摘要:
The present invention is directed to gambogic acid, analogs and derivatives thereof, represented by the general Formulae I-III: wherein R1-R5 are defined herein. The present invention also relates to the discovery that compounds having Formula I-III are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled cell growth and spread of abnormal cells occurs.
摘要:
The present invention is directed to derivatives of gambogic acid and analogs thereof. Exemplary gambogic acid derivatives of the present invention include, among others, derivatives substituted in the C10 and C28 positions of gambogic acid. The present invention also relates to the discovery that certain preferred compounds of the present invention are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.
摘要:
The present invention relates to screening methods useful for drug discovery of apoptosis inducing compounds. In particular, the screening methodology relates to using Apoptosis Inducing Proteins (AIPs) as a target for the discovery of apoptosis activators useful as anticancer agents. The screening methods of the present invention can employ homogenous or heterogeneous binding assays using purified or partially purified AIPs; or whole cell assays using cells with altered levels of one or more AIPs. The invention also contemplates use of gambogic acid or GA-related compounds which bind AIPs and can accordingly be used to raise antibodies useful for drug discovery. Alternatively, labeled GA is used for competitive binding assays for drug discovery. Such assays afford high throughput screening of chemical libraries for apoptosis activators.
摘要:
The present invention pertains to a method of treating, preventing or ameliorating a disease responsive to induction of the caspase cascade in an animal, comprising administering to the animal a compound which binds specifically to a Tail Interacting Protein Related Apoptosis Inducing Protein (TIPRAIP). The present invention also relates to screening methods useful for drug discovery of apoptosis inducing compounds. In particular, the screening methodology relates to using TIPRAIP as a target for the discovery of apoptosis activators useful as anticancer agents. The screening methods of the present invention can employ homogenous or heterogenous binding assays using purified or partially purified TIPRAIP; or whole cell assays using cells with altered levels of TIPRAIP. The invention also contemplates use of 3-(4-azidophenyl)-5-(3-chloro-thiophen-2-yl)-[1,2,4]-oxadiazole or a substituted 3-aryl-5-aryl-[1,2,4]-oxadiazole which bind TIPRAIP and can accordingly be used to raise antibodies useful for drug discovery. Alternatively, labeled 3-(4-azidophenyl)-5-(3-chloro-thiophen-2-yl)-[1,2,4]-oxadiazole (or a labeled substituted 3-aryl-5-aryl-[1,2,4]-oxadiazole) is used for competitive binding assays for drug discovery. Such assays afford high throughput screening of chemical libraries for apoptosis activators.
摘要:
The present invention pertains to a method of treating, preventing or ameliorating a disease responsive to induction of the caspase cascade in an animal, comprising administering to the animal a compound which binds specifically to one or more Apoptosis Inducing Proteins (AIPs). AIPs include Transferrin Receptor Related Apoptosis Inducing Proteins (TRRAIPs), Clathrin Heavy Chain Related Apoptosis Inducing Proteins (CHCRAIPs), IQ motif containing GTPase Activating Protein Related Apoptosis Inducing Proteins (IQGAPRAIPs), and Heat Shock Protein Related Apoptosis Inducing Proteins (HSPRAIPs). The present invention also relates to screening methods useful for drug discovery of apoptosis inducing compounds. In particular, the screening methodology relates to using AIPs as a target for the discovery of apoptosis activators useful as anticancer agents. The screening methods of the present invention can employ homogenous or heterogenous binding assays using purified or partially purified AIPs; or whole cell assays using cells with altered levels of one or more AIPs. The invention also contemplates use of gambogic acid or GA-related compounds which bind AIPs and can accordingly be used to raise antibodies useful for drug discovery. Alternatively, labeled GA is used for competitive binding assays for drug discovery. Such assays afford high throughput screening of chemical libraries for apoptosis activators.
摘要:
A method for identifying therapeutically effective immunosuppressive agents by screening such agents for those which induce apoptosis in activated T cells is disclosed. T cells were isolated then activated and treating with various test compounds. A caspase substrate is added to detect caspase activation and apoptosis in the cells. Compounds which stimulate caspase activation and apoptosis are also tested against resting T cells to determine those agents which are more effective in activated T cells compared to resting T cells. Compounds with this selectivity are effective in treating immunopathological disorders such as arthritis, graft rejection, graft versus host disease, inflammatory bowel syndrome and the like.
摘要:
The present invention generally relates to disposable gloves, ethylene-based thermoplastic materials for use in preparing disposable gloves, and methods for preparing ethylene-based thermoplastic materials for use in preparing disposable gloves. In particular, the present invention relates to non-medical and non-surgical disposable gloves suitable for use in food-service and industrial applications.
摘要:
A plastic bag dispenser with side panels and guide bar includes: a) a base frame with a back and bottom section with open front adapted to hold a plastic bag roll; b) a swing arm and core rod adapted to receive a plastic bag roll for rotation and to move downwardly as the plastic bag roll is depleted; c) a first and second set of opposing side panels located on the base frame for stabilizing the movement of the plastic bag roll; d) an elongated open guide bar having a top and sides located on the open fronted bottom section for movement of bags from the plastic bag roll; and, e) a rip tongue located on the open fronted bottom section with an upward taper adapted to catch and separate a passing bag when pulled forward through the guide bar and over the rip tongue. Mounting mechanisms for the present invention are also detailed.
摘要:
A plastic bag dispenser with side panels and guide bar includes: a) a base frame with a back and bottom section with open front adapted to hold a plastic bag roll; b) a swing arm and core rod adapted to receive a plastic bag roll for rotation and to move downwardly as the plastic bag roll is depleted; c) a first and second set of opposing side panels located on the base frame for stabilizing the movement of the plastic bag roll; d) an elongated open guide bar having a top and sides located on the open fronted bottom section for movement of bags from the plastic bag roll; and, e) a rip tongue located on the open fronted bottom section with an upward taper adapted to catch and separate a passing bag when pulled forward through the guide bar and over the rip tongue. Mounting mechanisms for the present invention are also detailed.
摘要:
A stacked plastic film bag system includes a plurality of open top bags and at least one tongue for separating front and back panels of a bag that is next to be dispensed. Each bag has a header for maintaining the plurality of stacked open top bags in a mechanically pressed and/or heat-sealed. The tongue(s) extends below the front panel tops of the bags so as to permit a bag user to pull off a most forward bag wherein the front panel of the next sequential bag will be pulled forward so as to position in front of the tongue and will fall back to rest after complete removal of the most forward bag to effect interleafing of the tongue between the front panel and the back panel of each next sequential bag to ready it for easy removal and to inhibit static cling of the front and back panels.