68 results about "Aromatic hydrocarbon receptor" patented technology

A class of aromatic hydrocarbon receptor modulator compounds represented by the following formula I, or respective optical isomers, deuterated compounds, prodrugs or pharmaceutically acceptable salts thereof, and a preparation method therefor and the use thereof. The compounds can be used as aromatic hydrocarbon receptor modulators to regulate the activity of aromatic hydrocarbon receptors in vivo, which is of great significance for the treatment of related diseases such as immune diseases, inflammatory diseases, infections, skin diseases, osteoporosis, cancers and neurodegenerative diseases.

The application provides a starch-indole acid derivative and a preparation method and application thereof, and relates to the technical field of modified starches. The starch-indole acid derivative refers to esterified starch generated by esterification reaction of starch, a condensing agent and alkali and indole acid. The starch-indole acid derivative has high resistance and can resist degradation of the stomach and small intestine. After reaching the colon site, the starch-indole acid derivative can be fermented by intestinal flora to release indole acid beneficial to intestinal health. Compared with traditional drug delivery modes such as intragastric administration and intraperitoneal injection, the starch-indole acid derivative has obvious advantages and can significantly increase the content of indole acid in the colon and hepatic portal vein blood. In addition, indole acid can activate an aromatic hydrocarbon receptor to play an immunoregulatory role. The immunoregulatory role of indole acid is superimposed on the regulation role of short-chain fatty acids released by starch fermentation by intestinal flora, so that a product playing an immunoregulatory role through multiple immune system signal pathways is provided.

The present invention relates to pharmaceutical compounds of Formula (I):as further described herein, and pharmaceutical compositions containing such compounds, as well as methods of using these compounds to modulate the activity of aryl hydrocarbon receptor (AhR) and to treat conditions comprising inflammation inside the intestinal tract and certain disorders of the central nervous system affected by the gut-brain axis, including IBD, ulcerative colitis, Crohn's disease, Huntington's disease, and multiple sclerosis.

The invention discloses an application of indoleacetic acid in preparation of a medicine for preventing or treating neuropathic toxicity caused by chemotherapeutics. Experimental results show that the indoleacetic acid (IAA) can significantly relieve pain sensitivity of mice caused by neuropathic toxicity (OIPN) caused by oxaliplatin (OXA), improve morphological damage of dorsal root ganglion (DRG) of the mice and reduce the inflammation level in colon of the mice; however, these benefits are significantly blocked when antagonists are used for the aromatic hydrocarbon receptor (AhR). This indicates that the therapeutic effect of IAA may depend on the activation of the aromatic hydrocarbon receptor (AhR) pathway. The invention provides a new method for treating neuropathic toxicity caused by chemotherapeutics, and expands the application of indoleacetic acid at the same time.

The present invention discloses a novel aporphine compound, its preparation method and applications, and its structural formula is shown as follows. The name of the novel aporphine compound is 2-methoxy-9-hydroxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline (III 11 ). In the present invention: ① By using the computer-aided drug design method in the forefront field of pharmacy, this compound is designed according to the binding requirements of the drug action target; ② This compound is synthesized from 3-methoxyphenethylamine and 2-bromo-5-hydroxybenzaldehyde, and its preparation method is simple; ③ This compound is an aryl hydrocarbon receptor (AhR) agonist and an inducer for the generation of regulatory T cells (Treg cells), and can be used for the prevention and treatment of immune inflammation and related diseases. ④ This compound shows good plasma protein binding rate and bioavailability, and has good prospects for drug development. #imgabs0#

To provide a method for treating a disease. [Solution] The present invention relates to compounds, compositions and methods for modulating skin pigmentation in a subject, and for treating or preventing UV-induced skin damage, erythema, skin aging, sunburn and hyperpigmentation. The compounds, compositions and methods of the present invention generally include compounds derived from Malassezia, including malassezin and indirubin, and / or their chemical analogues. Other uses of the compounds and compositions disclosed herein include, but are not limited to, improvement of hyperpigmentation caused by hyperpigmentation disorders, including melanocyte apoptosis, and modulation of aromatic hydrocarbon receptor (AhR) activity, melanogenesis, melanin production, melanosome biogeneration, melanosome transport, melanocyte activity and melanin concentration.

