51 results about "Aminopeptidase N" patented technology

The invention relates to novel compounds of formula (I): H2N—CH(R1)—CH2—S—S—CH2—CH(R2)—CONH—R5, wherein R1 is a hydrocarbon chain, phenyl or benzyl radical, methylene radical substituted by a 5 or 6 atom heterocycle; R2 is a phenyl or benzyl radical, a 5 or 6 atom aromatic heterocycle, methylene group substituted by a 5 or 6 atom heterocycle; R5 is a CH(R3)—COOR4 radical, wherein R3 is hydrogen, an OH or OR group, a saturated hydrocarbon group, a phenyl or benzyl radical and OR4 is hydrophile ester, or 5 or 6 membered heterocycle comprising several heteroatoms selected from a group consisting of nitrogen, sulphur and oxygen, with at least two nitrogene atoms, wherein said heterocycle is substitutable by an alkyl C1-C6, phenyl or benzyl radical. The use of the inventive compounds in the form of drugs, a pharmaceutical composition comprising said compounds, a pharmaceutically acceptable excipient, the use in conjunction of at least one type of cannabinoid derivative for potentiating the analgesic and antidepressant effect of the novel compounds of formula (I) and / or morphine or the derivatives thereof are also disclosed.

The invention provides a carbamido peptide aminopeptidase N inhibitor and application thereof. The invention provides the superactive peptide aminopeptidase N inhibitor, thereby being capable of curing the disease that the activity or the express of the aminopeptidase N is abnormal. Specifically, the invention relates to a peptide compound with the structures of general formulas (I), (II) or (III), and further relates to various optical isomers thereof, a pharmaceutically acceptable salt, a solvate and a prodrug. The invention further relates to a drug composite of the peptide compound which comprises the structures of the general formulas (I), (II) or (III) and use therefore for preparing the drug.

The invention provides a cyclic NGR polypeptide, a radionuclide-labeled aminopeptidase targeting molecular probe and application thereof. The molecular probe is obtained by labeling the cyclic NGR polypeptide with radionuclide, or coupling the cyclic NGR polypeptide with a bifunctional chelating group, and then labeling the coupled product with radionuclide. The radionuclide-labeled aminopeptidasetargeting molecular probe can be used for preparing a developing agent for diagnosing aminopeptidase N (CD13) high-expression tumors or preparing a drug for biological targeting treatment of aminopeptidase N (CD13) high-expression tumors. The integrin receptor can be accurately positioned in vivo, the aim of tumor molecular imaging is achieved through nuclear medicine imaging, and the in-vivo targeting property and the retention time thereof can be remarkably improved. And the aminopeptidase N (CD13) tumor can be accurately positioned as a carrier of radioactive therapy nuclide, so that the aim of treating tumors is fulfilled. The structural formula of the cyclic NGR polypeptide is shown in the specification.

The invention provides an intensive antitumor medicament, namely bestatin deanol ester, a preparation method and application thereof. The bestatin deanol ester not only can effectively inhibit ectopic expression of aminopeptidase N activity, but also greatly improve the water solubility of the parent drug bestatin of the bestatin deanol ester, has slow release effect, is more excellent than the parent drug bestatin either from healing effect or preparation, and has wide application. Particularly, the invention mainly relates to the following three aspects: (1) design and synthesis of the bestatin deanol ester; (2) N'N deanol which is a micromolecule fragment, can be connected with other medicaments containing carboxyl, improves the pharmacokinetic property of the medicaments, and improves water solubility; and (3) a method for synthesizing an ester substance to which the invention relates with wide application and mild condition.

The invention relates to a 2-amino-1-(4-nitrobenzophenone)-1-ethanol metalloproteinase inhibitor as well as a preparation and application thereof. The 2-amino-1-(4-nitrobenzophenone)-1-ethanol metalloproteinase inhibitor is a compound with the following general formula (1). Dipeptide-like or kyrine-type compounds of different series can enhance the appetency and metabolization stability of a compound and an enzyme or a receptor and conforms to the basic requirement on inhibitor structures. The invention designs and synthesizes a group of aminopeptidase N inhibitors with totally new structures. A vitro test shows that the inhibitors have no cytotoxin activity, and four compounds which exhibit remarkable vitro inhibitory activity are close to positive control medicine bestatin and can be used as candidate anticancer medicines. The invention also relates to a pharmaceutical composition of a peptide-like compound with a structure indicated by formula (I), and also relates to the pharmacy usage of the pharmaceutical composition.

