1397results about How to "Promote apoptosis" patented technology

Compositions and methods are provided for modulating the expression of bcl-x. Antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding bcl-x are preferred. Methods of using these compounds for modulation of bcl-x expression and for treatment of diseases associated with expression of bcl-x are also provided. Methods of sensitizing cells to apoptotic stimuli are also provided.

Disclosed is an isomer, enantiomer, diastereoisomer or tautomer of a compound represented by Formula I: or a salt thereof, in which R1, R2, R100, R200, A, A1, B, B1, BG, n, Q and Q1 are substituents described. Also disclosed is the use of compounds of Formula 1 to treat proliferative disorders.

Disclosed is an isomer, enantiomer, diastereoisomer or tautomer of a compound represented by Formula I: or a salt thereof, in which R1, R2, R100, R200, A, A1, B, B1, BG, n, Q and Q1 are substituents described. Also disclosed is the use of compounds of Formula 1 to treat proliferative disorders.

The invention provides isolated agents having a core peptide selected from the group consisting of Core peptides 5 through 39 and 42 through 55, wherein the agent derepresses an IAP-inhibited caspase. Also provided is an isolated agent having a core structure selected from any of the structures shown in FIGS. 5, 9, 10, 14B, 21-24 and 48, a core structure selected from the group of TPI 759, TPI 882, TPI 914 or TPI 927; and a core structure from a library selected from TPI 1391, TPI 1349, TPI 1396, TPI 1509, TPI 1540, TPI 1400, TPI 792, TPI 1332, TPI 1567, TPI 1576 and TPI 1577, wherein the agent derepresses an IAP-inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase.

The invention relates to the technical field of application of bacteroides fragilis, and in particular relates to application of bacteroides fragilis in preparing a composition for preventing and treating colon cancer. Experiments show that bacteroides fragilis induces an organism to generate the anti-tumor effect in vivo, inhibit the tumor growth, accelerate tumor cell apoptosis and prolong the lifetime, so that bacteroides fragilis has a good effect in preventing and treating colon cancer. The invention explores novel use of bacteroides fragilis and develops a novel application field, thereby indicating that the bacteroides fragilis has good edible and officinal prospect. Bacteroides fragilis serving as probiotic can be used for preparing foods or medical compositions for preventing and treating colon cancer so as to provide a clinically health-care and preventing and treating food suitable for human to take.

The invention provides isolated agents having a core peptide selected from the group consisting of Core peptides 5 through 39 and 42 through 55, wherein the agent derepresses an IAP-inhibited caspase. Also provided is an isolated agent having a core structure selected from any of the structures shown in FIGS. 5, 9, 10, 14B, and 21-24 wherein said agent derepresses an IAP-inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase. The method consists of contacting an IAP-inhibited caspase with an effective amount of an agent to derepress an IAP-inhibited caspase, the agent having a core motif selected from the group consisting of a core peptide having a sequence set forth in any of Core peptides 4 through 39 and 42 through 55, and a core structure selected from the group consisting of TPI759, TPI882, TPI914 or TPI927. The methods of the invention also can be used for promoting apoptosis in a cell and for reducing the severity of a pathology characterized by reduced levels of apoptosis. Methods for identifying agents that derepress an IAP-inhibited caspase are also provided.

Compounds and pharmaceutical compositions containing the same are provided, which are useful in therapeutic treatment or prevention of various diseases.

The invention provides isolated agents having novel chemical structures and possessing superior activity as derepressors of IAP inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase. The invention further provides assay methods employing labeled compounds of the invention, especially fluorescent labeled compounds.

This invention pertains to certain carbamic acid compounds which inhibit HDAC (histone deacetylase) activity of the following formula: wherein: Cy is independently a cyclyl group; Q1 is independently a covalent bond or cyclyl leader group; the piperazin-1,4-diyl group is optionally substituted; J1 is independently a covalent bond or —C(═;O)—; J2 is independently —C(═O)— or —S(═O)2—; Q2 is independently an acid leader group; wherein: Cy is independently: C3-20carbocyclyl, C3-20heterocyclyl, or C5-20aryl; and is optionally substituted; Q1 is independently: a covalent bond; C1-7alkylene; or C1-7alkylene-X—C1-7alkylene, —X—C1-7alkylene, or C1-7alkylene-X—, wherein X is —O— or —S—; and is optionally substituted; Q2 is independently: C4-8alkylene; and is optionally substituted; and has a backbone length of at least 4 atoms; or: Q2 is independently: C5-20arylene; C5-20arylene-C1-7alkylene; C1-7alkylene-C5-20arylene; or, C1-7alkylene-C5-20arylene-C1-7alkylene; and is optionally substituted; and has a backbone length of at least 4 atoms; or a pharmaceutically acceptable salt, solvate, amide, ester, ether, chemically protected form, or prodrug thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.

