197 results about "Anti-apoptosis" patented technology

A pro-apoptotic solid dispersion comprises, in essentially non-crystalline form, a Bcl-2 family protein inhibitory compound of Formula I as defined herein, dispersed in a solid matrix that comprises (a) a pharmaceutically acceptable water-soluble polymeric carrier and (b) a pharmaceutically acceptable surfactant. A process for preparing such a solid dispersion comprises dissolving the compound, the polymeric carrier and the surfactant in a suitable solvent, and removing the solvent to provide a solid matrix comprising the polymeric carrier and the surfactant and having the compound dispersed in essentially non-crystalline form therein. The solid dispersion is suitable for oral administration to a subject in need thereof for treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer.

Salts and crystalline forms of 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}-sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide are suitable active pharmaceutical ingredients for pharmaceutical compositions useful in treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer.

An orally deliverable pharmaceutical composition comprises (a) a pharmaceutically acceptable acid addition salt of ABT-263 in solid particulate form, and (b) a plurality of pharmaceutically acceptable excipients including at least a solid diluent and a solid disintegrant; wherein the salt is formed from more than one equivalent of acid per equivalent of ABT-263. The composition is suitable for oral administration to a subject in need thereof for treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer.

The invention belongs to the field of allogenic mesenchymal stem cells, and particularly relates to a preparation method of allogenic mesenchymal stem cells by CRISPR (clustered regularly interspaced short palindromic repeats) technique editing and IGF (insulin-like growth factor) optimization and application of the allogenic mesenchymal stem cells in treating myocardial infarction. The preparation method comprises the following steps: carrying out separation by density gradient centrifugation to obtain allogenic single karyocytes, and carrying out adherent culture to obtain mesenchymal stem cells; designing a mesenchymal stem cell surface antigen B2M-gRNA and an inflammatory factor TNF-alpha-gRNA; establishing recombinant slow virus particles, and transfecting the mesenchymal stem cells; optimizing the mesenchymal stem cells by using IGF-1; and preparing drugs for treating myocardial infarctions by using the modified and optimized mesenchymal stem cells. The CRISPR / Cas9 technique is utilized to remove the antigens capable of causing immunological rejection and the inflammatory factors capable of causing inflammatory reaction on the mesenchymal stem cell surface, and the IGF-1 is utilized to enhance the apoptosis resistance of the mesenchymal stem cells and promote the homing of the mesenchymal stem cells, thereby providing a new technical scheme for preparing drugs for treating cardiovascular diseases in clinic. The prepared allogenic mesenchymal stem cells can not cause immunological rejection after cell transplantation.

Methods and compositions are disclosed for inducing differentiation and apoptosis in cells that overexpress Notch proteins. A cell fate determining function of Notch is specifically disrupted at a time when the cell is undergoing differentiation, which causes the cell to undergo apoptosis. The invention includes therapies for tumors that overexpress a Notch protein (such as Notch-1) by inducing differentiation of the cells in the tumor with a differentiation inducing agent, such as HMBA, in combination with an agent that disrupts the function of the Notch protein. At a time during which differentiation has been promoted, and the cell is susceptible to interference with the anti-apoptosis effect of Notch, the function of the Notch protein is disrupted. Disruption of Notch function can be achieved, for example, by a differentiation inducing agent, such as HMBA, combined with antibodies that specifically bind to Notch and inactivate it, for example a monoclonal antibody that recognizes Notch-1 EGF-like repeats 11 and 12, such as monoclonal antibodies A6, C11 or F3. Disruption of Notch function can also be achieved by the expression of antisense oligonucleotides that specifically interfere with expression of the Notch protein on the cell, alone or in combination with antineoplastic agents.

A liquid pharmaceutical composition comprises an aqueous medium having suspended therein a solid particulate Bc1-2 family protein inhibitory compound such as ABT-263, having a D90 particle size not greater than about 3 μm; wherein the aqueous medium further comprises at least one pharmaceutically acceptable surfactant and at least one pharmaceutically acceptable basifying agent such as sodium bicarbonate in amounts that are effective together to inhibit particle size increase. The composition is suitable for oral or parenteral administration to a subject in need thereof for treatment of a disease characterized by overexpression of one or more anti-apoptotic Bc1-2 family proteins, for example cancer.

The present invention relates to preventing or delaying programmed cell death by expressing one or more anti-apoptotic polypeptides in a cell such that programmed cell death in the cell is prevented or delayed. The present invention also relates to increasing production of a cell-related product by expressing one or more anti-apoptotic polypeptides in a cell such that production of the cell-related product by the cell is increased. Recombinant cells useful for producing cell-related product or cellular therapy are also provided.

