61 results about "HIV Proteinase" patented technology

The present invention provides a therapeutic compound of formula (I) and their pharmaceutically acceptable salts for the prevention and treatment of lipodystrophy caused because of HIV infection or combination therapy of HIV-1 protease inhibitors (Pis) and / or reverse transcriptase inhibitors (nRTIs) by neutralizing lipohypertrophy, lipoatrophy and metabolic abnormalities in HIV patient.

The invention relates to a combination of treatments, more particularly a combination treatment for HIV-1 infection. The present invention is directed to the use of bryostatin-1 and their natural and synthetic derivatives for AIDS therapy, in particular to the use of bryostatins in combination with other active drugs such as Histone Deacetylases (HDACs) inhibitors and anti-retrovirals, for the treatment of HIV-1 latency. According to the present invention, we provide a combination therapy for the treatment of HIV-1 latency which employs bryostatin-1 (and analogues) and one of the following HDAC inhibitors; valproic acid, butyrate derivatives, hydroxamic acids and benzamides. While HDACi can be used in continuous dosing protocol, bryostatins can be used following a cyclical dosing protocol. Bryostatins can be formulated in pharmaceutical acceptable carriers including nanoparticles, phospholipids nanosomes and / or biodegradable polymer nanospheres. This combination therapy needs to be used in patients treated with antiretroviral therapy (HIV-1 protease inhibitors, HIV-1 reverse transcriptase inhibitors, HIV-1 integrase inhibitors, CCR5 co-receptor inhibitors and fusion inhibitors).

Described are novel protease inhibitors and methods for using said protease inhibitors in the treatment of human immunodeficiency virus (HIV) infection.

A mammalian protein, like the human serum transferrin (HST), is modified with an inserted peptide sequence flanked at both ends by cleavage sites. The peptide insert contains a motif known to induce apoptosis in cells and the cleavage sites are specific for the viral protease of HIV-1. The delivery of such recombinant transferrin into an HIV-1 infected cell results in the release of the peptide which then induces apoptosis. The peptide is inserted into surface exposed loops of the N-terminal lobe of the HST containing the RGD motif flanked by two modified p17 / p24 HIV-1 protease cleavage sites. When delivered to the infected cell the cleavage of the loop inserted sequences by the HIV-1 protease results in the release of the central RGD-containing peptide sequences. Peptides containing the RGD motif (arginine, glycine, aspartic acid) have been shown to induce cell apoptosis even in small concentrations.

Compounds useful for inhibiting HIV protease are disclosed. Methods of making the compounds, and their use as therapeutic agents, for example, in treating wild-type HIV and of multidrug-resistant strains of HIV, also are disclosed.

Inhibitors of HIV-1 protease and compositions containing them are described. Use of the inhibitors and compositions containing them to treat HIV, AIDS, and AIDS-related diseases is described.

The present invention discloses a novel combination therapy for HIV-1 treatment relying on a combination of at least one CCR5 antagonist, at least one HIV-1 protease inhibitor and at least one pharmacokinetic enhancer of said at least one CCR5 antagonist and / or at least one HIV-1 protease inhibitor. The combination is intended for use in oral treatment of a disorder selected from the group consisting of HIV-1 infection, retroviral infections genetically related to HIV and AIDS, in a treatment-naïve patient infected with CCR5 tropic HIV-1 virus.

The invention belongs to the technical field of medicine and relates to a tertiary amine derivative as shown as the general formula I, and pharmaceutically acceptable salt or a prodrug of the tertiary amine derivative. Results of experimental studies show that the tertiary amine derivative has higher capacity of inhibiting the activity of HIV-1 (human immunodeficiency virus-1) protease and is expected to be developed into an effective drug for resisting Aids.

The present invention provides a therapeutic compound of formula (I) and their pharmaceutically acceptable salts for the prevention and treatment of lipodystrophy caused because of HIV infection or combination therapy of HIV-1 protease inhibitors (PIs) and / or reverse transcriptase inhibitors (nRTIs) by neutralizing lipohypertrophy, lipoatrophy and metabolic abnormalities in HIV patient.