The invention discloses application of an aromatic hydrocarbon receptor stimulant in preparation of a medicine for treating diarrhea of weaned piglets and / or inhibiting inflammation, and belongs to the field of biological medicine. According to the present invention, with the PAS-B structural domain of the AHR as the target, the virtual screening technology, the target verification test and the weaned piglet diarrhea pharmacodynamic evaluation test are performed to determine the arctigenin as the AHR strong agonist and the anti-inflammatory drug, and the arctigenin has the good treatment effect on the weaned piglet diarrhea. Experimental results show that 10 mg / kg of arctigenin can significantly relieve diarrhea and hemafecia symptoms of weaned piglets, reduce the content of inflammatory factors in serum and intestinal tissues and improve the intestinal structure of weaned piglets, has no significant cytotoxicity, hepatorenal toxicity and intestinal epithelial cell growth inhibition effect, and can be used for preparing a feed additive for weaned piglets. The compound can be used for preparing medicines for treating diarrhea of weaned piglets. The invention provides a new raw material medicine for treating diarrhea of weaned piglets, and has great economic value and wide application prospect.

The technology described herein is directed to modulate the levels of CD8+ T cells in the colon and / or small intestine including administering to a subject in need thereof a therapeutically effective amount of a retinoic acid receptor (RAR) agonist or inhibitor and / or an aryl hydrocarbon receptor (AHR) agonist or inhibitor, and a therapeutic agent.

This invention provides the application of huperzine A in the preparation of drugs for the prevention and / or treatment of pulmonary fibrosis. Using a bleomycin-induced in vitro pulmonary fibrosis model, this invention demonstrates that huperzine A can act as an aryl hydrocarbon receptor agonist, increasing the intracellular expression of aryl hydrocarbon receptors; using a bleomycin-induced mouse pulmonary fibrosis model, this invention demonstrates that huperzine A possesses anti-pulmonary fibrosis pharmacological activity. By studying the in vivo and in vitro bioactivity of huperzine A in the treatment of pulmonary fibrosis, this invention provides new ideas and solutions for the research and development and production of anti-fibrotic drugs.

The invention belongs to the technical field of medicines, and particularly relates to an aromatic hydrocarbon receptor activator as well as a preparation method and application thereof. The aromatic hydrocarbon receptor activator is 6-(3-hydroxyphenyl)-2-methoxyquinoline, and a preparation method of the aromatic hydrocarbon receptor activator comprises the following steps: taking 6-bromo-2-methoxyquinoline, 3-hydroxyphenyl-boric acid, potassium carbonate, tetrakis (triphenylphosphine) palladium and methylbenzene as raw materials, carrying out a condensation reflux reaction under the protection of N2, after the reaction is finished, adding ethyl acetate and water, stirring, and after standing and layering, carrying out suction filtration to obtain the aromatic hydrocarbon receptor activator. An ethyl acetate layer is taken to be prepared into Sabai, and 6-(3-hydroxyphenyl)-2-methoxyquinoline is prepared through elution. It is proved for the first time that 6-(3-hydroxyphenyl)-2-methoxyquinoline can activate the activity of AhR, 6-(3-hydroxyphenyl)-2-methoxyquinoline can serve as an aromatic hydrocarbon receptor activator to be used for preparing the anti-psoriasis medicine, and the 6-(3-hydroxyphenyl)-2-methoxyquinoline has important application value in the aspect of treating diseases caused by abnormal AhR activity.

