5 to 30 parts of fructus cnidii, 3 to 12 parts oflicorice root, 7.5 to 30 parts of honeysuckle flower, 7.5 to 30 parts of folium isatidis, 5 to 20 parts of radix semiaquilegiae, and 1000 to 2000 parts of ethanol (75%). The provided traditional Chinese medicine composition has good druggability and definite curative effect and is very safe.

The invention relates to the pharmacological effect of phenylethanoid glycoside as an active ingredient in herba cistanche as a traditional Chinese medicine for anti-insomnia and application thereof,and in particular to the preparation of phenylethanoid glycoside and application thereof in drugs for treating insomnia and health-care food. A pharmacological experiment indicates that phenylethanoidglycoside has a strong effect in improving the sleep function. Phenylethanoid glycoside in the herba cistanche has good activity in improving the sleep function, side effects are small, the price islow, the druggability is good, and phenylethanoid glycoside can be used alone or in combination with other drugs for preparing drugs for improving the sleep function. Phenylethanoid glycoside and pharmaceutically acceptable or food-acceptable carriers or excipients can be prepared into dosage forms of granules, capsules, tablets and the like.

The invention relates to an antibody drug conjugate, and an intermediate, a preparation method and application of the antibody drug conjugate. Specifically, the invention discloses the antibody drug conjugate, and the structure of the antibody drug conjugate is shown as Formula I. The antibody drug conjugate has a very strong targeting property, achieves a very good inhibition effect on various tumor cells expressing Claudin 18.2, CD30, Trop2, Her2 and the like, and also has very good druggability and high safety. The invention also discloses an intermediate of the antibody drug conjugate. Theintermediate can be coupled with various antibodies.

The invention relates to the field of biological medicine, in particular to a series of derivatives of a novel CDK9 inhibitor with a benzofuran structure and an application of the novel CDK9 inhibitor. A series of compounds are synthesized by modifying a parent nucleus of wogonin since wogonin has the disadvantages of low antitumor activity and poor druggability; particularly, an N-ring containingsubstituent is introduced into a 3' site or a 4' site; the compounds are brand-new and are not reported in literatures; at the same time, the inventor carries out a series of bioactivity evaluation on the synthesized compounds; and in particular, the most compounds have good selectivity for CDK9 and better inhibition activity for cancer cells.

An o-aminoheteroaryl alkynyl-containing compound has a structure represented by formula (I), and the compound of formula (I) has advantages of a high FGFR and RET double target inhibitory activity and a relatively low KDR activity, and the compound of formula (I) exhibits a strong inhibitory activity in a human lung cancer cell line NCI-H1581 and a gastric cancer cell line SNU16 as well as an RET-dependent sensitive cell line BaF3-CCDC6-Ret and a mutant thereof. Pharmacokinetic data shows that the o-aminoheteroaryl alkynyl-containing compound has druggability, and exhibits significant relevant inhibition of the growth of related tumors in a long-term animal model of drug efficacy and results in favorable animal condition at effective doses.

The invention provides a macrolide derivative of a novel structure. Experiments show that the macrolide derivative has a good promoting effect on alimentary motility and is capable of enhancing intestine peristalsis, increasing defecation quantity and accelerating passing of intestinal content; on such basis, it is further discovered that the macrolide derivative is low in antibiotic activity and small in side effect and can be taken as a gastrointestinal motility promoting drug. Particularly, a compound III-3 screened with the optimal efficacy is subjected to further efficacy evaluation as well as acute toxicity and cardiotoxicity evaluation by domestic rabbits, beagles and marmosets. Experiments show that the compound III-3 is safe and capable of effectively promoting gastrointestinal motility, thereby being excellent in druggability.

