Abstract: The invention relates to fusion proteins and bacteria encoding them. The fusion proteins include a ligand-binding domain interposed between the splicing domains of an intein. An auxotroph-relieving protein domain is fused to one of the splicing domains so that the auxotroph-relieving function of the domain is activated upon ligand binding. The fusion proteins can be expressed in bacterial cells and used as sensors of binding of compounds with the ligand-binding domain of proteins such as the human estrogen receptors or the human thyroid hormone receptor. The bacterially expressed fusion proteins can detect and report agonist and antagonist activity characteristic of the naturally-occurring hormone with the ability to modulate the function of the protein from which the ligand-binding domain of the fusion protein is derived.

Abstract: Provided are thiadiazolidine compounds of formula I wherein R1 is an organic group having at least 8 atoms selected from C or O, which is not linked directly to the N through a —C(O)— and comprising at least an aromatic ring, and their pharmaceutical compositions. These compounds are selective GSK-3 inhibitors and have improved bioavailability. They are useful for the treatment of GSK-3 mediated diseases, among others Alzheimer's disease, type II diabetes, depression and brain injury.

Abstract: The present invention relates to methods and compositions for identifying covalent joining or modification of proteins. In particular, the present invention relates to covalent fluorescence complementation assays for the detection of modified (e.g., ubiquitinated) proteins. The present invention further relates to the use of such fluorescence complementation assays in drug screening and research applications.

Abstract: This present invention discloses disease-associated molecules and assays, which are useful for diagnosing the presence or risk of developing osteoarthritis (OA) or related conditions. The invention has practical use in the early diagnosis of disease, in monitoring mammals at risk of developing OA, and in enabling better treatment and management decisions to be made in clinically and sub-clinically affected animals.

Abstract: A method for performing an immunoassay is described. The method is particularly useful for detecting extracellular polysaccharide (EPS) and/or lipopolysaccharide (LPS) producing microorganisms. The method is particularly useful for detecting microorganisms which produce extracellular polysaccharides (EPS) also known as exocellular polysaccharides, capsule, and/or lipopolysaccharides (LPS). In a preferred method for detecting microorganisms which produce EPS, LPS, or both, the EPS and/or LPS is extracted from a sample with cetyltrimethylammonium bromide (CTAB) to produce molecular aggregates which are then preferentially bound to colored polystyrene latex particles over other components in the sample, and the bound EPS and/or LPS detected using a lateral flow immunoassay apparatus which has immobilized thereon antibodies specific for the EPS and/or LPS. The method can also be used to detect particular viruses, for example viruses of the potyviridae or tobamoviridae group.

Abstract: The present invention relates to a method to identify substances and a use of such substances which can modulate IL-4 dependent signaling involved in tumor diseases, preferably Hodgkin Lymphomas or inflammatory airway diseases, preferably asthma and a method for determining whether a substance can modulate the interaction of STAT6 with NCoA-1, characterized in that a) STAT6 or fragments or derivatives thereof having the ability to bind to NcoA-1 are brought into contact with NCoA-1 or fragments or derivatives of NCoA-1 having the ability to bind STAT6 under conditions where STAT6 and NCoA-1 or said fragments or derivatives are capable of forming a complex, and said complex can be used to induce a measurable readout; b) a readout is measured in the absence or presence of the substance of interest; c) the readout in absence of substance of interest is compared with readout in presence of substance of interest.

Abstract: The invention provides in a first aspect a method for the identification of an LRRK2 interacting compound, comprising the steps of providing a protein preparation containing LRRK2, contacting the protein preparation with indol ligand 91 immobilized on a solid support under conditions allowing the formation of an indol ligand 91-LRRK2 complex, incubating the indol ligand 91-LRRK2 complex with a given compound, and determining whether the compound is able to separate LRRK2 from the immobilized indol ligand 91. Furthermore, the invention relates to a method for the identification of an LRRK2 interacting compound, comprising the steps of providing a protein preparation containing LRRK2, contacting the protein preparation with indol ligand 91 immobilized on a solid support and with a given compound under conditions allowing the formation of an indol ligand 91-LRRK2 complex, and detecting the indol ligand 91-LRRK2 complex.