A hematopoietic stem cell (HSC) proliferation medium includes a basal medium, 0.1 ng / mL to 200.0 ng / mL of thrombopoietin (TPO), 0.1 ng / mL to 200.0 ng / mL of stem cell factor (SCF), 0.1 ng / mL to 20.0 ng / mL of interleukin-3 (IL-3), 0.1 ng / mL to 100.0 ng / mL of interleukin-6 (IL-6), 0.1 ng / mL to 200.0 ng / mL of Flt-3 ligand (FL), 0.1 μg / mL to 20.0 μg / mL of insulin, 0.1 μg / mL to 120.0 μg / mL of transferrin, 0.1 g / L to 3.0 g / L of human serum albumin (HSA), 0.1 μM to 4.0 μM of pyrimido-indole derivative UM729, and 0.1 μM to 2.0 μM of aryl hydrocarbon receptor (AhR) antagonist StemRegenin 1 (SR1). Methods for in vitro proliferation of hematopoietic stem cells (HSCs) and in vitro production of hematopoietic progenitor cells (HPCs) using the HSC proliferation medium are also provided.

The invention discloses a novel aromatic hydrocarbon receptor signaling pathway agonist and application thereof, and belongs to the technical field of medical preparations. The invention aims to provide a cell model for aromatic hydrocarbon receptor signal channel research and is used for aromatic hydrocarbon receptor signal channel research. The invention discloses the effect of aristololactam I in activation of an AhR signal channel for the first time. The prepared renal tubular epithelial cells with activated aromatic hydrocarbon receptor signal channels can be used for preparing cell models for screening candidate drugs for resisting liver and / or kidney diseases by taking AhR as a target spot. In practical application, AhR in renal tubular epithelial cells with activated aromatic hydrocarbon receptor signal channels can be used as a target spot to screen candidate drugs for resisting liver and / or kidney diseases.

The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers, particularly cancers that exhibit elevated expression of FOXA1 and / or FOXA1 gene targets, such as certain breast, liver and / or prostate cancers, including luminal and / or ER-positive forms of breast cancer. Three previously identified adenosine receptor antagonists, CGS-15943, MRS-1220 and SCH-58261, as well as furan ring moiety-possessing derivatives of CGS-15943 are specifically provided for killing cancer cells in a manner that appears to involve activation of the aryl hydrocarbon receptor (AHR) by such compounds. The instant disclosure therefore provides for selecting and / or administering CGS-15943, MRS-1220, SCH-58261 and / or a furan-possessing derivative of CGS-15943, MRS-1220 and / or SCH-58261 as a therapeutic agent to target a cancer cell and / or subject having or at risk of developing a cancer. Methods and compositions for therapies that include such compounds are also provided.

The present invention relates to novel compounds that are effective as modulators of the aryl hydrocarbon receptor (AhR), pharmaceutical compositions comprising the compounds as active ingredients, which are useful for modulating AhR, or preventing or treating diseases, disorders or conditions associated with AhR activity, and therefore, can be used as drugs for preventing or treating diseases, disorders or conditions associated with AhR activity, in particular cancers, cancerous conditions, tumors, fibrotic diseases, conditions of dysregulated immune responses, and the like.

This invention provides an aromatic hydrocarbon receptor agonist with a benzofuran skeleton, its preparation method, and its application, belonging to the field of chemical synthetic drug technology. The compound has the structure shown in Formula I: Formula I. The small molecule compounds of this invention exhibit good agonistic activity against AHR in vitro and show good alleviating effects on psoriasis, inflammatory bowel disease, and atopic dermatitis. Some compounds show better anti-psoriasis effects than currently used clinical drugs.

The application provides an application of Camellia nitidissima endophytic Bacillus thuringiensis in preparation of a medicine for relieving ulcerative colitis, the Camellia nitidissima endophytic Bacillus thuringiensis is preserved in the China General Microbiological Culture Collection Center, and the preservation number is CGMCC No.32945. The Bacillus thuringiensis in the application can treat ulcerative colitis through a multi-target synergistic mechanism of regulating intestinal flora, activating an aromatic hydrocarbon receptor AhR, repairing an intestinal barrier, regulating a metabolic pathway and the like, so as to solve the problems of large side effects and easy recurrence of traditional treatment methods.