The present invention pertains to certain imidazo[4,5-b]pyridin-2-one and oxazolo[4,5-b]pyridin-2-one compounds and analogs thereof, which, inter alia, inhibit RAF (e.g., B-RAF) activity, inhibit cell proliferation, treat cancer, etc., and more particularly to compounds of the formula (I): wherein: J is independently —O— or —NRN1—; RN1, if present, is independently —H or a substituent; RN2 is independently —H or a substituent; Y is independently —CH═ or —N═; Q is independently —(CH2)j-M-(CH2)k— wherein: j is independently 0, 1 or 2; k is independently 0, 1, or 2; j+k is 0, 1, or 2; M is independently —O—, —S—, —NH—, —NMe—, or —CH2—; each of RP1, RP2, RP3, and RP4 is independently —H or a substituent; and additionally RP1 and RP2 taken together may be —CH═CH—CH═CH—; L is independently: a linker group formed by a chain of 2, 3, or 4 linker moieties; each linker moiety is independently —CH2—, —NRN—, —C(═X)—, or —S(═O)2—; exactly one linker moiety is —NRN—, or: exactly two linker moieties are —NRN—; exactly one linker moiety is —C(═X)—, and no linker moiety is —S(═O)2—; or: exactly one linker moiety is —S(═O)2—, and no linker moiety is —C(═X)—; no two adjacent linker moieties are —NRN—; X is independently ═O or ═S; each RN is independently —H or a substituent; A is independently: C6-14carboaryl, C5-14heteroaryl, C3-12carbocyclic, C3-12heterocyclic; and is independently unsubstituted or substituted; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, N-oxides, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., B-RAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and conditions that are ameliorated by the inhibition of RAF, RTK, etc., proliferative conditions such as cancer (e.g., colorectal cancer, melanoma), etc.

The invention relates to a portable high-voltage nanosecond squarer which belongs to a medicinal device for inducing cancer cell apoptosis by using a high-voltage nanosecond square wave pulse electric field. The portable high-voltage nanosecond squarer mainly comprises a power supply system, a high-voltage direct current module, a low-voltage power supply, a pulse forming system and a pulse shaping and counting system. The portable high-voltage nanosecond squarer has output pulses with highest amplitude of 15kV, pulse width adjustment range of 50ns-1us, rising edge gradient of reaching 10ns and controllable recurrence frequency of 0.2-15Hz; and the quantity of the output pulses of the portable high-voltage nanosecond squarer can be set. The portable high-voltage nanosecond squarer can be adjusted in multiple-parameters (pulse amplitude, pulse width, recurrence frequency, pulse quantity and the like), large-range and flexible and independent way, and is beneficial to researching the optimal window parameter of the cancer cell apoptosis and promoting the cancer cell apoptosis as well as improving the cancer treatment effect. Meanwhile, the portable high-voltage nanosecond squarer has compact and light structure, reliable work, simple operation and convenient popularization and application, and can be widely applied to the treatment of various cancers.

The invention provides small molecule mimics of the Smac peptide that are dimer- or dimer-like compounds having two amide-containing domains connected by a linker. These compounds are useful to promote apoptosis. The invention includes pharmaceutical compositions comprising such compounds and methods to use them to treat conditions including cancer and autoimmune disorders.

The present invention provides a single-stranded circular RNA and DNA, and a preparation method and application thereof, the single-stranded circular RNA and DNA can adsorb a single-stranded circularRNA or a single-stranded circular DNA of miRNA, thereby overcoming the disadvantage that a traditional single-stranded RNA is easily degraded and has low efficiency, and can release tumor suppressor gene ''co-silencing'' caused by the miRNA. The single-stranded circular RNA or DNA prepared by the method can specifically adsorb the target miRNA so as to inhibit the proliferation, migration and invasion of tumor cells and promote the apoptosis of the tumor cells, can regulate the proportion of immune cells, has good anti-tumor and immune regulation effects, and is expected to be developed as a therapeutic drug for tumors or immune diseases.

This invention provides compounds including peptides and peptidomimetics that can be used to treat cell proliferative disorders, such as those associated with benign and malignant tumor cells. While the invention is not limited to any particular mechanism, the compounds of the invention appear to function at least in part by inhibiting G2 cell cycle checkpoint. Thus, invention compounds can be used to inhibit cell growth alone or be used in combination with a nucleic acid damaging treatment to inhibit cell growth.