A method of treating HIV infection in a human patient wherein the infecting HIV strain has become resistant to atazanavir, the method comprising administration of a therapeutically effective amount of a combination of atazanavir or a pharmaceutically acceptable salt thereof, and at least one other HIV protease inhibitor. A method for enhancing the effectiveness of a second HIV protease inhibitor in treating HIV infection in a human patient whose HIV strain has become resistant to atazanavir or a pharmaceutically acceptable salt thereof, comprising administering to said human patient an amount of atazanavir or a pharmaceutically acceptable salt thereof effective in maintaining the resistant strain, in combination with the second HIV protease inhibitor. The resistance to atazanavir in the human is manifested by the existence of the signature mutation consisting of I50L mutation in the HIV protease.

The invention provides an application of stilbene glucosides in preparing drugs for treating and preventing AIDS. Structural formulas of the stilbene glucosides are show as a general formula (I), wherein R1, R2, R3, R4, R5 or R6 independently represent hydrogen, hydroxyl, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 acyloxy, halogen, nitryl, trifluoromethyl or a cyano group, and pre-conditions are that at least one of R1, R2 and R3 is the hydroxyl, at least one of R4, R5 and R6 is the hydroxyl, and at least one hydroxyl of R1, R2, R3, R4, R5 and R6 is connected with sugar. In the compounds represented by the general formula (I), an inhibitory activity (IC50) for the HIV-1 protease of 2,3,5,4-tetera-hydroxystilbene-2-O-beta-D-glucoside of the stilbene glucosides for reaches 126 [mu]M.

The invention provides application of lignin-class chemical compounds in preparing medicine for healing and preventing acquired immune deficiency syndrome, wherein the lignin-class chemical compounds are 6'-O-methyl honokiol, Randaiol, Magnolignan C and Strebluslignanol. The Strebluslignanol has good human immunodeficiency virus-1 (HIV-1) protease inhibitory activity, and the half maximal inhibitory concentration (IC50) of the Strebluslignanol reaches 35 %mM. The lignin-class chemical compounds are made from cortex magnolia officinal extract.

The present invention provides an oligopeptide compound with an amino acid sequence of Tyr-Leu-Val-Leu-His (SEQ ID NO:1) and HIV-1 protease inhibitory activity. The oligopeptide compound provided by the invention can be produced from chemical synthesis, or recombination, or microorganism (particularly actinomycetes) extraction. The invention also provides an extract obtained from microorganism (particularly actinomycetes) and having HIV-1 protease inhibitory activity and a preparation method thereof. The extract contains the oligopeptide compound provided by the invention. The invention also provides microorganisms (particularly actinomycetes, such as Actinomyces CGMCC 4766) for obtaining the oligopeptide compound or extract provided by the invention. The oligopeptide compound or extract provided by the invention can be used for prevention and treatment of HIV infection related diseases, such as AIDS.

This invention relates to system construction, preparation method and application of a new type of HIV proteolytic enzyme cutting model. This invention discloses a recomposed HIV proteolytic enzyme substrate molecule that carry with evolution immunoglobulin binding molecule, it is the protein which amino acid sequential showed as SEQ ID NO: 1 or has conservatism variation. This invention also discloses the preparation method and application of above protein, and the preparation method and application of its bacteriophage. This HIV proteolytic enzyme cutting model be able to used in judging HIV proteinase activity, judging sensibility of HIV proteolytic enzyme to proteolytic enzyme depressor drug, and screening HIV proteolytic enzyme depressor drug.

The present invention discloses the preparation process of peptide as HIV proteinase inhibitor. The peptide compound and its medicinal acid added salt may be used as HIV proteinase inhibitor. The preparation process of the present invention has mild technological condition, easily obtained material and high yield, and is suitable for industrial 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 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 provides a method for screening an HIV protease inhibitor based on combination of a fluorogenic substrate and crystal soak. The method comprises the steps of measuring inhibitory activity of a series of compounds that are separated and purified from natural products to the HIV-1 protease; and finally separating and purifying the series of compounds into a single component, wherein the single component is a small molecular inhibitor of the natural products. With the above method, the extract of the Berberis nummularia Bge is found to have effective inhibitory activity for the HIV-1 protease; small molecules with relatively strong combination capacity for the HIV-1 protease are found via the crystal soak method; then the inhibitory activity of the small molecules to the HIV-1 protease is determined via enzyme activity assay; and finally a small molecular inhibitor capable of effectively inhibiting the activity of the HIV-1 protease is provided. Besides, a method for screening anti-HIV materials by the combination of the small molecular substance and an HIV protease compound is provided, novel sites that the HIV protease can interact to the inhibitor are provided, and a method for screening the anti-HIV active materials by using the sites is provided.