The invention relates to novel compounds of formula (I): H2N—CH(R1)—CH2—S—S—CH2—CH(R2)—CONH—R5, wherein R1 is a hydrocarbon chain, phenyl or benzyl radical, methylene radical substituted by a 5 or 6 atom heterocycle; R2 is a phenyl or benzyl radical, a 5 or 6 atom aromatic heterocycle, methylene group substituted by a 5 or 6 atom heterocycle; R5 is a CH(R3)—COOR4 radical, wherein R3 is hydrogen, an OH or OR group, a saturated hydrocarbon group, a phenyl or benzyl radical and OR4 is hydrophile ester, or 5 or 6 membered heterocycle comprising several heteroatoms selected from a group consisting of nitrogen, sulphur and oxygen, with at least two nitrogene atoms, wherein said heterocycle is substitutable by an alkyl C1-C6, phenyl or benzyl radical. The use of the inventive compounds in the form of drugs, a pharmaceutical composition comprising said compounds, a pharmaceutically acceptable excipient, the use in conjunction of at least one type of cannabinoid derivative for potentiating the analgesic and antidepressant effect of the novel compounds of formula (I) and / or morphine or the derivatives thereof are also disclosed.

The invention belongs to the technical field of drugs, and particularly relates to aminopeptidase N inhibitor, a preparation method and application to tumor resistance. The technical scheme includes that the aminopeptidase N inhibitor is chemically named as (S)-4-methyl-2-(3-naphthyl-1-ylmethyl-ureido)-valeryl group hydroxylamine. The constitutional formula (I) of the aminopeptidase N inhibitor is shown here. The pharmacodynamic effect of the aminopeptidase N inhibitor is evaluated by in-vitro APN (adiponectin) inhibitory experiments, in-vitro resistance to tumor cell invasion, antiangiogenesis and mouse in-vivo resistance to melanoma manual transfer and antiangiogenesis experiments.

The invention discloses applications of a urine molecule, which can be used for detection of tumor canceration and indicates whether an individual or a person tested has a cancer or not or whether the individual or the person tested has the possibility to have a cancer or not. Through carrying out different molecule screening of tested tumor urine, the level contents of leucine-rich-2-glycoprotein-1 and aminopeptidase N in the tested tumor urine sample can be detected, testified, and analyzed, wherein the different molecule expression of leucine-rich-2-glycoprotein-1 is in a positive correlation with tumor canceration, and the different molecule expression of aminopeptidase N is in a positive correlation with tumor canceration malignancy degree. The two tumor-related molecule markers provide novel and convenient lab detection indicators for screening and diagnosing whether an individual has the possibility to have a cancer or an individual has already had a cancer. Compared to the conventional tumor detection methods, which need to draw blood or carry out tissue puncture, the tumor-related molecule detection method provided by the invention has the advantages of non-invasiveness and convenient sampling, and is especially suitable for large-scale screening of tumor high-risk group and detections in basic medical institutions.

The invention relates to novel compounds of formula (I): H2N-CH(R1)-CH2-S-S- CH2-CH(R2)-CONH-R5, wherein R1 is a hydrocarbon chain, phenyl or benzyl radical, methylene radical substituted by a 5 or 6 atom heterocycle; R2 is a phenyl or benzyl radical, a 5 or 6 atom aromatic heterocycle, methylene group substituted by a 5 or 6 atom heterocycle; R5 is a CH(R3)-COOR4 radical, wherein R3 is hydrogen, an OH or OR group, a saturated hydrocarbon group, a phenyl or benzyl radical and OR4 is hydrophile ester, or 5 or 6 membered heterocycle comprising several heteroatoms selected from a group consisting of nitrogen, sulphur and oxygen, with at least two nitrogene atoms, wherein said heterocycle is substitutable by an alkyl C1-C6, phenyl or benzyl radical.; The use of the inventive compounds in the form of drugs, a pharmaceutical composition comprising said compounds, a pharmaceutically acceptable excipient, the use in conjunction of at least one type of cannabinoid derivative for potentiating the analgesic and antidepressant effect of the novel compounds of formula (I) and / or morphine or the derivatives thereof are also disclosed.