The invention belongs to the technical field of biological medicine, and particularly discloses application of an aromatic hydrocarbon receptor as a biomarker in early risk screening of traumatic sepsis. The aromatic hydrocarbon receptor can be used as a new biomarker for predicting the occurrence of the traumatic sepsis, and the expression level of the aromatic hydrocarbon receptor is positively correlated with the occurrence of the post-traumatic sepsis, so that the aromatic hydrocarbon receptor can be used as a screening index for the occurrence risk of the traumatic sepsis. The invention provides a new technical means for early screening of traumatic sepsis.

The present invention discloses a recombinant vector and application method for determining the activity of dioxin-like substances based on the mouse aromatic hydrocarbon receptor, and relates to a genetic engineering. This study mainly selects and intercepts the efficient mouse aromatic hydrocarbon receptor AHR expression sequence through molecular cell biology means, amplifies and subclones it into the pBIND expression vector dedicated to mammalian single hybridization; after successful sequencing verification, the pBIND expression vector and the mammalian single hybridization reporter gene vector pG5luc are co-transfected, and then dioxin-like substances are added to carry out compound activity determination, as well as sensitivity indicators related to the mouse AHR receptor. The present invention is based on the systematic optimization of the mammalian single hybridization reporter gene technology, establishes a toxicological test method, solves the problem of efficient cross-species toxicity assessment, and provides an effective tool for studying the ecotoxicity risk of new dioxin-like pollutants by enhancing the detection sensitivity.

The invention relates to the technical field of medicines, and provides application of albiflorin as an aromatic hydrocarbon receptor agonist. The aromatic hydrocarbon receptor stimulant is albiflorin or a pharmaceutically acceptable salt of the albiflorin. According to the scheme provided by the invention, albiflorin is used as an aromatic hydrocarbon receptor agonist, and can generate an effect of resisting oxidative stress injury of a central nervous system by exciting an aromatic hydrocarbon receptor and regulating a PI3K / AKT / HIF-1 signal channel, so that the central nervous toxicity is improved. The albiflorin serving as the aromatic hydrocarbon receptor agonist can start various signal channels regulated and controlled by an aromatic hydrocarbon receptor, the central nervous toxicity is improved in a targeted manner, and the albiflorin has no cytotoxicity, so that the albiflorin serving as the aromatic hydrocarbon receptor agonist has potential application value in preparation of the medicine for improving the central nervous toxicity.

The application provides a composition for regulating intestinal flora to intervene in rose acne, comprising oral preparations and skin external preparations thereof, and relates to the technical field of biological medicines.The composition is composed of a prebiotic component inulin or a dandelion water extract containing inulin, and a humanized rhamnosus strain or a bacterial body lysate, culture supernatant or metabolite thereof.The composition can promote the proliferation of the humanized rhamnosus in the intestinal tract after being taken orally, significantly enhance the tryptophan metabolism capacity of the humanized rhamnosus, and improve the intestinal indole-3-lactic acid level;ILA enters blood through the intestinal-skin axis, and acts on the skin keratinocyte aromatic receptor, so that the immune homeostasis is systematically regulated and the skin inflammation is relieved.Experiments prove that the composition has a significant prevention and intervention effect on a rose acne model of mice induced by LL-37, can reduce the erythema area, and relieve the inflammatory symptoms.

Small molecule AhR ligands are disclosed. The ligands can induce the differentiation of Tr1 cells to suppress pathogenic immune responses without inducing nonspecific immune suppression. Methods of treatment of autoimmune diseases using the AhR ligands are also disclosed.