The invention provides a method for separating and purifying inclusion body-type HIV-1 (human immunodeficiency virus-1) protease from a prokaryotic system. In the method, a low-concentration detergent and ultrasonic disruption are combined to separate impurity protein from target protein, and an Amicon stirring type ultrafiltration device is used in an operation process, so that the purifying time of the inclusion body protein is effectively shortened. Moreover, the protein renaturation in the method is implemented by dialysis renaturation, the dialysis process is mild, and the activity and purity of the renatured protease are relatively high. The protein crystallization growth and enzyme kinetics measurement can be performed through simple ultrafiltration concentration, and the method is applied to the study of crystallography and enzymology.

Compounds of the formula I:whereinR1, R2, X and N are as defined in the specification;E is N, CH;A′ and A″ are terminal groups as defined in the specification.The compounds have utility as HIV-1 protease inhibitors.

The present invention relates to a chiral amine compound. It is prepared through asymmetrical Henry reaction of amino aldehyde, obtained through the conversion of amino acid and amino alcohol, as acceptor with nitro alkane with molecular formula of R6NO2 in the presence of chiral carbamidine as catalyst. The compound may be used to synthesize a HIV proteinase inhibitor with wide application.

HIV protease inhibitors are disclosed which are characterized as having both hydroxyethylamine and N-heterocyclic moieties.

Selected heterocyclecarbonyl amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease. The present invention relates to such retroviral protease inhibitors and, more particularly, relates to selected novel compounds, compositions, and methods for inhibiting retroviral proteases, such as human immunodeficiency virus (HIV) protease, prophylactically preventing retroviral infection or the spread of a retrovirus, and treatment of a retroviral infection.

The invention provides an application of a traditional Chinese medicine Cassia fistula L. fruit in preparing medicines used for treating AIDS, and especially in preparing medicines used for inhibiting HIV-1 protease. A Cassia fistula L. fruit ethyl acetate extract provided by the invention has an HIV-1 protease activity inhibition rate of 83.4%. IC50 of HIV-1 protease inhibition activity of piceatannol separated from Cassia fistula L. fruit is 59mum.

Selected sulfonylalkanoylamino hydroxyethylamine sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease. The present invention relates to such retroviral protease inhibitors and, more particularly, relates to selected novel compounds, composition and method for inhibiting retroviral proteases, such as human immunodeficiency virus (HIV) protease, prophylactically preventing retroviral infection or the spread of a retrovirus, and treatment of a retroviral infection.

The invention provides a purpose of a Chinese medicine lychee seed in preparing of drugs for treating aids, and particularly provides a purpose in preparing of drugs for restraining HIV-1 protease. The IC 50 value of extractives for inhibitory activity of the Chinese medicine lychee seed to the HIV-1 protease is 10.34 microgram per milliliter.

The invention discloses a strain kit for screening and evaluating AIDS (acquired immune deficiency syndrome) therapeutic drugs. The invention provides a kit which comprises 7 recombinant HIVs (human immunodeficiency viruses): HIV-M46I virus strain, HIV-I54V virus strain, HIV-V82A virus strain, HIV-M46I / N88S virus strain, HIV-G48V / I54V virus strain, HIV-M46I / V82T / I84V virus strain and HIV-G48V / I54V / V82A virus strain. Site-directed mutagenesis is utilized to establish a set of HIV-1 proteinase inhibitor drug-resistant mutant strains. The earlier stage test proves that the HIV-1 proteinase inhibitor drug-resistant mutant strains have certain drug resistance to the proteinase inhibitors in the market at present. The new drugs can only have potential marketing value when having favorable antivirus effects for the strains. Therefore, the kit is applicable to preclinical pharmacodynamic evaluation of AIDS therapeutic drugs.

A mammalian protein, like the human serum transferrin (HST), is modified with an inserted peptide sequence flanked at both ends by cleavage sites. The peptide insert contains a motif known to induce apoptosis in cells and the cleavage sites are specific for the viral protease of HIV-1. The delivery of such recombinant transferrin into an HIV-1 infected cell results in the release of the peptide which then induces apoptosis. The peptide is inserted into surface exposed loops of the N-terminal lobe of the HST containing the RGD motif flanked by two modified p17 / p24 HIV-1 protease cleavage sites. When delivered to the infected cell the cleavage of the loop inserted sequences by the HIV-1 protease results in the release of the central RGD-containing peptide sequences. Peptides containing the RGD motif (arginine, glycine, aspartic acid) have been shown to induce cell apoptosis even in small concentrations.