The present invention relates to methods for diagnosis of chronic prostatitis / chronic pain pelvic syndrome (CP / CPPS). We have found specific biomarkers that are present in higher concentrations in patients that have chronic prostatitis / chronic pain pelvic syndrome (CP / CPPS) as compared to subjects that have no symptoms of CP / CPPS. In particular, uromodulin (THP), aminopeptidase N (AMPN), dipeptidylpeptidase IV (CD26), neprilysin (NEP), zinc-α-2-glycoprotein (ZA2G) and alkaline phosphatase (ALP) were found to be present at higher concentrations in CP / CPPS patient urine that is voided after prostatic message. Accordingly, the invention is directed to methods for diagnosis of CP / CPPS by monitoring the levels of at least one of these proteins in post-prostatic massage urine, as well as to diagnostic kits designed for diagnosis of CP / CPPS.

The invention relates to a Vero-pAPN (Porcine Aminopeptidase N) cell line. An adopted construction method is a slow virus mediating method. Compared with a Vero cell line which is constructed by parental Vero cells and an instant transfer mode and is used for expressing pAPN, cells of the cell line disclosed by the invention can stably express APN protein at a higher level and improve the PEDV (porcine epidemic diarrhea virus) breeding titer, and become host cells more suitable for multiplication of PEDV. The cells can be applied to subsequent virus culture, separation and purification, and provide host raw materials for preparation of vaccines.

The invention provides NGR targeted peptide of CD13 (aminopeptidase N) and application thereof. The NGR targeted peptide has the amino acid sequence of CNGRVSTNGRC. The invention also provides a fusion protein NGR-TNF (tumor necrosis factor) alpha. The NGR-TNF alpha is the fusion protein formed by the NGR targeted peptide and a TNF alpha. The targeted peptide NGR of the CD13 is designed and screened by a conventional histochemical staining method; and then the NGR peptide is fused with a human TNF alpha by a gene recombination method to obtain the fusion protein NGR-TNF alpha. Through a greatamount of experimental analysis, people find that by the NGR-TNF alpha, the growth of tumor cell can be inhibited by inhibiting the growth of neovascularization in tumor in a targeted mode and the effect of resisting the tumor is achieved.

The invention discloses a method for preparing for tumour formingblood vessel peculiarity binding polypeptide and the admixture protein of human-5. The tumour formingblood vessel peculiarity binding polypeptid-CNGRCVSGCAGRC can separately combine with the tumour formingblood vessel endothelium cell surface high effect expressed aminopeptidase N (CD13). It establishes tumour formingblood vessel peculiarity binding polypeptide and the admixture protein of human-5 and obtains the high effect express in bacillus coli. It also discloses a method for preparing for human Tum-5. The Tum-5 is formed by the 54-132 bits amino acid near the N end of the Tumstatin, which is the function structure area of the Tumstatin anti-vascularization.

The invention discloses a 1,2,3-triazole aminopeptidase N inhibitor as well as a preparation method and application thereof. A compound of the invention has a structure represented by a formula (I) or(II). The invention also provides a preparation method of a 1,2,3-triazole compound and application in preparation of a medicament for preventing or treating a disease associated with abnormal aminopeptidase activity. The formulas (I) and (II) are shown in the specification.

The invention discloses a pAPN gene site-directed modified pig. The pAPN gene site-directed modified pig is obtained by a plurality of technologies, such as constructing a gene vector of porcine aminopeptidase N (pAPN) by adopting a method in genetic engineering and performing cell transfection. The pAPN gene site-directed modified pig is mainly applied in two aspects: 1, the infection of viral diarrhea and K88 of the pig is thoroughly eliminated from a genetic angle, the disease control cost of pig farming is reduced, the pollution to environment caused by pig farming is reduced, and a method for performing healthy cultivation and reducing the abuse of antibiotics is provided; 2, the gene site-directed modified pig is the trial test before researching the screening and clinic of the pathogenesis and related intervention and treatment of related diseases, such as human cancers.

