109results about How to "Overcome drug resistance" patented technology

The invention is directed to novel prodrug compounds, compositions comprising the prodrug compounds, methods of making the prodrug compounds and methods of using the prodrug compounds. The prodrug compounds comprise a biologically active entity linked to a masking moiety via a linking moiety. The prodrug compounds are selectively activated at or near target cells and display lower toxicity and possibly a longer in vivo or serum half-life than the corresponding naked biologically active entity.

The invention discloses a pyrimidoheterocyclic compound represented as the formula (I), or a pharmaceutically acceptable salt or a stereisomer thereof, or a prodrug molecule thereof. The pyrimidoheterocyclic compound can effectively inhibit growth of various tumor cells and has an inhibiting effect on EGFR protease. The pyrimidoheterocyclic compound can be used for preparing an anti-tumor drug, and can overcome drug resistance caused by medicines in the prior art, such as gefitinib, erlotinib and the like, has a selectivity on wild non-small cell lung cancer and is excellent in pharmacokinetic property.

The present invention discloses a 3-(2-pyrimidine amino) phenyl acrylic amide compound in the structure of formula (I) or a pharmaceutically acceptable salt or a stereisomer or a prodrug molecule. The 3-(2-pyrimidine amino) phenyl acrylic amide compound or the pharmaceutically acceptable salt can effectively inhibit the growth of various tumor cells, and inhibit EGFR (epidermal growth factor receptor), HER (human epidermal receptor2) family other protease, can be used in the preparation of antitumor drugs, and can overcome the drug resistance induced by gefitinib, erlotinib and the like.

The invention discloses a 5,8-dioxo-pyrimido[4,5-e][1,4]diazepine compound of a structural formula (1) or a pharmaceutically acceptable salt or stereoisomer or prodrug molecule thereof. The 5,8-dioxo-pyrimido[4,5-e][1,4]diazepine compound has the effects of effectively inhibiting the growth of various tumor cells and the generation of the EGFR (epidermal growth factor receptor), can be used for preparing anticancer medicaments and can overcome the resistance of the existing medicaments including the gefitinib, the erlotinib and the like.

The invention discloses a pyrazolopyridines alkynylbenzene compound having a structural characteristic shown in a formula (I) or its pharmaceutically acceptable salt or a stereisomer or prodrug molecules, and an application of the compound and its pharmaceutically acceptable salt or the stereisomer in preparation of medicines for treating or preventing tumor. Compared with a clinical used antitumor drug (imatinib), the compound has obvious advantage for resisting the activity of a plurality of tumor-derived type and drug resistance type cells, and the compound has the characteristics of good pharmacokinetics and low toxicity. The definitions of groups in the formula are disclosed in the specification.

The instant application relates to deazapurines, thienopyrimidines and furopyrimidines with zinc-binding moiety based derivatives and their use in the treatment of phosphoinositide 3-kinase related diseases and disorders such as cancer. The instant application further relates to the treatment of histone deacetylase related disorders and diseases related to both histone deacetylase and phosphoinositide 3-kinase.

The invention discloses a bio-friendly antibacterial coating capable of effectively fixing a cationic antibacterial agent and resisting a bacterial biofilm. The coating can be formed on the surface ofa to-be-modified substrate by placing the to-be-modified substrate in impregnation liquid, and the impregnation liquid is formed by mixing protein, the cationic antibacterial agent and a reducing agent; negative charges, which are presented in an environment with an isoelectric point larger than that of natural proteins such as serum albumin, fibrinogen, alpha-lactalbumin and the like by the natural proteins, can be mutually neutralized with positive charges of the cationic antibacterial agent, thereby obtaining the coating with a surface close to electric neutrality, protein and bacterial debris adsorption can be effectively avoided, the long-term efficient antibacterial and anti-biofilm effects are maintained, and meanwhile, the defect of poor biocompatibility of the bactericidal surface of a traditional cationic antibacterial agent is overcome. The coating disclosed by the invention is simple and convenient in preparation method, biologically safe and universally applicable to thesurfaces of various medical devices, the bactericidal effect of the coating is achieved without depending on antibiotics, and bacterial drug resistance caused by improper use of antibiotics can be effectively avoided.

