101 results about "Retinoic acid receptor" patented technology

Methods of stimulating or increasing differentiation to regulatory T cells, cultures of regulatory T cells and methods of reducing or decreasing an immune response, inflammation or an inflammatory response, among other things, are provided. Methods include, among other things, contacting blood cells or T cells with an amount of TGF-beta or a TGF-beta analogue and a retinoic acid receptor agonist, or an amount of a retinoid X receptor (RXR) or peroxisome proliferator activated receptor-gamma (PPARgamma) agonist, sufficient to stimulate or increase differentiation to regulatory T cells. Cultures of regulatory T cells include T cells that express a marker associated with regulatory T cells, such as cultures in which regulatory T cells represent, for example, 30% or more of the total number of cells in the culture.

The present invention provides a therapeutic or prophylactic agent as a substitute for conventional steroids or immunosuppressive agents to treat or prevent systemic erythematosus, glomerulonephritis, lupus nephritis, idiopathic thrombocytopenic purpura or autoimmune anemia. The agent comprises a retinoic acid receptor agonist, specifically a retinoic acid receptor subtype alpha (RARalpha) agonist, including for example:(1) carboxylic acid compounds having condensed rings represented by the following formula: (wherein the rings L and M are condensed, are the same as or different from each other, and represent an aromatic hydrocarbon which may have a substituent group or a heterocycle which may have a substituent group; the rings A and B are independent of each other and represent an aromatic hydrocarbon ring or heterocycle which may have a substituent group; and D represents a carboxyl group which may have a protective group),(2) 4-{[(3,5-bistrimethylsilylphenyl)carbonyl]amino}benzoic acid, 4-{2-[5-(3-methoxymethyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene-2-yl)pyrrolyl]}benzoic acid, etc.

A composition is described comprising a vitamin D analog and a retinoid, wherein: (a) the vitamin D analog is capable of binding a vitamin D receptor or being converted in vivo into a compound capable of binding a vitamin D receptor; and (b) the retinoid is selected from the group consisting of a compound capable of binding a retinoic acid receptor, retinol in a concentration of at least about 0.1% and a compound in a concentration of at least about 0.% capable of being converted in vivo into retinol. Further, methods of treating disorders characterized by abnormal cell-proliferation and / or cell-differentiation are also described.

The invention provides in one embodiment a method for treating vascular trauma. The method can include administering to an individual undergoing vascular trauma an effective amount of a retinoic acid receptor (RAR) antagonist or an RAR inhibitor. The methods can be used to lower serum triglycerides in a patient undergoing an invasive vascular procedure such as vascular surgery.

Compounds, compositions, and methods for modulating processes mediated by Retinoid X Receptors using retinoid-like compounds which have activity selective for members of the subclass of Retinoid X Receptors (RXRs), in preference to members of the subclass of Retinoic Acid Receptors (RARs). Examples of such compounds are bicyclic benzyl, pyridinyl, thiophene, furanyl, pyrrole, and polyenoic acid derivatives including carbocyclic polyenoic acids. The disclosed methods employ compounds for modulating processes selectively mediated by Retinoid X Receptors.

The present invention provides a medicament exhibiting excellent retinoic acid receptor agonism. A Carboxylic acid derivative having a fused ring which is represented by the following formula or a pharmacologically acceptable salt thereof: {wherein the symbol represents a single bond or a double bond; X, Y, Z, P, Q, U, V and W are each a group represented by the formula: -O- or -S-, or a group represented by the formula: [wherein Rk (k: 1 to 8) is hydrogen, halogeno, optionally substituted lower alkyl or the like, with either of R7 and R8 being a group represented by the formula: (wherein A and B are each independently an optionally substituted aromatic hydrocarbon ring or an optionally substituted unsaturated heterocycle; and D is optionally protected carboxyl)]}.

The present embodiments relate to methods for the prevention and treatment of inflammatory conditions such as alcoholic liver disease (ALD). More specifically the present embodiments relate to the prevention and treatment of ALD through the administration of an Retinoic Acid Receptor (RAR) agonist. Some embodiments relate to use of tazarotene in the prevention and treatment of alcohol-induced liver injury, alcohol-related liver disease, fatty liver disease, hepatic steatosis, alcoholic hepatitis or alcoholic cirrhosis.

Compounds of the formula and compounds of the formula or their salts have the potent ability to bind to retinoic acid receptors thus useful in treating psoriasis and rheumatoid arthritis.