Abstract: The invention discloses nearly 480 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, and provides phosphorylation site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose.

Abstract: The invention is a procedure for measuring the binding of an entity (ligand) to a surface by using a hapten-conjugated version of the ligand (hapten-ligand). An excess of the hapten-ligand is presented to the binding surface and excess (unbound) hapten-ligand is washed off. Bound hapten-ligand is then solubilized (removed) and applied to a membrane support or separated by electrophoresis and applied to a membrane support. Known amounts of hapten-ligand are similarly applied to the membrane, to provide for hapten-ligand standards. The membrane-bound hapten-ligand is detected by application of an enzyme-conjugated antibody to the hapten; or by application of an antibody to the hapten followed by application of an enzyme-conjugated antibody to the anti-hapten antibody. The resultant membrane-associated enzyme is detected and quantitated by the application of a color or light-producing substrate which reacts with the enzyme.

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like and PGPH activities of the 20S proteasome can be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus, such as a detectable label. Along with therapeutic utilities, these peptide based compounds can be used in assays useful for screening, monitoring, diagnostic and/or dosing purposes.

Abstract: The screening method for an anticancer drug comprises selecting a compound which blocks the kinase activity of TNIK, or blocks the combination of TNIK with ?-catenin/TC4 transcription complex.

Abstract: The invention provides molecules containing nucleic acid sequences for fragments of LPS-induced TNF-? factor (LITAF) and vectors containing these sequences. Also provided are molecules that contain the peptide sequence SQTWREPGAAGSPFHL, or homologs thereof. Such molecules may be useful in the treatment of diseases that relate to the expression of TNF-?, where treatment involves the modulation of this expression. The invention also provides methods for identifying compounds that inhibit or enhance the transcription of TNF-?.

Abstract: Method for the qualitative and semi-quantitative detection of a ligand in a sample of a medium to be tested, by (1) diluting at least one lyophilized reaction medium in said sample, (2) incubating the sample in order to carry out an immunoenzymatic method, and (3) observing the resulting colouration.

Abstract: The present invention is directed to novel polypeptides having homology to a polypeptide suppressor of the Drosophila melanogaster fused protein and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

Abstract: Modulation of cytochrome c acetylation, e.g., with a SIR polypeptide, enables interventions that modulate lifespan regulation and cell proliferation, e.g., by modulating apoptosis and/or mitochondrial function such as respiration.

Abstract: Disclosed are protein biomarkers and their use in diagnosing lung cancer or to make a negative diagnosis in patients. Also disclosed are kits for the diagnosis of lung cancer that detect the protein biomarkers of the invention, as well as methods using a plurality of classifiers to make a probable diagnosis of lung cancer. In certain aspects of the invention, the methods include use of a decision tree analysis. Various computer readable media and their use according to the invention are also disclosed.

Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein: X is CH or N; and R4 is optionally substituted C3-8 alkyl or optionally substituted C3-8 cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

Abstract: The present invention relates to the use of TROY, also called tumor necrosis factor receptor superfamily, member 19 (TNFRSF 19) also called toxicity and JNK inducer (TAJ), in diagnosis and therapy of non-epithelial cancers, such as melanoma. Accordingly, the invention provides in vitro and in vivo diagnostic and/or prognostic methods for cancers, other than epithelial cancers, preferably melanoma, comprising analyzing TROY expression in a biological sample from an individual or in an individual, wherein expression of TROY in non-epithelial cells, such as in melanocytes, in indicative the biological sample or the individual containing malignant cells, such as malignant melanoma cells. The invention also provides therapeutic use of TROY targeting molecules, such as TROY antibodies or TROY targeting RNA interfering agents for treatment of cancer wherein the cancer cells express TROY.