The invention provides 7-(substituted amino)-3, 4-dihydro-pyrimidine [4, 5-d] pyrimidone-(1H)-ketone compounds represented as general formula (I) or (II) and application thereof in preparing medicines for treating tumors. According to research, the compounds can restrain proliferation of various tumor cells, can be used for targeted restrain of epidermal growth factor receptor (EGFR) kinase, and particularly can effectively restrain single-point mutation or multipoint mutation cancer cells of an EGFR (T790M) mutant strain. Accordingly, the 7-(substituted amino)-3, 4-dihydro-pyrimidine [4, 5-d] pyrimidone-(1H)-ketone compounds can serve as EGFR inhibitors to be used for anti-cancer medicines and have high application values.

Prodrugs based on gemcitabine structure shown in formula (I) as well as their synthetic method and application are disclosed in the present invention, wherein the definitions for the groups of a, b, c, d, E, Z and V are described in the specification. By modifying the N4 group, the solubility, the bioavailability and the organ specificity of the prodrugs are improved. Therefore, the fast metabolism problem is overcome for the produced prodrugs compounds. Intestinal toxicity induced by gemcitabine is decreased. Thereby, the prodrugs can be delivered by oral administration in clinics and further improve their anti-tumor, anti-cancer, anti-infection and diffusion preventing capability, and can also specifically act on liver or colon. The synthetic method is simple and adapted to industrial production.

The invention discloses a 7-oxopyridinopyrimidine compound with a structure shown by formula (I) and a pharmaceutically acceptable salt or a stereoisomer or prodrug molecule thereof. The compound or pharmaceutically acceptable salt provided by the invention can effectively suppress the growth of multiple tumor cells and generate an inhibition effect on other proteases of the Her family of EGFR (epidermal growth factor receptor), can be used for preparing anti-tumor drugs and can overcome the drug resistance induced by the existing drugs gefitinib, erlotinib and the like.

The invention provides therapeutically effective compounds for the prevention and treatment of cancer and pharmaceutical compositions containing these compounds as well as methods of using and administering these compounds. The invention also includes methods of activating a prodrug of these therapeutically effective compounds by the administration of a peptide-directed targeting construct that delivers a prodrug-activating enzyme to a target activation site.

The invention relates to a 2-aminopyrimidine compound and application thereof. The structure of the 2-aminopyrimidine compound is shown as I. The compound can effectively inhibit the activity of EGFRprotein kinase resistance mutants (such as EGFRT790M and EGFRT790M / C797S), and can overcome clinical drug resistance of tumor patients such as patients suffering from non-small cell lung cancer induced by an existing third-generation selective EGFRT790M small molecule inhibitors Osimertinib (AZD9291), Olmutinib (HM6171), Rocketinib (CO-1686) and the like.

The invention relates to the technical field of biological medicines, in particular to a kit for quantum dot nucleic acid detection of urinary tract infection-causing pathogens. The kit comprises a detection membrane strip, a fluorescent detection solution and reaction solutions, wherein the detection membrane strip comprises a nylon membrane and a capture probe fixed to the nylon membrane; the fluorescent detection solution comprises quantum dots for marking the capture probe and coupled with streptavidin on the surfaces; the reaction solutions include a reaction solution I, a reaction solution II, a reaction solution III and a reaction solution IV. The kit has the beneficial effects as follows: the high-throughput, high-sensitivity and high-specificity kit for the quantum dot nucleic acid detection of the urinary tract infection-causing pathogens is provided; the kit has fewer steps and obviously shorter detection time than the existing colorimetric gene chip, has lower equipment cost than an organic fluorescent gene chip, and is conducive to clinical popularization.