Proliferation of retinal pigment epithelium following surgery or trauma or resulting in ocular diseases associated with choroidal neovascularization, such as age related macular degeneration and histoplasmosis syndrome, is prevented by contacting retinal pigment epithelium cells with a therapeutic amount of a retinoic acid receptor (RAR agonist, preferably one with specific activity for retinoic acid receptors. Preferably the RAR agonist is also a potent antagonist of AP1-dependent gene expression. Alternatively, the proliferation of retinal pigment epithelium is ameliorated with a therapeutic amount of an AP-1 antagonist, alone or in combination with an RAR agonist. The drug can be administered by bolus injection into the vitreous cavity using a dosage from about 50 to 150 .mu.g. Or by slow release from liposomes or an oil tamponade injected into the vitreous cavity. Formulations for preventing proliferation of retinal pigment epithelium are also provided.

The invention provides retinoic acid receptor (RAR) selective agonists and formulations thereof for the treatment of disease or for inducing a medically beneficial effect.

PCT No. PCT / JP97 / 00852 Sec. 371 Date Aug. 20, 1998 Sec. 102(e) Date Aug. 20, 1998 PCT Filed Mar. 18, 1997 PCT Pub. No. WO97 / 34869 PCT Pub. Date Sep. 25, 1997The present invention provides a medicament exhibiting excellent retinoic acid receptor agonism. A Carboxylic acid derivative having a fused ring which is represented by the following formula or a pharmacologically acceptable salt thereof: {wherein the symbol +E,uns -----+EE represents a single bond or a double bond; X, Y, Z, P, Q, U, V and W are each a group represented by the formula: -O- or -S-, or a group represented by the formula: [wherein Rk (k:1 to 8) is hydrogen, halogeno, optionally substituted lower alkyl or the like, with either of R7 and R8 being a group represented by the formula: (wherein A and B are each independently an optionally substituted aromatic hydrocarbon ring or an optionally substituted unsaturated heterocycle; and D is optionally protected carboxyl)]}.

Disclosed herein are novel compounds with activity at RARβ 2 receptors. Further disclosed are the use of such compounds for treatment of or to alleviate symptoms of cancer, neurological disorders such as memory deficits and schizophrenia, neurodegenerative disorders such as Parkinson's and Alzheimer's diseases, inflammatory disorders such as psoriasis and rheumatoid arthritis, eye disorders and depression.

Oral and topical pharmaceutical compositions, kits and methods of treatment thereof for treating various skin disorder including acne, psoriasis, ichthyosis, photoaging, photodamaged skin, and, skin cancer. Exemplary vitamin D analogs as active pharmaceutical ingredients include 2-methylene-19-nor-20(S)-1α-hydroxy-bishomopregnacalciferol, 19-nor-26,27-dimethylene-20(S)-2-methylene-1α,25-dihydroxyvitamin D3, 2-methylene-1α,25-dihydroxy-(17E)-17(20)-dehydro-19-nor-vitamin D3, 2-methylene-19-nor-(24R)-1α,25-dihydroxyvitamin D2, 2-methylene-(20R,25S)-19,26-dinor-1α,25-dihydroxyvitamin D3, 2-methylene-19-nor-1α-hydroxy-pregnacalciferol, 1α-hydroxy-2-methylene-19-nor-homopregnacalciferol, (20R)-1α-hydroxy-2-methylene-19-nor-bishomopregnacalciferol, 2-methylene-19-nor-(20S)-1α-hydroxy-trishomopregnacalciferol, 2-methylene-23,23-difluoro-1α-hydroxy-19-nor-bishomopregnacalciferol, 2-methylene-(20S)-23,23-difluoro-1α-hydroxy-19-nor-bishomopregnancalciferol, (2-(3′hydroxypropyl-1′,2′-idene)-19,23,24-trinor-(20S)-1α-hydroxyvitamin D3, 2-methylene-18,19-dinor-(20S)-1α,25-dihydroxyvitamin D3, a stereoisomer thereof, a prodrug thereof in oral compositions, a salt thereof, and / or a solute thereof. Compounds that activate retinoic acid receptors, such as retinoyls and retinoyl esters, include 13-cis-retinoic acid, all-trans-retinoic acid, (2E,4E,6Z,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexeneyl)nona-2,4,6,8-tetraenoic acid, 9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-nona-2,4,6,8-tetraenoic acid, 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-napthoic acid, 4-[1-(3,5,5,8,8-pentamethyl-tetralin-2-yl)ethenyl]benzoic acid, retinobenzoic acid, ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)ethynyl]pyridine-3-carboxylate, retinoyl t-butyrate, retinoyl pinacol, retinoyl cholesterol, an isomer thereof, a prodrug thereof for oral compositions, an ester thereof, a salt thereof, and / or, a solute thereof. Combinations of such active ingredients demonstrate synergistic efficacy.