Abstract: The present invention relates to inhibitors of mitochondrial F1F0-ATPase, methods for their discovery, and their therapeutic use. In particular, the present invention provides the compound PK11195 and structurally and functionally related compounds as F1F0-ATPase inhibitors, and methods of using such inhibitors as therapeutic agents to treat a number of conditions.

Abstract: A crystalline structure of glutaminyl cyclase (QC) is described. Also described are the methods of preparing the crystalline structure of QC and the methods for identifying candidate inhibitors of QC. In addition, a structural basis for the rational design or identification of new inhibitors that may be used to treat QC-associated disorders is also described.

Abstract: The present invention provides methods for screening for a molecule that antagonizes or agonizes RANK activity. One aspect of the invention involves the growth of RANK responsive cells in semi-solid medium, wherein exposure to a RANK antagonist promotes colony formation. Other aspects of the invention rely on promoter/reporter constructs using RANK responsive promoters derived from the MMP-9 and TRAP genes. Additional aspects of the invention exploit the ability of RANK to activate c-src activity, F-actin ring formation and CaPO4 resorption.

Abstract: The present invention provides a method of measuring the activity of neprilysin, etc. More specifically, the present invention provides a method of measuring the activity of neprilysin in nerve cells; a method of screening a protein, a peptide or a compound enhancing the activity or expression of neprilysin nerve cells by measuring the activity of neprilysin; a method of enhancing the activity or expression of neprilysin; and so on. Thus, the compound enhancing the activity and/or expression of neprilysin, which is obtained by the screening method characterized by using the method of measuring the activity of neprilysin in accordance with the present invention, is useful as a preventive and/or therapeutic agent for Alzheimer's disease. The method of measuring the activity of the present invention can be used for presymptoms diagnosis of Alzheimer's disease.

Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein: X is CH or N; one of R1 and R2 is H, and the other is selected from OR6, SR6, NR6R7, N3, Me, Et, CF3, SOR8 and SO2R8; R3 is selected from tert-butylmethyl, iso-propylmethyl, sec-butyl, tert-butyl, cyclopentyl and cyclohexyl; R4 is optionally substituted C1-8 alkyl or optionally substituted C3-8 cycloalkyl; R6 and R7 are each independently selected from H, C1-8-alkyl and C3-8-cycloalkyl, or R6 and R7 are linked to form a cyclic group together with the nitrogen to which they are attached; and R8 is C1-8-alkyl or C3-8-cycloalkyl.

Abstract: T cell receptors (TCRS) that have higher affinity for a ligand than wild type TCRs are provided. These high affinity TCRs are formed by mutagenizing a T cell receptor protein coding sequence to generate a variegated population of mutants of the T cell receptor protein coding sequence; transforming the T cell receptor mutant coding sequence into yeast cells; inducing expression of the T cell receptor mutant coding sequence on the surface of yeast cells; and selecting those cells expressing T cell receptor mutants that have higher affinity for the peptide/MHC ligand than the wild type T cell receptor protein. The high affinity TCRs can be used in place of an antibody or single chain antibody.

Abstract: Hypoxia, a state of lower than normal tissue oxygen tension, has recently been implicated in a host of human diseases, including cancer, heart disease, and neurological disorders. Novel associations between p97 and other proteins, including UBX-domain-containing proteins (UBX-polypeptides), HIF1?, and a variety of E3 ligases are provided herein. The disclosure provides complexes comprising UBX-domain-containing polypeptides (UBX-polypeptides) and other polypeptides involved in the degradation of ubiquitinated proteins. In addition, the disclosure provides uses for active agents that modulate protein-protein complex formation between an UBX-polypeptide and its complementary-binding substrate. For example, the disclosure provides methods for treating or preventing hypoxia-related disorders or conditions in a patient or a cell by administration of an active agent that modulates the activity of an UBX-polypeptide and/or its complementary binding-substrate.