The invention relates to an antitumor polypeptide for targeted inhibition on an ERK signal channel and application of the antitumor polypeptide. According to the antitumor polypeptide, a micro-molecule polypeptide for targeted inhibition on the ERK signal channel is established; a series of biological experiment shows that the micro-molecule polypeptide is capable of effectively inhibiting drug resistance of a PI3K / AKT inhibitor or a paclitaxel medicine in the antitumor treatment process for multiple tumors such as prostate cancer, breast cancer, colon cancer and rectal cancer, and has a remarkable synergic antitumor function; as the ERK signal channel exists in multiple tumors and is one of important signal channels for promoting cell growth and tumor generation and development, the micro-molecule polypeptide can be used for treating the tumors, and preferably the micro-molecule polypeptide is used together with the PI3K / AKT inhibitor or the paclitaxel medicine.

Prodrugs based on gemcitabine structure shown in formula (I) as well as their synthetic method and application are disclosed in the present invention, wherein the definitions for the groups of a, b, c, d, E, Z and V are described in the specification. By modifying the N4 group, the solubility, the bioavailability and the organ specificity of the prodrugs are improved. Therefore, the fast metabolism problem is overcome for the produced prodrugs compounds. Intestinal toxicity induced by gemcitabine is decreased. Thereby, the prodrugs can be delivered by oral administration in clinics and further improve their anti-tumor, anti-cancer, anti-infection and diffusion preventing capability, and can also specifically act on liver or colon. The synthetic method is simple and adapted to industrial production.

The invention discloses a composite plant disinfectant and a preparation method thereof. The composite plant disinfectant comprises the main raw materials including lonicera, Chinese atractylodes, scutellaria, crataegus, dandelion, phellodendron, lithospermum and the like, and the raw materials are crushed, immersed in distilled water, boiled, cooled, subjected to standing, filtered, added with chitosan and separately packed, so as to obtain the composite plant disinfectant. The composite plant disinfectant, disclosed by the invention, combines a variety of traditional Chinese medicine extracts for internal use, has good antibacterial function, can well sterilize golden staphylococci, colibacillus and salmonella, prevents microorganism from generating medicine resistance, does not pollute the environment, and is a disinfectant which is relevant to food sterilization, safe, innoxious, residue-free, high in action speed, stable in property and efficient.

The invention discloses pyrimidotricyclic compounds or pyrimidotetracyclic compounds having a structure represented by the formula (I), (II) or (III), pharmaceutically-acceptable salts, stereoisomers, or prodrug molecules. The compounds can inhibit various tumor cells, and especially, the compounds can selectively act on lung cancer cells of EGFR L858R / T790 and EGFR E745 A750 / T790M. Compared to wild type cancer cells, the IC50 of the compounds is 10 times, 100 times or even 1000 times higher. The compounds are a novel protein kinase inhibitor, which can overcome the drug resistance of EGFR-TKI and has selectivity.

The invention provides a scaffold material. The scaffold material is obtained by cross-linking multi-arm amino polyethylene glycol and multi-aldehyde glucan. Compared with the prior art, according tothe scaffold material provided by the invention, a cross-linked grid is formed through the Schiff base effect of aldehyde groups and amino groups; and when a medicine is carried, the medicine can be packaged in a scaffold, and the aldehyde groups rich in the material can be coupled with the amino-containing medicine. Therefore, the medicine is effectively retained in the cross-linked grid; furthermore, the medicine can be locally and slowly released at the focus part, and the problems of quick in-vivo metabolism and low utilization rate of the medicine are effectively solved. The scaffold material has wide development prospects in the application aspects of maintaining in-vivo drug concentration, reducing administration dosage, improving drug utilization rate, avoiding drug resistance andthe like. The scaffold material is simple and mild in preparation, free of selectivity for supported drug types, wide in application range and good in biocompatibility.