A pro-apoptotic solid dispersion comprises, in essentially non-crystalline form, a Bcl-2 family protein inhibitory compound, e.g., ABT-263, dispersed in a solid matrix that comprises (a) a pharmaceutically acceptable water-soluble polymeric carrier and (b) a pharmaceutically acceptable surfactant. A process for preparing such a solid dispersion comprises dissolving the compound, the polymeric carrier and the surfactant in a suitable solvent, and removing the solvent to provide a solid matrix comprising the polymeric carrier and the surfactant and having the compound dispersed in essentially non-crystalline form therein. The solid dispersion is suitable for oral administration to a subject in need thereof for treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer.

The invention relates to small molecules which function as inhibitors of anti-apoptotic Bcl-2 family member proteins (e.g., Bcl-2 and Bcl-xL). The invention also relates to the use of these compounds for inducing apoptotic cell death and sensitizing cells to the induction of apoptotic cell death.

Provided is a method of treating a proliferative disease, condition, or disorder in a subject by administering a combination of an inhibitor of p53 and MDM2 binding and an EGFR inhibitor. Various embodiments of the disclosed methods provide a synergistic anti-proliferative or anti-apoptotic effect compared to administration of one agent alone.

Novel iron chelators exhibiting neuroprotective and good transport properties are useful in iron chelation therapy for treatment of a disease, disorder or condition associated with iron overload and oxidative stress, eg. a neurodegenerative or cerebrovascular disease or disorder, a neoplastic disease, hemochromatosis, thalassemia, a cardiovascular disease, diabetes, a inflammatory disorder, anthracycline cardiotoxicity, a viral infection, a protozoal infection, a yeast infection, retarding ageing, and prevention and / or treatment of skin ageing and skin protection against sunlight and / or UV light. The iron chelator function is provided by a 8-hydroxyquinoline, a hydroxypyridinone or a hydroxamate moiety, the neuroprotective function is imparted to the compound e.g. by a neuroprotective peptide, and a combined antiapoptotic and neuroprotective function by a propargyl group.

ABT-263 free base and crystalline forms thereof are suitable active pharmaceutical ingredients for pharmaceutical compositions useful in treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer.

An orally deliverable pharmaceutical composition comprises a Bcl-2 family protein inhibitory compound, e.g., ABT-263, a heavier-chalcogen antioxidant and a substantially non-aqueous lipid carrier, wherein said compound and said antioxidant are in solution in the carrier. The composition is suitable for oral administration to a subject in need thereof for treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer.

The present invention provides an inhibitor of NF-κB, guggulsterone and its analogs. Guggulsterone suppresses NF-κB activation induced by TNF, phorbol ester, okadaic acid, cigarette smoke, H2O2 and IL-1β, as well as constitutive NF-κB activation expressed in most tumor cells. One mechanism by which guggulsterone inhibits activation of NF-κB is through suppression of IκBα phosphorylation and IκBα degradation. NF-κB-dependent gene transcription is modulated by guggulsterone and its analogs. In particular, induction by TNF, TNFR1, TRADD, TRAF2, NIK and IKK, is modulated by guggulsterone and its analogs. In addition, guggulsterone decreased the expression of genes involved in anti-apoptosis (IAP1, XIAP, Bfl-1 / A1, bcl-2, cFLIP, survivin), proliferation (cyclin D1, c-myc) and metastasis (MMP-9, COX2 and VEGF).

The invention discloses a thiazole bipyrazolone compound as well as applications thereof in preparing a small molecular inhibitor of Bcl-2 family proteins and antitumor drugs, the thiazole bipyrazolone compound has the above structural formula, and the thiazole bipyrazolone compound has the activity for inhibiting the combination of Bcl-xL and natural substrate polypeptide (Bid BH3 polypeptide) in the micromole range, and can serve as the small molecular inhibitor of the Bcl-2 family proteins for inhibiting the anti-apoptosis activity thereof; and the compound shows a certain inhibitory activity to human breast cancer MDA-MB-231 cells and MCF-7 cells, and is expected to be developed into the antitumor drugs of targeted Bcl-2 family proteins.

An orally deliverable pharmaceutical composition comprises a drug-carrier system having a Bcl-2 family protein inhibitory compound, e.g., ABT-263, in solution in a substantially non-aqueous carrier that comprises at least one phospholipid and a pharmaceutically acceptable solubilizing agent. The composition is suitable for oral administration to a subject in need thereof for treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer.

This invention relates to a novel form of protein C or activated protein C. More specifically, the invention is directed to a variant of protein C that is activated at a higher rate than wild-type or other variants and produces an activated protein C with reduced anticoagulant properties while retaining the protective anti-inflammatory and anti-apoptotic properties of wild-type activated protein C. This novel APC variant will be beneficial for treating inflammatory and apoptotic disorders with a reduced risk for bleeding.