Abstract: A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof, wherein: one of R1 and R2 is H, and the other is selected from OR6, SR6, NR6R7, N3, Me, Et, CF3, SOR8 and SO2R8; or R1 and R2 are both H; one of R3 and R4 is H, and the other is selected from tert-butylmethyl, iso-propylmethyl, sec-butyl, tert-butyl, cyclopentyl and cyclohexyl; or R3 and R4 are joined together with the adjacent backbone carbon atom to form a spiro-C5-C6 cycloalkyl group; R6 and R7 are each independently selected from H, C1-8-alkyl and C3-8-cycloalkyl; or R6 and R7 are linked to form a cyclic group together with the nitrogen to which they are attached; R8 is C1-8-alkyl or C3-8-cycloalkyl; R9 is a para-substituted 6-membered monocyclic aryl or heteroaryl ring which includes up to five heteroatoms.

Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein: R3 is ten-butylmethyl, sec-butyl or tert-butyl; X is CH or N; and R4 is optionally substituted C1-8 alkyl or optionally substituted C3-8 cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

Abstract: A method and kit for detecting the early onset of renal tubular cell injury, utilizing NGAL as an early urinary biomarker. NGAL is a small secreted polypeptide that is protease resistant and consequently readily detected in the urine following renal tubule cell injury. NGAL protein expression is detected predominantly in proximal tubule cells, in a punctate cytoplasmic distribution reminiscent of a secreted protein. The appearance NGAL in the urine is related to the dose and duration of renal ischemia and nephrotoxemia, and is diagnostic of renal tubule cell injury and renal failure. NGAL detection is also a useful marker for monitoring the nephrotoxic side effects of drugs or other therapeutic agents.

Abstract: The present invention provides a metal chelator and methods that facilitate binding, detecting, monitoring and quantitating of zinc ions in a sample. The metal chelating moiety of the zinc-binding compound is an analog of the well-known calcium chelator, BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N?,N?-tetraacetic acid), wherein the chelating moiety has been modified from a tetraacetic acid moiety to a tri- di- or monoacetic moiety. This change in acetic acid groups on the metal chelating moiety results in the selective bindings of zinc ions in the presence of calcium ions, both of which are present in biological fluids and intracellular cytosolic fluid and organelles.

Abstract: The invention encompasses agents and their methods of use for modulating the activity of kinases by effecting their acetylation or their binding to nucleic acids. The invention thus encompasses the modulation of S6 kinase by effecting its acetylation by p300. The invention further encompasses the modulation of S6 kinase 2 by affecting its binding to DNA.

Abstract: The present invention relates to a polypeptide monobody which includes a modified acid sequence and renders the polypeptide monobody able to bind selectively to ???3 integrin. Fusion proteins and conjugates which include the polypeptide monobody, as well as compositions containing the polypeptide monobody, fusion proteins, or conjugates are also disclosed. Uses thereof include: treating or preventing an ???3 integrin-mediated disease or disorder, inhibiting ???3 integrin activity, treating a cancerous or precancerous condition, imaging tissues using positron emission tomography or magnetic resonance imaging, assessing the metastatic characteristics of a tumor, and delivering DNA to a cell.

Abstract: Disclosed are therapeutic treatment methods, compositions and devices for maintaining neural pathways in a mammal, including enhancing survival of neurons at risk of dying, inducing cellular repair of damaged neurons and neural pathways, and stimulating neurons to maintain their differentiated phenotype. In one embodiment, the invention provides means for stimulating CAM expression in neurons. The invention also provides means for evaluating the status of nerve tissue, including means for detecting and monitoring neuropathies in a mammal. The methods, devices and compositions include a morphogen or morphogen-stimulating agent provided to the mammal in a therapeutically effective concentration.

Abstract: The x-ray crystal structure of human BACE or BACE-like proteins is useful for solving the structure of other molecules or molecular complexes, and identifying and/or designing potential modifiers of human BACE activity.