The invention discloses a new function of cyanobacteria. Under irradiation of specific wave length lasers, and through photosynthesis, oxygen is generated, the condition of oxygen deficiency caused bytumors can be improved, and the problem of reverse tolerance of chemicals, such as adriamycin can be effectively solved. The cyanobacteria is subjected to photosynthesis in light to generate oxygen,and under the aerobic condition, hypoxia factors are reduced for tumor cells, so that multidrug resistance genes can be restrained, expression of P-glycoprotein is restrained to restrain exocytosis ofcancer cells on adriamycin, the reverse tolerance of the cancer cells on the reverse tolerance is overcome, and the antitumor treatment effect can be increased.

A drug carrier is provided with a structure of a lipid shell enclosing aqueous micelles. The lipid shell includes lipid and emulsifier, in which the emulsifier encloses the lipid. The components of the aqueous micelles are phospholipids and amphiphilic chitosan, and the aqueous micelles enclose an aqueous solution containing a drug. Furthermore, the method of preparing the drug carrier is also provided. Therefore, with the pharmaceutical advantages of lipid-based nanoparticle included low drug leakage and the ability of to overcome the multiple drug resistance, this new formulation were further incorporated with the chitosan and featured with high payload efficiency. The features could enhance intracellular concentration of anti-cancer drug and oral bioavailability.

Advancements in solid tumor (e.g., renal cell carcinoma) treatments and imaging are described. The advancements are based on nanoformulations that: (i) overcome deliverability issues associated with anti-cancer compounds; (ii) have increased targeted delivery to tumors, and hypoxic cores of tumors due to the presence of targeting ligands; (iii) have increased delivery to the hypoxic cores of tumors due to engineered shapes; (iv) provide synergistic treatment combinations; and / or (v) overcome cancer cell resistance to therapeutic treatments.

The invention provides an encoding gene of a BCR-ABL fusion protein mutant. A nucleotide sequence of the encoding gene is represented as the SEQ ID No.1. The invention also provides an expression carrier including the nucleotide sequence and a construction method thereof, and also provides the BCR-ABL fusion protein mutant. The BCR-ABL fusion protein mutant is designed on the basis of BCR-ABL / c-ABL SH3 structural domain locus mutation. Threonine at the 79th position of the ABL SH3 structure is mutated into tyrosine, wherein an amino acid sequence of the tyrosine is represented as the SEQ ID No.2. A constructed BCR-ABL fusion protein mutant is competitively combined with R1N1 for directly blocking and reducing combination of intracellular R1N1 and BCR-ABL. With combination of IM, sensitivity of cells on the IM is further increased, apoptosis of tumor cells are promoted and meanwhile potential complications caused by direct knockout of an R1N1 gene are overcome.

The invention relates to the technical field of biological medicines, specifically to a kit for detecting quantum dot nucleic acid of a bloodstream infection pathogen. The kit comprises a detecting membrane strip, a fluorescence detecting solution and a reaction solution, wherein the detecting membrane strip comprises a nylon membrane and a capture probe fixed to the nylon membrane; the fluorescence detecting solution comprises quantum dots for marking streptavidin which is coupled on the surface of the capture probe; the reaction solution comprises a reaction solution I, a reaction solution II, a reaction solution III and a reaction solution IV. The kit has the beneficial effects of being high in throughput, flexibility and specificity; the steps are fewer than the steps of the conventional color-developing gene chip; the detection time is obviously shortened; the cost is less than that of an organic fluorescence gene chip device; the kit is beneficial for clinical popularization.

The present invention provides a broad-spectrum malassezia-resistant natural product composition. The broad-spectrum malassezia-resistant natural product composition consists of tropolone, cinnamaldehyde and nisin. In-vitro drug sensitivity experiments prove that the tropolone, cinnamaldehyde and nisin have an obvious inhibition effect on malassezia, besides, the three materials have synergistic or addition effects, so that compounding of the three materials can reduce drug dosage, enhance a sterilization effect and prevent drug resistance. The composition can be made into drugs and daily chemical products which can be used for treating skin diseases caused by malassezia, such as seborrheic dermatitis, dandruff, etc. Compared with synthetic drugs, the natural product composition is strongin micro-organism-inhibiting ability, natural and free of toxicity, stable in property, small in damages to the environment, low in stimulation, obvious in effects, etc., and has wide application prospects.