Materials and methods for identifying novel pesticide agents are disclosed herein. Specifically exemplified is a full length aminopeptidase N isolated from Manduca sexta, insect cells expressing APN, and methods of screening pesticide agents using the same. Also disclosed are methods of identifying novel APN inhibitors.

The invention relates to the technical field of bioengineering, and particularly relates to an expression vector and a Vero cell line expressing pig aminopeptidase N. The cell line is deposited in CGMCC and has an accession number of CGMCC NO.12675. The cell line is liable to be infected by PEDV viruses, and has a function of promoting PEDV replication in host cells. Through PEDV culture utilizing the cell line, viruses having a higher virus copy number and a higher virus titer can be obtained. The cell line can be used for laboratory PEDV virus culture, pathogenesis researching, and the like and can be used for efficient production of PEDV vaccines in the industrialization.

The invention discloses pyrazoline aminopeptidase N inhibitors as well as a preparation method and application thereof. The compounds provided by the invention have structures shown in a general formula (I) or a general formula (II). The invention also provides a preparation method of the pyrazoline compounds, and application of the pyrazoline compounds in preparation of medicines for preventing or treating diseases associated with abnormal aminopeptidase activity. The general formula (I) and the general formula (II) are shown in the description.

The invention discloses an APN inhibitor with a fluorescent property. The structural formula of the APN inhibitor is (I) or (II) shown in the specification, wherein R1 is hydrogen, methyl, ethyl, propyl, butyl, amyl, hexyl, benzyl, 2-amino ethyl, 2, 2'-N, N-dimethyl ethyl or hydroxyl; and R2 is hydrogen, halogen or hydrophilic radicals and R is methyl or ethyl. The inhibitor can be used as the aminopeptidase N inhibitor, and can also be used for detecting the tissue distribution of aminopeptidase N and tumor cells and tissue imaging. The APN inhibitor can be used as an anti-solid tumor drug and can also be used for disease diagnosis of abnormal expression of the aminopeptidase N.

The invention provides a method for determining an inhibition ratio of a compound for aminopeptidase N activity. A K562-CD13 cell strain for expressing human source CD13 is taken as an enzyme source for determining the enzyme-inhibiting activity of the compound. The invention also provides a kit for determining the inhibition ratio of the compound for aminopeptidase N activity. The kit is used fordetermining according to the method. According to the technical scheme, the human source CD13 is taken as the enzyme source for evaluating the activity-inhibiting effect of the compound; the accuracyis higher than that of the detection method adopting pig source CD13 in the prior art; the cost is lower and the result is more accurate.

The invention discloses an aminopeptidase N inhibitor which has a chemical name of 2-((S)-3-(3-((S)-2-amino-3-phenylpropyl)urea)-2,6-dioxopiperidine-1-yl)-N-hydroxyacetamide hydrochloride and is a compound with a structural formula (I) described in the specification. The invention further discloses a preparation of the compound and application of the compound in preparation of antitumor medicines. The aminopeptidase N inhibitor obtained by the invention is matched with an active site of aminopeptidase N in space, thereby showing stronger antitumor activity in evaluation of in vitro and vivo antitumor activity evaluation.

The invention discloses a preparation method of a two-photon ratiometric fluorescent probe compound for detecting aminopeptidase N. The structure of the fluorescent compound is represented by formulaI. The probe compound is designed based on the principle of fluorescence resonance energy transfer, a two-photon naphthalene derivative is selected as an energy donor, a p-methylaminophenol fluorophore is used as an energy acceptor, and alanine is introduced as an aminopeptidase N specific recognition unit. The aminopeptidase N is used to preferentially hydrolyze an N-terminal alanyl group, whichcauses the proportional change in a fluorescence emission signal. The compound has the advantages of high sensitivity, high selectivity, large emission shift, and quickness in detection of the aminopeptidase N, can be successfully applied to two-photon fluorescence imaging in living cells and tissues, and provides a potential tool for clinical detection of kidney injuries.

Mixed inhibitors of aminopeptidase N and of neprilysine are described. Pharmaceutical compositions containing at least one of these compounds, used alone or in combination with morphine and derivatives thereof, endocannabinoids and inhibitors of the metabolism thereof, GABA derivatives such as gabapentin or pregabalin, duloxetine or methadone, can be used as an analgesic, anxiolytic, antidepressant or anti-inflammatory.