Abstract: (Problems) The main object of the present invention is to provide a screening method for selecting a substance affecting a bond between thioredoxin and MIF. (Means for Solving Problems) The present invention provides a screening method for selecting a test substance which strengthens a bond between a polypeptide of a thioredoxin family and a macrophage migration inhibition factor, comprising: mixing a test substance with at least one binding substance selected from following (1) to (4), (1) the polypeptide belonging to the thioredoxin family, (2) a protein having an amino acid sequence of the polypeptide belonging to the thioredoxin family in which one or more amino acid is deleted, replaced or added, and having an equivalent activity to the polypeptide of the thioredoxin family, (3) a gene coding (1), (4) a gene coding (2); bonding the binding substance to the macrophage migration inhibition factor; and monitoring the bond state between the binding substance and the macrophage migration inhibition factor.

Abstract: A method for screening a test compound for activity in modulating the activity of the chloride channel ClC-7 either directly or by modulating the subcellular localization of Ostm1 comprises determining whether test compound inhibits the binding of Ostm1 to ClC-7. Compounds active in the screen are candidates for use in treating bone resorption conditions such as Osteoporosis by modulating the activity of osteoclasts.

Abstract: The invention relates to various intraflagellar transport (IFT) polypeptides and the nucleic acids that encode them. The new IFT particle polypeptides and nucleic acids can be used in a variety of diagnostic, screening, and therapeutic methods.

Abstract: Disclosed are DNA encoding a polypeptide which can modulate the activity of a muscle-specific tyrosine kinase, and others. The DNA is selected from the following members (a) to (d): (a) DNA comprising a specific nucleotide sequence; (b) DNA comprising a nucleotide sequence capable of hybridizing with a specific nucleotide sequence under stringent conditions; (c) DNA comprising a nucleotide sequence encoding an amino acid sequence having the substitution, deletion and/or addition of one or several amino acid residues in a specific amino acid sequence; and (d) DNA comprising a nucleotide sequence having 90% or higher homology to a specific nucleotide sequence.

Abstract: There is provided a biosensor capable of increasing a detecting sensitivity of a target substance of glutamate, by using a nano wire having excellent electrical characteristics and by immobilizing a receptor of glutamate to be detected on a substrate which is disposed between a nano wire and another nano wire and a method for manufacturing the same. The biosensor for detecting glutamate according to the present invention can be manufactured with an arrangement in which the nano wire is selectively arranged on a solid substrate in a matrix. Since this biosensor can prevent the degradation of the nano wire in the electrical characteristic, it can sensitively detect glutamate even through a small amount thereof is contained in a food so that it can be effectively used in detecting the food additive existing in the processed foodstuffs.

Abstract: A crystallized human ACC2 CT protein as well as a description of the X-ray diffraction pattern of the crystal are disclosed. The diffraction pattern allows the three dimensional structure of human ACC2 CT to be determined at atomic resolution so that ligand binding sites on human ACC2 CT can be identified and the interactions of ligands with human ACC2 CT amino acid residues can be modeled. Models prepared using such maps permit the design of ligands which can function as active agents which include, but are not limited to, those that function as inhibitors of human ACC2 and human ACC1 proteins.

Abstract: The present invention describes a polypeptide, comprising the amino acid sequence APAHRSSTFPKWVTKTERGRQPLRS (Seq. ID. No. 1) or a fragment thereof, said fragment comprising at least 7 consecutive amino acid residues of Seq. ID. No. 1.

Abstract: A probe comprises: (1) a target binding site moiety which is attached to a first fluorescent polypeptide; (ii) a mimic moiety which is capable of binding to the target binding site moiety and is attached to a second fluorescent polypeptide; and (iii) a linker which connects the two fluorescent polypeptides and which allows the distance between said fluorescent polypeptides to vary, said fluorescent polypeptides being so as to display fluorescence resonance energy transfer (FRET) between them, wherein the linker comprises one or more of: (1) a sequence capable of being recognised and bound by an immobilized component; (2) a protease cleavage site; (3) a non-analyte binding site; (4) two or more copies of the sequence (SerGly3); or (5) one or more copies of a rod domain from a structural protein.