The invention discloses a recombinant adenovirus carrying a rat retinoic acid receptor (RAR) gamma gene. The gene of the recombinant adenovirus is derived from a rat mesenchymal stem cell and has an SEQID1 sequence. A construction method comprises the following steps: acquiring a target gene RAR gamma; constructing and identifying a recombinant adenovirus plasmid pAd-RAR gamma; and carrying out package, amplification, purification and titer detection on the recombinant adenovirus pAd-RAR gamma in a human embryonic kidney (HEK) 293 cell. In the invention, the rat mesenchymal stem cell can be efficiently infected and the RAR gamma gene can be efficiently expressed, thereby well solving the problem that a general eukaryotic vector is difficultly led in the RAR gamma cell through transfection of liposome; the physical and chemical properties of the used adenovirus vector are stable, thus preparation and operation are easy; the transfection efficiency of the gene is high, and exogenous gene expression level is high; and the obtained adenovirus is replication-defective, is not combined in a gene group of a host cell, has a high biological safety, and is widely suitable for various in vitro cells and in vivo experiment studies.

T cells are programmed to target the gastrointestinal tract by activation with dendritic cells capable of producing and / or transporting retinoic acid. Methods for using the programmed dendritic cells and / or T and / or B cells to treat a variety of pathogens and infectious agents residing in the intestine are also disclosed. Similarly, inhibitors of retinoic acid synthesis by dendritic cells or other cells in the gut, and inhibitors of retinoic acid receptors in T and / or B cells or other cells in the intestinal mucosa, are disclosed for treating a variety of gastrointestinal autoimmune diseases such as inflammatory bowel disease and celiac disease.

The present invention provides a method of more efficiently producing pancreas cells, particularly pancreatic hormone-producing cells, a method of stably producing pancreas cells in a large amount by more efficiently inducing differentiation of stem cells into pancreas cells, a medicament containing a pancreas cells and a screening method using the cells.A method of producing pancreatic hormone-producing cells, including subjecting stem cells to the following steps (1)-(4):(1) a step of cultivating stem cells in a medium containing an activator of activin receptor-like kinase-4,7 and a GSK3 inhibitor(2) a step of cultivating the cells obtained in the aforementioned step (1) in a medium containing an activator of activin receptor-like kinase-4,7(3) a step of cultivating the cells obtained in the aforementioned step (2) in a medium containing any one or more kinds selected from the group consisting of (a) retinoic acid receptor agonists, (b) at least one kind selected from the group consisting of inhibitors of AMP-activated protein kinase and / or activin receptor-like kinase-2,3,6, and BMP antagonists, and (c) inhibitors of activin receptor-like kinase-4,5,7(4) a step of cultivating the cells obtained in the aforementioned step (3).

The present invention relates to a method for obtaining a population of hepatic progenitor cells, said method comprising a step of culturing definitive endoderm cells with a culture medium stimulating hepatic specification. In a particular embodiment, such culture medium stimulating hepatic specification comprises a retinoic acid receptor (RAR) agonist, an FGF family growth factor and an inhibitor of the activin signaling pathway.

The invention relates to the field of pharmaceutical chemistry, and discloses nitric oxide donor tamibarotene derivatives and their preparation method and use. Specially, the invention provides nitric oxide donor tamibarotene derivatives shown in the structural general formula (I), wherein a definition of R is shown in the patent specification. The nitric oxide donor tamibarotene derivatives are a type of multi-target compounds prepared from Furoxan type nitric oxide donors and a retinoic acid receptor (RAR) agonist through heterozygosis of ester bonds or amide bonds of various connecting groups. The nitric oxide donor tamibarotene derivatives are suitable for being utilized as anti-tumor drugs for treating all types of leukemia.

The invention relates to medical therapy using an agonist of the retinoic acid receptor-related orphan receptor gamma (ROR gamma) and provides adoptive cellular therapies using an agonist of ROR gamma, populations of lymphocyte cells that have been exposed to an agonist of ROR gamma, populations of dendritic cells that have been exposed to an agonist of ROR gamma, pharmaceutical compositions, and methods for enhancing therapeutic effects of lymphocyte cells and / or dendritic cells in a patient by administering an agonist of ROR gamma to a patient.