The invention discloses an aggregation-induced emission fluorescent probe for detecting aminopeptidase N and a preparation method of the aggregation-induced emission fluorescent probe. The structure of a probe compound is shown as a formula I in the specification. The probe molecule is composed of three main parts: a quinoline-malononitrile-based aggregation-induced emission fluorophore, a self-cleavable linking group and an aminopeptidase N (APN) specific recognition group. When the N-terminal alanyl site of the probe compound is accurately hydrolyzed into amino by APN, the exposed amino is used as an electron donating group, and the electron push-pull effect of a conjugated system is promoted, so that the fluorescence is enhanced. The probe has the advantages that the response speed is high, the sensitivity is high, the Stokes shift is large, the emission wavelength is long, when the concentration of a solution is higher, the fluorescence emission is stronger, and the problem of aggregation-induced fluorescence quenching is effectively avoided.

Livestock animals and offspring thereof comprising at least one modified chromosomal sequence in a gene encoding an aminopeptidase N (ANPEP) protein are provided. Animal cells that contain such modified chromosomal sequences are also provided. The animals, offspring, and cells have increased resistance to pathogens, including transmissible gastroenteritis virus (TGEV) and porcine respiratory coronavirus (PRCV). The animals, offspring, and cells can optionally further comprise at least one modified chromosomal sequence in a gene encoding a CD163 protein and / or a SIGLEC1 protein. Methods for producing pathogen-resistant non-human animals or lineages of non-human animals are also provided.

The invention provides NGR targeted peptide of CD13 (aminopeptidase N) and application thereof. The NGR targeted peptide has the amino acid sequence of CNGRVSTNGRC. The invention also provides a fusion protein NGR-TNF (tumor necrosis factor) alpha. The NGR-TNF alpha is the fusion protein formed by the NGR targeted peptide and a TNF alpha. The targeted peptide NGR of the CD13 is designed and screened by a conventional histochemical staining method; and then the NGR peptide is fused with a human TNF alpha by a gene recombination method to obtain the fusion protein NGR-TNF alpha. Through a greatamount of experimental analysis, people find that by the NGR-TNF alpha, the growth of tumor cell can be inhibited by inhibiting the growth of neovascularization in tumor in a targeted mode and the effect of resisting the tumor is achieved.

The present disclosure provides a therapeutic method of treating cancer metastasis by inducing clearance of EVs using a binding agent specific to an EV protein. The method utilizes one or more binding agents specific to EV proteins, where the EV proteins are selected from prostaglandin F2 receptor negative regulator (PTGFRN); basigin (BSG); immunoglobulin superfamily member 2 (IGSF2); immunoglobulin superfamily member 3 (IGSF3); immunoglobulin superfamily member 8 (IGSF8); integrin beta-1 (ITGB1); integrin alpha-4 (ITGA4); 4F2 cell-surface antigen heavy chain (SLC3A2); a class of ATP transporter proteins (ATP1A1, ATP1A2, ATP1A3, ATP1A4, ATP1B3, ATP2B1, ATP2B2, ATP2B3, ATP2B4); CD13 (aminopeptidase N); MME (neprilysin), ENPP1 (ectonucleotide pyrophosphatase / phosphodiesterase family member 1); and NRP1 (neuropilin-1). Further provided herein includes a pharmaceutical composition for the treatment of cancer metastasis.

The invention relates to a 2-amino-1-(4-nitrobenzophenone)-1-ethanol metalloproteinase inhibitor as well as a preparation and application thereof. The 2-amino-1-(4-nitrobenzophenone)-1-ethanol metalloproteinase inhibitor is a compound with the following general formula (1). Dipeptide-like or kyrine-type compounds of different series can enhance the appetency and metabolization stability of a compound and an enzyme or a receptor and conforms to the basic requirement on inhibitor structures. The invention designs and synthesizes a group of aminopeptidase N inhibitors with totally new structures. A vitro test shows that the inhibitors have no cytotoxin activity, and four compounds which exhibit remarkable vitro inhibitory activity are close to positive control medicine bestatin and can be used as candidate anticancer medicines. The invention also relates to a pharmaceutical composition of a peptide-like compound with a structure indicated by formula (I), and also relates to the pharmacy usage of the pharmaceutical composition.