The invention belongs to the field of medicine, which relates to the application of Lycoris radiate alkaloid that is taken as tumor anti-apoptosis factor Mcl-1(myeloid cell leukemia-1) inhibitor, by inhibiting the protein expression of the tumor anti-apoptosis factor Mcl-1(myeloid cell leukemia-1), the diseases that are caused by the protein expression exception of Mcl-1, such as autoimmune inflammations, tumors, and the like, can be cured.

Variants (mutants) of recombinant activated protein C (APC) or recombinant protein C (prodrug, capable of being converted to APC) that have substantial reductions in anticoagulant activity but that retain normal levels of anti-apoptotic activity are provided. Two examples of such recombinant APC mutants are KKK191-193AAA-APC and RR229 / 230M-APC. APC variants and prodrugs of the invention have the desirable property of being cytoprotective (anti-apoptotic effects), while having significantly reduced risk of bleeding. The invention also provides a method of using the APC variants or prodrugs of the invention to treat subjects who will benefit from APC's cytoprotective activities that are independent of APC's anticoagulant activity. These subjects include patients at risk of damage to blood vessels or tissue in various organs caused, at least in part, by apoptosis. At risk patients include, for example, those suffering (severe) sepsis, ischemia / reperfusion injury, ischemic stroke, acute myocardial infarction, acute or chronic neurodegenerative diseases, or those undergoing organ transplantation or chemotherapy, among other conditions. Methods of screening for variants of recombinant protein C or APC that are useful in accordance with the invention are also provided.

The present invention relates to naturally occurring and chemically synthesized small molecule antagonists of XIAP family proteins. In particular, the present invention provides embelin and other XIAP inhibitors and methods of using these compounds as antagonists of the anti-apoptotic effects of XIAP family member proteins. The present invention also provides methods for treating diseases and pathologies (e.g., neoplastic diseases).

The invention relates to a skin care product with anti-blue light effect, wherein the skin care product comprises prebiotics, mung bean seed fermentation broth, water-locking magnet, carnosine, doublenanometer coenzyme Q10 and sunflower bud extract. When the skin care product is applied on the skin, and massage is used, the product increases the activity of cells in the skin layer, so as to enhance the filtering ability of skin to blue light, block the generation of infrared infrared blue light free radicals, reduce and prevent the damage of blue light to skin, prevent the loss of skin density caused by exposure to sunlight, promote the generation of skin collagen, maintain skin elasticity, protect skin and reduce photoaging. At the same time, sunflower bud extract can activate peroxidase-activated receptor (PPAR), PPAR has anti-apoptosis effect, can ensure enough living keratinocytes to participate in the reformation and migration of wound epidermis, so it has skin wound healing andanti-inflammatory effect.

The invention encompasses compositions and methods for effectively treating and / or preventing the development and / or progression of osteoarthritis and rheumatoid arthritis and for promoting overall joint health. This is accomplished by totally addressing the key multiple biochemical processes and mechanisms that lead to such disorders. The invention includes compositions comprising a combination of natural agents that safely and effectively suppress, regulate or interfere with the various biochemical processes and mechanisms that increase the risk for or lead to the development and / or progression of OA and RA. The present compositions are holistically formulated to be effective in preventing / arresting loss of and / or damage to the articular cartilage (AC) by suppressing (a) extracellular matrix (ECM) degradation, (b) chondrocyte apoptosis, and (c) inflammation of synovium through modulation of mechanisms that involve transcription factors, growth factors, kinases, antiapoptotic / apoptotic factors and deacetylases. The active agents used herein are natural materials, in particular phytonutrients (or phytochemicals), minerals and / or vitamins.

The invention discloses an application of a piericidin compound Piericidin A in preparation of anti-renal cancer drugs. The Piericidin A having the structure represented by the formula (I) has inhibitory effect with different intensities on three human renal cancer cell strains, especially has the strongest inhibitory activity on human adrenal carcinoma cells ACHN, and has the half inhibition rate IC50 reaching 0.40 [mu]M. Cell apoptosis experiments show that the Piericidin A can obviously induce late apoptosis of the human adrenal carcinoma cells ACHN, and a fact of inhibiting an anti-apoptosis protein Bcl-2 is one of anti-renal cancer action mechanisms. Therefore, the lead compound Piericidin A can be used as a Bcl-2 inhibitor for development of the anti-renal cancer drugs. The invention provides the new lead compound for development of new microbial-source anticancer drugs.