Disclosed is an isomer, enantiomer, diastereoisomer or tautomer of a compound represented by Formula I: or a salt thereof, in which R1, R2, R100, R200, A, A1, B, B1, BG, n, Q and Q1 are substitutents described. Also disclosed is the use of compounds of Formula 1 to treat proliferative disorders.

The present invention is directed towards an isomer, an enantiomer, a diastereoisomer, or a tautomer of a pyrrolidine compound represented by Formula I:in which the substituents R1, R1a, R2, R2a, R3, A and Q are defined herein; or a prodrug, or a salt thereof, and which bind to IAP BIR domains. In particular, the compounds are useful in treating proliferative disorders such as cancer.

The present invention relates to method for depletion of CD137 positive cells using an anti-CD137 antibody-toxin complex, and more particularly, to a method for selective depletion of CD137 positive cells, comprising the step of contacting an anti-CD137 antibody-toxin complex with the CD137 positive cells. The method for selective depletion of CD137 positive cells in accordance with the present invention can be useful to prevent or treat various diseases including immune diseases mediated by the activation of the CD137 positive cells because this method is excellent in delivering a complex of an anti-CD137 antibody, specific to CD137 molecules, and a toxin to CD137 expressing cells and selectively killing the CD137 positive cells alone and is also excellent in suppressing cell proliferation.

Endoplasmic reticulum stress has been found to be associated with the genetic disease tuberous sclerosis. Tuberous sclerosis is cause by defects in the two genes, TSC1 and TSC2. Agents that modulate ER stress may be used to treat tuberous sclerosis and other hamartomatous diseases. In particular, 4-phenyl butyric acid (PBA) has been shown to reduce ER stress is TSC-deficient cells. Other compounds useful in reducing ER stress are chemical chaperones such as trimethylamine N-oxide arid glycerol may also be useful in treating tuberous sclerosis. The present invention provides methods of treating a subject suffering from tuberous sclerosis using ER stress reducers such as PBA, TUDCA, UDCA, and TMAO. Methods of screening for ER stress reducers by identifying agents that reduce levels of ER stress markers in TSC-deficient cells are also provided. These agents may find use in methods and pharmaceutical compositions for treating tuberous sclerosis.

The invention belongs to the genetic engineering field, and especially relates to an application of long-chain non-coding RNA in the preparation of non-small cell lung cancer treatment drugs. The change of the lnc-uc002llc.1 expression has influences on the apoptosis, proliferation, the drug susceptibility and the like of non-small cell lung cancer cells, so the reduction of the lnc-uc002llc.1 expression can realize the apoptosis promotion, proliferation inhibition and chemotherapy drug susceptibility enhancement of the non-small cell lung cancer cells.

Endoplasmic reticulum stress has been found to be associated with the genetic disease tuberous sclerosis. Tuberous sclerosis is cause by defects in the two genes, TSC1 and TSC2. Agents that modulate ER stress may be used to treat tuberous sclerosis and other hamartomatous diseases. In particular, 4-phenyl butyric acid (PBA) has been shown to reduce ER stress is TSC-deficient cells. Other compounds useful in reducing ER stress are chemical chaperones such as trimethylamine N-oxide arid glycerol may also be useful in treating tuberous sclerosis. The present invention provides methods of treating a subject suffering from tuberous sclerosis using ER stress reducers such as PBA, TUDCA, UDCA, and TMAO. Methods of screening for ER stress reducers by identifying agents that reduce levels of ER stress markers in TSC-deficient cells are also provided. These agents may find use in methods and pharmaceutical compositions for treating tuberous sclerosis.

Disclosed is a pharmacological composition for treating cancer cells, comprising solamargine and a pharmacologically compatible carrier or diluent.

Methods and small molecule compounds for inhibition of cancer cell proliferation are provided. One example of a class of compounds that may be used is represented by the compound of Formula I or a pharmaceutically acceptable salt, N-oxide or solvate thereof, wherein A, B, D, E, F, G, I, J, R, R1, R2, R2′, R3, R4, R5, R6, R7, R8, R9 are as described herein.