The invention relates to a kit for the mRNA expression level of a PML-RARa fusion gene, and belongs to the field of biotechnology. The kit comprises a PML-RARa L fusion gene system, a PML-RARa V fusion gene system or a PML-RARa s fusion gene system and a reference gene system ABL, wherein each system comprises an upstream primer and a downstream primer and Taqman fluorescence probe. The PML-RARa fusion protein, as a variant retinoic acid receptor, has different DNA properties with a wild type RARa protein and is an intrinsic and effective repressor for retinoic acid (RA) signal which is the transcription factor of an intrinsic RARa target gene. Therefore, when the fluorescence quantitative polymerase chain reaction (PCR) method is used for detecting the mRNA expression level of the PML-RARa fusion gene, the detection result is more specific and sensible. The kit provides a novel quick and simple genetic diagnosis technology for predicting the prognosis of acute promyelocytic leukemia and determining chemotherapy regimens.

The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl-amido-aryl compounds of the following formula (for convenience, collectively referred to herein as “AAA compounds”), which, inter alia, are (selective) retinoic acid receptor α (RARα) agonists. 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 (selectively) activate RARα, and in the treatment of diseases and conditions that are mediated by RARα, that are ameliorated by the activation of RARα, etc., including cognitive disorders, memory impairment, memory deficit, senile dementia, Alzheimer's disease, early stage Alzheimer's disease, intermediate stage Alzheimer's disease, late stage Alzheimer's disease, cognitive impairment, and mild cognitive impairment.

A previously isolated hepatitis B virus (HBV) integration in a 147 bp cellular DNA fragment linked to hepatocellular carcinoma (HCC) was used as a probe to clone the corresponding complementary DNA from a human liver cDNA library. Nucleotide sequence analysis revealed that the overall structure of the cellular gene, which has been named hap, is similar to that of the DNA-binding hormone receptors. Six out of seven hepatoma and hepatoma-derived cell-lines express a 2.5 kb hap mRNA species which is undetectable in normal adult and fetal livers, but present in all non-hepatic tissues analyzed. Low stringency hybridization experiments revealed the existence of hap related genes in the human genome. The cloned DNA sequence is useful in the preparation of pure hap protein and as a probe in the detection and isolation of complementary DNA and RNA sequences. The hap protein is a retinoic acid (RA) receptor identified as RAR-β.

The invention discloses multiple-target-point tamibarotene derivatives, a preparation method and purposes thereof. More specifically speaking, the invention provides a compound represented by a structural general formula (I), wherein the definition of R is referred to an instruction book; the derivatives are multiple-target-point compounds which are obtained by connecting tamibarotene as an RAR (retinoic acid receptors) excitant with various histone deacetylase inhibitors, various RXR (retinoid X receptors) excitants or other pharmacophoric groups directly through ester bonds or amido bonds or indirectly through connecting groups; and the derivatives are suitable to be used as antitumor drugs to be used for treating various malignant tumors, and are particularly suitable for treating various leukemia.

Reprogrammed somatic cells, methods for reprogramming, reprogramming factors for somatic cells and uses of such factors and cells are described. Nuclear reprogramming factors [NRF] described comprise one or more of a gene product or a polynucleic acid encoding a gene product from a retinoic acid receptor (RAR / RXR) family member, or an agonist or antagonist thereof; a gene product from an Lrh1 family member; or an agonist thereof; retinoic acid or a gene product involved in synthesizing or metabolizing retinoic acid; or an agonist or antagonist thereof; or a gene product that is involved in transporting a retinoic acid family member.

Methods of inhibiting mammalian platelet release of CD40 ligand, thromboxanes, or prostaglandin E2, or surface expression of CD40 ligand that involve contacting mammalian platelets with an effective amount of a PPARγ agonist, an RXR agonist, or a combination thereof. As a consequence of inhibiting CD40 ligand and thromboxane release, the present invention allows for inhibition of thrombus fon-nation by (or clotting activities of) activated platelets, as well as treating or preventing CD40 ligand-mediated conditions and / or thromboxane-mediated conditions. Use of PPARγ agonist, RXR agonist, and / or inducers of PPARγ agonist in preparing a stored blood product, and for diagnostic testing of patient samples is also disclosed.

The present invention provides methods of treating proteinuria, and treating renal disorders associated with proteinuria, the methods generally involving administering to an individual having such a disorder an effective amount of retinoic acid receptor agonist or a retinoid X receptor agonist.