Abstract: The present invention provides target proteins and target genes for bioactive substances such as drugs, and means that enable the development of novel bioactive substances using the same. More specifically, the present invention provides target proteins and target genes for bioactive substances; screening methods for substances capable of regulating bioactivities; bioactivity regulators; a bioactive substance derivative production method; a complex comprising a bioactive substance and a target protein, and a method of producing the complex; and kits comprising a bioactive substance or a salt thereof; determination methods for the onset or risk of onset of a specified disease or condition, determination methods for susceptibility to a bioactive substance, and determination kits used for the determination methods, and the like.

Abstract: A device for collecting and transporting aqueous fluid from the oral cavity to a lateral chromatographic strip for test is disclosed. The lateral chromatographic strip is placed within and extend along a cavity defined in a housing. At least one inspection site to the lateral chromatographic strip is provided to enable inspection of selected sites on the lateral chromatographic strip for test results. A porous wick material protrudes from the housing to a collection site exterior of the housing at one end and communicates to the lateral chromatographic strip at the other end. The porous wick material has particulate construction, the particles adsorbing aqueous oral fluid to transport the fluid from the mouth to the lateral chromatographic strip without substantial absorption. The particles of the porous wick material are bound together to define a continuous interstitial volume for the flow of oral fluid to be transported and are treated to be hydrophilic to the adsorbed oral fluids.

Abstract: Immunogenic T-cell receptor gamma Alternate Reading Frame Protein (TARP) polypeptides are disclosed herein. These immunogenic TARP polypeptides include nine consecutive amino acids of the amino acid sequence set forth as SEQ ID NO: 9 and do not comprise amino acids 1-26 or amino acids 38-58 of SEQ ID NO: 1. Several specific, non-limiting examples of these polypeptides are set forth as SEQ ID NOs: 3-7. Nucleic acids encoding these polypeptides, and host cells transfected with these nucleic acids, are also disclosed. Methods of using these polypeptides, and polynucleotides encoding these polypeptides, for the treatment of breast and prostate cancer are also disclosed.

Abstract: The present invention relates to selected substituted pyrimidines their preparation, pharmaceutical compositions containing them and their use as inhibitors of one or more protein kinases, and hence their use in the treatment of proliferative disorders, viral disorders and/or other disorders.

Abstract: The present invention provides a device/kit and methods of use thereof in rapid detection of target molecule binding to a cognate binding partner. The methods, inter-alia, make use of a device comprising channels or reservoirs, which are linked to nanochannels, whereby upon application of the cognate binding partner to the nanochannel comprising the target molecule under flow, a detectable change in conductance, capacitance or fluorescence or surface potential occurs.

Abstract: The invention provides a human SGK1 which is associated with cardiovascular diseases, cancer, endocrinological diseases, metabolic diseases, inflammation, gastroenterological diseases, hematological diseases, respiratory diseases, neurological diseases and urological diseases. The invention also provides assays for the identification of compounds useful in the treatment or prevention of cardiovascular diseases, cancer, endocrinological diseases, metabolic diseases, inflammation, gastroenterological diseases, hematological diseases, respiratory diseases, neurological diseases and urological diseases. The invention also features compounds which bind to and/or activate or inhibit the activity of SGK1 as well as pharmaceutical compositions comprising such compounds.

Abstract: This invention provides a novel bacterial sialic acid transporter that is a member of the family of ABC transporters. The transporter is a useful target for pharmaceuticals.

Abstract: Disclosed are methods for identifying agents which modulate the activity of bone morphogenetic protein-7. These methods for identifying agents utilize bone morphogenetic protein receptors, specifically the daf-4 receptor, and more specifically the extracellular domain of the daf-4 receptor. Agents identified by the methods are also described as well as compositions comprising the agents and methods of treating a subject using the agents or compositions.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to a novel ecdysone receptor/chimeric retinoid X receptor-based inducible gene expression system and methods of modulating gene expression in a host cell for applications such as gene therapy, large-scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation traits in transgenic organisms.