The invention discloses application of ginkgolide B to preparation of medicament for preventing and / or treating autosomal dominant polycystic kidney disease. A madin-darby canine kidney (MDCK) vesicle model is used for screening to find that the ginkgolide B inhibits formation and growth of vesicles. An experimental result shows that: the ginkgolide B has an obvious inhibiting effect on the formation and growth of MDCK vesicles and the effect of the ginkgolide B is in dose response relationship; the ginkgolide B has no cytotoxicity to MDCK cells, so that the vesicle inhibiting effect of the ginkgolide B is independent of the cytotoxicity; the ginkgolide B does not obviously induce MDCK cell apoptosis, so that the vesicle inhibiting effect of the ginkgolide B is independent of cell apoptosis promotion of the ginkgolide B; the ginkgolide B can promote the MDCK cells or vesicles to form tubular structures; and the effect is in dose response relationship; and the ginkgolide B has an inhibiting effect on the growth of the embryonic kidney vesicles. The ginkgolide B provides experimental data for development of a specific medicament for preventing and / or treating autosomal dominant polycystic kidney disease.

The invention relates to the technical field of biological control of breast cancer disease and discloses a polypeptide for promoting apoptosis of breast cancer cells by targeted uptake of siRNA. Thepolypeptide comprises a polypeptide 1; the sequence of the polypeptide 1 is H-Ile-Phe-D-Trp-Leu-Leu-Trp-Gln-Gly-Arg-Gly-Gly-Gly-Arg-Arg-Arg-Arg-Arg-Arg-Arg-OH. A detection method for the polypeptide for promoting the apoptosis of the breast cancer cells by targeted uptake of the siRNA comprises the following steps: firstly, culturing the breast cancer cells: selecting breast cancer cells MDA-MB-231, culturing the breast cancer cells MDA-MB-231 by adopting a DMEM culture medium, and sequentially adding 10 percent of fetal calf serum, 100 unit / ml of penicillin and 100g / mL of streptomycin in theculture medium. According to the polypeptide for promoting the apoptosis of the breast cancer cells by targeted uptake of the siRNA, the polypeptide 1 wraps the siRNA to form nanoparticles for targeting delivery of the siRNA to the breast cancer cells; the nanoparticles can realize the targeting delivery of the siRNA through a surface receptor of the breast cancer cells and have little damage to normal cells, and the practicality of the polypeptide is improved; meanwhile, the targeting delivery of TRPC1 siRNA by using the polypeptide 1 causes the apoptosis of the breast cancer cells, so that the effect of treating breast cancer is realized.

The invention discloses a beta-carboline derivative containing hydroximic acid as well as a preparation method and a medical application thereof. The product has the structure as shown in the general formula I. The compound can be combined with other antitumor drugs such as alkylating agents, antimetabolites, topoisomerase inhibitors, mitotic inhibitors and DNA intercalating agents and additionally can be combined with radiotherapy. The invention also discloses a pharmaceutical composition containing the compound with the general formula I as well as medical application thereof, particularly application of preparation of antitumor medicines, Alzheimer disease medicines and Parkinson disease medicines. The other antitumor medicines or radiotherapy can be administrated with the compound at the same time or in different times. The combination therapy can generate the synergistic effect, so that the treatment effect is improved.

The invention belongs to the technical field of RNA interference, and discloses TGF-beta specific siRNA containing a free triphosphoric acid group and application thereof. The 5' ends of antisense strand and sense strand sequences of the TGF-beta specific siRNA containing the free triphosphoric acid group are guanosine, and the free triphosphoric acid group is modified on the pentose 3' site of the guanosine. By combining the TGF-beta specific gene silencing mechanism and the antiviral inherent immune mechanism of an induced eukaryotic cell, the siRNA can inhibit important molecule TGF-beta of mediated tumor immunologic escape, effectively activate the anti-tumor immunity of the body and remarkably improve the effect of treating tumor. The siRNA effectively solves the problem that the traditional siRNA (OH-RNA) only has single gene silencing function but poor tumor treatment effect. The ppp-TGF-beta can be applied to preparing a medicament for treating the tumor, in particular pancreatic cancer.

The invention provides an anti-B7H3 chimeric antigen receptor and application thereof. The anti-B7H3 chimeric antigen receptor comprises an antigen binding domain, a hinge region, a transmembrane domain and a signal transduction domain, wherein the antigen binding domain is an anti-human B7H3 antibody. The anti-B7H3 chimeric antigen receptor has a specific targeting effect on B7H3 positive tumor cells, T cells expressing the anti-B7H3 chimeric antigen receptor have a remarkable in-vitro and in-vivo killing effect, the B7H3 positive tumor cells can be effectively removed, and the anti-B7H3 chimeric antigen receptor has important significance in the field of tumor treatment.

The invention discloses antibodies that bind high specificity to human RANKL (Receptor Activator for Nuclear Factor kappa B Ligand), wherein, the antibodies are used for the treatment of bone erosion caused by astogeny, hormonotherapy, postmenopausal osteoporosis, bone metastasis, and inflammation. The invention also discloses DNA sequences and supposed amino acid sequences of the antibodies.