The invention discloses a preparation method of an antimicrobial compound Myrtucommulone J, an anticancer compound Myrtucommuacetalone and analogues of Myrtucommulone J and Myrtucommuacetalone. The method comprises the following steps: target products are prepared from unsaturated ketone compounds and monoacyl phloroglucinol compounds in a nonpolar solvent under the action of a trifluoroacetic acid, acetic acid or p-toluenesulfonic acid catalyst through a reaction. Biomimetic total synthesis is realized for the first time, the structure of Myrtucommulone J is further confirmed, and one efficient, reliable and economical preparation method is provided for abundant obtaining of Myrtucommulone J, Myrtucommuacetalone and the analogues of Myrtucommulone J and Myrtucommuacetalone as well as subsequent structure-function relationship and druggability based development and production.

The invention provides a nucleic acid base compound or a medically acceptable salt thereof. The compound or the medically acceptable salt thereof has the obvious inhibitory HIV protease and / or reversetranscriptase activity; toxicity studies show that the compound has the good druggability, it is indicated that the compound has a good application prospect by serving as an anti-AIDs drug. Accordingto experimental data, the compound has inhibitory activity on HIV-1 protease and HIV-1 reverse transcriptase, and low cytotoxicity exits. The nucleic acid base compound or the medically acceptable salt thereof is expected to become a double-target inhibitor inhibiting the HIV protease and the reverse transcriptase simultaneously.

The invention relates to application of an AMHR2 recombinant protein or fused protein in the preparation of drugs for treating AMH signal axis abnormal activation related diseases, and especially application in the preparation of AMH neutralizers or antagonists. Stability experiments show that the AMHR2 fused protein is long in half-life period, excellent in in-vivo stability and strong in AMH binding force, and has certain druggability. Cell experiments and animal model experiments show that the AMHR2 recombinant protein or the AMHR2 fused protein can effectively antagonize or neutralize AMHin vitro and vivo, can further block an AMH signal axis, and can effectively prevent and treat diseases caused by abnormal activation of the AMH signal axis.

The present invention discloses a nitrogen-containing fused heterocyclic compound, as well as a preparation method, intermediate, composition and application thereof. The nitrogen-containing fused heterocyclic compound of the present invention as represented by formula (I), as well as the pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, metabolite or drug precursor thereof, exhibit a high selectivity and a high inhibitory activity with respect to CDK4 and CDK6 at a molecular level, an excellent inhibitory activity with respect to breast cancer cells at a cellular level, and significant inhibition of tumor cell proliferation associated with cyclin-dependent kinase activity at an animal level. The invention also exhibits a good stability with respect to human or mouse liver microsomes without significant inhibition of metabolic enzymes, good in vivo absorption in mice and rats, a high bioavailability and good druggability.

The invention provides an amide derivative or a pharmaceutically acceptable salt thereof with the structure as shown in formula I. A compound or the pharmaceutically acceptable salt thereof has significant activity in inhibiting HIV protease and reverse transcriptase; toxicity study shows that the compound or the pharmaceutically acceptable salt thereof has better druggability, and the compound has better application prospect in using as anti-Aids drugs. According to experimental data, the compound has inhibiting activity both on HIV-1 protease and HIV-1 reverse transcriptase and has lower cytotoxicity. The compound or the pharmaceutically acceptable salt thereof is expected to be a double-target inhibitor which can inhibit the HIV protease and the reverse transcriptase.

The invention relates to the field of biological medicines, and relates to a conversion method of a euphorbia lathyris diterpene compound. The method comprises the following steps of utilizing a known microorganism to perform microorganism conversion on the euphorbia lathyris phorbol and a derivative thereof, and combining with chemical acylation, so as to prepare a euphorbia lathyris diterpene derivative compound; especially, utilizing a mucor circinelloides (CICC40242) microorganism to perform hydroxylation biological conversion on the euphorbia lathyris phorbol and euphorbia factor L3, and performing chemical acylation on hydroxyls introduced by C8 and C18, so as to obtain three hydroxylated products and six C8 alcohol esterified products. The method has the advantages that the water solubility of the euphorbia factor L3 is improved by the hydroxylation at site, and the druggability is improved; furthermore, the prepared euphorbia lathyris diterpene compound can be used for preparing anti-tumor activity and anti-tumor multidrug resistance type pharmaceutical compositions. The chemical formula is shown in the specification.