The invention discloses application of a substance capable of reducing expression of a zinc finger protein CTCF to preparation of drugs for treating leukemia. In particular, the substance reducing expression of the zinc finger protein CTCF can be short hairpin RNA (shRNA) forming a stem-loop structure. The name of the shRNA is shRNA-3. One chain sequence of the stem in the stem-loop structure is SEQ ID No.1 and the other chain sequence of the stem in the stem-loop structure is SEQ ID No.2. The invention proves that the zinc finger protein CTCF is an anti-apoptosis factor and has the function of suppressing cell apoptosis in the ALL (acute lymphoblastic leukemia) cells. Apoptosis of tumor cells-leukemia cells can be promoted by interfering with expression of CTCF. The invention provides a new way for leukemia treatment. The zinc finger protein CTCF is expected to become a potential target for anti-leukemia treatment and has very extensive application prospect in the medical field.

The invention discloses a cell strain MSCs for overexpression of an Nrf2 gene as well as a preparation method and application of the cell strain MSCs. The preparation method comprises the following steps: performing PCR amplification on a human-derived Nrf2 gene ORF; performing purification and double enzyme digestion on the PCR product obtained in the step (1), then connecting the PCR product with the framework plasmid pLV-CMV-XbaI-BamHI-GFP to construct an Nrf2 slow virus recombinant vector, and after conversion, selecting clone and determining positive clone; sequencing the positive clone, and after no mutation is determined, performing amplification massively; leading the recombinant vector and an auxiliary plasmid in a 293 FT cell to obtain a virus; using the virus to infect the 3-5 th generation hUC-MSCs cells so as to obtain the cell strain MSCs for overexpression of the Nrf2 gene. According to the invention, the overexpression of Nrf2 in MSCs is stably performed to increase the cell activity, and a higher anti-apoptosis feature is also realized under the anoxic and oxidative stress conditions; Nrf2-MSCs with the treatment level amount is obtained in vitro and can serve as an excellent tool cell for preclinical study of MSCs and can be used for preparing a medicine for enhancing preclinical study of MSCs transplanting.

The invention aims to build an expression plasmid of a fusion protein hVE-cad-Fc of an extracellular structural domain segment of human blood vessel endothelium cadherins protein and an Fc segment of immunoglobulin G by utilizing a genetic engineering technology for the first time, and realize biosynthesis of hVE-cad-Fc fusion protein using eukaryotic cells. The fusion protein forms a stable hVE-cadhrin functional protein layer matrix on the material surface via Fc mediation, so that not only is the hydrophilia of hydrophobic materials improved, but also the property of the endothelial cell selective adhesion to the material surface is greatly improved; in addition, the expression of the endothelial cell proliferation and differentiation functions is improved. According to the invention, the isologous association of the hVE-cad-Fc fusion protein matrix and VE-cadherin positively expressed on the cell surface activates the intercellular adhesion link signal path, and through the synergistic effect with the blood vessel endothelium cell growth factors, the expression of the adhesion, proliferation, anti-apoptosis and differentiation functions of the blood vessel endothelium cells are regulated and controlled; the hVE-cad-Fc fusion protein provided by the invention can be used to improve the affinity of the material endothelium cells, promote the functional modification of artificial extracellular matrix subjected to tissue engineering vascularization / endothelialization and biomedical materials.

The invention belongs to the field of medicine and chemical engineering, and relates to an anti-apoptosis protein inhibitor and an application thereof, in particular to a heterocyclic alkane derivative and an application of the derivative taken as the anti-apoptosis protein inhibitor or used for preparing antitumor drugs. More specifically, the invention relates to a compound represented as a general formula I, and an isomer of the compound or the compound can be used as pharmaceutical salt. The compound can effectively inhibit activity of IAPs, and has potential of prevention and treatment of diseases such as tumors and the like.

The invention relates to a human Bcl-2 and human VEGF165 double-gene co-expression recombinant vector and a building method thereof, and is characterized in that IRES segment is utilized to connect an hBc1-2 gene and an hVEGF165 gene, and homologous recombination mechanisms in bacterium are utilized to recombine and build the human Bcl-2 and human VEGF165 double-gene co-expression recombinant vector according to an AdEasy system. The invention leads the Bcl-2 gene with anti-apoptosis capacity and the VEGF165 gene which currently promotes angiogenesis cytokine with strongest function to recombine on a same vector to be co-expressed, and solves the problem of low survival rate of transplanted cells under the condition of hypoxia and inflammation, simultaneously plays the function of promoting angiogenesis of VEGF165, plays an important part in the gene therapy of myocardial infarction and the cell transplantation research field, and has wide application prospect.

The invention discloses a human Vgamma9Vdelta2T cell proliferation method and a culture medium. Interleukin-15 and vitamin C are added in the proliferation culture process of human Vgamma9Vdelta2T cells, compared with a traditional proliferation method, the method can improve the proliferation efficiency and purity of the human Vgamma9Vdelta2T cells, and the cultured human Vgamma9Vdelta2T cells which have higher anti-apoptosis capacity and longer cell survival time at the same time have higher anti-apoptosis capacity, longer cell survival time and higher expression level of key killing molecules NKG2D and thus have high killing capacity for tumor cells.