To provide novel AHR agonist compounds, pharmaceutical compositions comprising the compounds, and methods of using the compounds to treat specific immune-mediated diseases.SOLUTION: Provided is a compound represented by the following formula, where a ring A is a 5-membered or 6-membered carbocycle; a ring B is a phenyl, or a 5-membered or 6-membered heteroaryl having 1 or 3 heteroatoms, wherein each heteroatom of the heteroaryl is independently selected from N, S, and O; R is H or C1-3 alkyl; X is H, halo, C1-3 alkyl optionally substituted with one or more halo, or a C1-3 alkoxyl; Y is H, C1-4 alkyl, or C3-4 cycloalkyl, wherein the C1-4 alkyl is a primary or secondary alkyl; and Z is CH or N.SELECTED DRAWING: None

To provide novel aryl hydrocarbon receptor (AhR) modulators, useful as a medication for the prevention or treatment of cancer, cancerous condition, tumor, fibrotic disease, or condition with dysregulated immune responses, etc.SOLUTION: The present invention provides an aminopyrimidine derivative, for example, the compound (example 1) of the following formula, or an enantiomer, diastereomer, racemate, solvate, hydrate, or pharmaceutically acceptable salt thereof.SELECTED DRAWING: None

The present disclosure provides compositions for inducing immune tolerance to one or more allergens in a subject. The compositions typically comprise an implantable device, such as an intradermal implantable device, designed to deliver one of more specific antigens (allergens) and aryl hydrocarbon receptor (AhR) agonists. The invention also provides methods for inducing tolerance to a protein or polypeptide antigen (e.g., an allergen) in a subject. The methods involve administering to the subject a pharmaceutical composition that co-presents both the antigen and aryl hydrocarbon receptor (AhR) agonists.

The invention belongs to the technical field of aromatic hydrocarbon receptor ligands, and particularly relates to an AHR ligand 5-methoxy-2-methyl-3-indoleacetic acid and application thereof. According to the invention, a compound 5-methoxy-2-methyl-3-indoleacetic acid (MMIA) is used as an aromatic hydrocarbon receptor (AHR) ligand, and the application of the MMIA in the aspects of enhancing the stability of the AHR, promoting the AHR to enter a cell nucleus, relieving colitis and the like is disclosed. The result of the embodiment shows that the MMIA can be specifically combined and activate the AHR; mMIA gavage treatment can play an anti-inflammatory role and effectively relieve colitis symptoms. AHR is a key molecule for regulating and controlling the steady state of the intestinal tract, can inhibit proinflammatory pathways such as NF-kappa B and the like, reduce secretion of proinflammatory factors such as IL-6 and TNF-alpha, and also can repair damaged mucosa, restore the integrity of the intestinal barrier and improve related symptoms of the colitis from the source.

Small molecule AhR ligands are disclosed. The ligands can induce the differentiation of Tr1 cells to suppress pathogenic immune responses without inducing nonspecific immune suppression. Methods of treatment of autoimmune diseases using the AhR ligands are also disclosed.

Provided herein are compounds (e.g., a compound of Formula (A)) having ARNT degradation activity, and pharmaceutically acceptable derivatives thereof. Also provided are pharmaceutical compositions containing the compounds and methods of using the compounds for treating a subject with an ARNT-mediated disease or disorder.

The present application provides the use of a compound represented by Formula I, a stereoisomer, a pharmaceutically acceptable salt or a prodrug thereof as an aryl hydrocarbon receptor (AHR) modulator. The compound represented by Formula I greatly improves the light stability of the molecular structure compared to the marketed drug benvepidimod, improves the light instability of benvepidimod, and is easily degraded under light. In addition, the activity on the AHR protein is also significantly improved. Finally, the preparation method of the compound represented by Formula I is simple, and can be prepared in kilograms or kilograms, which has a better prospect in subsequent formulation development, safety and clinical application.

The present invention aims to provide an epidermal barrier function improving agent and an aromatic hydrocarbon receptor activator containing Artemisia princeps extract and / or vitamin K as active ingredients. [Solution] The present invention provides an epidermal barrier function improving agent and an aromatic hydrocarbon receptor activator containing Artemisia princeps extract and / or vitamin K as active ingredients.