The invention provides an N2-carbamylaryl-2-aminopyrimidine derivative and a medical application thereof. The N2-carbamylaryl-2-aminopyrimidine derivative provided by the invention comprises an optical isomer of the N2-carbamylaryl-2-aminopyrimidine derivative and pharmaceutically acceptable salt thereof. Pharmacodynamic research shows that the traditional Chinese medicine composition has no toxicor side effect, the compound has an FLT3 inhibitory activity. The proliferation inhibition activity is realized on various leukemia cell strains; a medium inhibition effect is achieved on breast cancer cells; moreover, the polypeptide is effective for multiple mutations of AML, such as internal tandem repeat mutation of a near-membrane structural domain and D835 point mutation of an activated ring in a kinase structural domain, almost has no inhibition effect on c-KIT, can overcome drug resistance brought by clinical point mutation, can reduce toxic and side effects of bone marrow inhibition,and can be applied to preparation of antitumor drugs. The structures of the general formulas Ia and Ib of the N2-carbamylaryl-2-aminopyrimidine derivative are shown in the specification,

The invention discloses a compound used as an estrogen-related receptor regulator and an application of the compound. The compound is a 1-hydrogen-1, 2, 3-triazole compound with a structure as shown in formula (I) as well as pharmaceutical acceptable salt or prodrug molecule. The compound as well as pharmaceutical acceptable salt or prodrug molecule can be used for preparing drugs for adjusting activity of estrogen relevant receptor (ERR), preventing and treating breast cancer (comprising diseases which are free of influence of an anti-estrogen method), prostatic cancer or metabolic diseases. The formula (I) is as shown in the specification.

The invention provides an application of a laetiporus sulphureus extract to preparation of a medicine for resisting hepatitis b virus. The laetiporus sulphureus extract is an extract obtained throughperforming refluxing on a laetiporus sulphureus fruiting body or mycelium with an alcohol solvent, wherein the alcohol solvent comprises ethanol, and the concentration of the ethanol is 95% and above.The laetiporus sulphureus and components thereof can prevent hepatitis b infection, treat hepatitis b infectious hepatitis, prevent liver cancer, treat hepatitis b relevance liver cancer, and preventrecurrence. The laetiporus sulphureus extract has positive effects in the overall process of pathological changes. The laetiporus sulphureus extract has important significance on solving the difficult problem of clinical treatment of hepatitis b infection and particularly solving the difficult problem of a hepatitis b relevance liver cancer technique.

The invention discloses a primer for detecting low-frequency mutation of an epidermal growth factor receptor gene T790M and an application of the primer, and belongs to the field of molecular pathological diagnosis. The primer comprises amplification primers shown by SEQ ID NO:1-2, a sequencing primer shown by SEQ ID NO:3, and an amplification refractory primer shown by SEQ ID NO:4, wherein the last two bases of a 5' terminal of the amplification refractory primer are same as the first two bases of a 3' terminal of an upstream primer of the amplification primers; the 5' terminal of the SEQ ID NO:2 is used for marking a biotin; the 3' terminal of the SEQ ID NO:4 is used for performing phosphorylation treatment; and the above nucleotide sequences are used together in one detection. The primer provided by the invention improves detection sensitivity, can be used for detecting mutation of less than 0.1%, and ensures that results are intuitive, determination is simpler, more accurate and faster, the false negative rate of detection results is greatly reduced, and useless or useful clinical targeted medicine selection for patients is avoided, thereby saving precious treatment time for the patients, and improving the quality of life of the patients.