118 results about "Wnt signaling pathway" patented technology

Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases due to mutations in Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

Conformationally constrained compounds that mimic the secondary structure of reverse-turn regions of biologically active peptides and proteins as well as their prodrugs are disclosed. Such reverse-turn mimetic structures and prodrugs have utility over a wide range of fields, including use as diagnostic and therapeutic agents. Libraries containing the reverse-turn mimetic structures of this invention are also disclosed as well as methods for screening the same to identify biologically active members. The invention also relates to the use of such compounds and prodrugs for inhibiting or treating disorders modulated by Wnt-signaling pathway, such as cancer, especially colorectal cancer, restenosis associated with angioplasty, polycystic kidney disease, aberrant angiogenesis disease, rheumatoid arthritis disease, tuberous sclerosis complex, Alzheimer's disease, excess hair growth or loss, or ulcerative colitis.

Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

Provided are cortical interneurons and other neuronal cells and in vitro methods for producing such cortical interneurons and other neuronal cells by the directed differentiation of stem cells and neuronal progenitor cells. The present disclosure relates to novel methods of in vitro differentiation of stem cells and neural progenitor cells to produce several type neuronal cells and their precursor cells, including cortical interneurons, hypothalamic neurons and pre-optic cholinergic neurons. The present disclose describes the derivation of these cells via inhibiting SMAD and Wnt signaling pathways and activating SHH signaling pathway. The present disclosure relates to the novel discovery that the timing and duration of SHH activation can be harnessed to direct controlled differentiation of neural progenitor cells into either cortical interneurons, hypothalamic neurons or pre-optic cholinergic neurons. The present disclosure also relates to compositions of cortical interneurons, hypothalamic neurons or pre-optic cholinergic neurons, and their precursors, that are highly enriched and can be used in variety of application. These cells can be used therapeutically to treat neurodegenerative and neuropsychiatric disorders, and can be used for disease modeling and drug screening.

The invention provides a method for producing a retinal tissue by (1) subjecting pluripotent stem cells to floating culture in a serum-free medium containing a substance inhibiting the Wnt signal pathway to form an aggregate of pluripotent stem cells, (2) subjecting the aggregate to floating culture in a serum-free medium containing a basement membrane preparation, and then (3) subjecting the aggregate to floating culture in a serum-containing medium. The invention also provides a method for producing an optic-cup-like structure, a method for producing a retinal pigment epithelium, and a method for producing a retinal layer-specific neural cell.

The invention relates to heterocyclic compounds with Wnt signal channel inhibition activity, particularly including compounds, pharmaceutically acceptable salts, various isotopes, various isomers or various crystal structures thereof having a structure represented by a general formula I (shown in the specification). By the compounds and a composition of the compounds, a Wnt signal channel can be effectively inhibited and diseases related to the Wnt signal channel can be treated or prevented.

Methods and compositions for modulating growth of a neuron with a Wnt, a Wnt-like substance, and/or a chemical compound affecting a Wnt signaling pathway are disclosed. Also disclosed are methods for identifying a substance that modulates growth of a neuron by obtaining a candidate substance and contacting the candidate substance with the neuron are disclosed and methods for modulating growth of a neuron in a subject using a Wnt, a Wnt-like substance, and/or a chemical compound affecting a Wnt signaling pathway. The Wnt, Wnt-like substance, and/or chemical compounds affecting a Wnt signaling pathway can be delivered to the subject using gene therapy techniques. Also disclosed are pharmaceutical compositions for modulating growth of a neuron in a mammal that include a Wnt or a Wnt-like substance. Methods and compositions for inhibiting growth of a neuron are also disclosed.

The invention provides a method for producing a cell aggregate containing a ciliary marginal zone-like structure by culturing a cell aggregate containing a retinal tissue in which Chx10 positive cells are present in a proportion of 20% or more of the tissue in a serum-free medium or serum-containing medium, each containing a substance acting on the Wnt signal pathway for only a period before the appearance of a RPE65 gene expressing cell, followed by culturing the “cell aggregate in which a RPE65 gene expressing cell does not appear” thus obtained in a serum-free medium or serum-containing medium, each not containing a substance acting on the Wnt signal pathway and so on.

Provided is an efficient method of inducing differentiation of a pulp cell into an odontoblast. Also provided is an agent for inducing differentiation capable of inducing differentiation into an odontoblast efficiently. The method of inducing differentiation of a pulp cell into an odontoblast includes using a substance capable of activating a Wnt signaling pathway. Further, the agent for inducing differentiation includes a substance capable of activating a Wnt signaling pathway. Specifically, the substance capable of activating a Wnt signaling pathway is any one selected from sodium perchlorate, sodium perchlorate, lithium chloride, Norrin, and R-Spondin2.

The invention belongs to the technical field of medicines, and particularly relates to a myocardial small molecular compound for idiosyncratically promoting proliferation of myocardial cells and application thereof. The myocardial small molecular compound total comprises a type A, a type B and a type C which have a common core structure, namely (3 (1, 2, 4) triazole (3, 4-b) (1, 3, 4) bismuththiol). The myocardial small molecular compound is obtained from a small molecular compound library by means of model organism zebra fish screening, so as to be capable of idiosyncratically promoting proliferation of myocardial cells inside zebra fish bodies. Importantly, the myocardial small molecular compound is capable of inducing embryonic stem cells of a small mouse to differentiate and proliferate towards the myocardial cells. As proved, the myocardial small molecular compounds are antagonists to inhibit wnt signaling pathways. The myocardial small molecular compound can be used as pilot drugs for treating heart diseases and further is used for optimizing and evaluating candidate drug targets thereof.

The invention relates to a method for inducing a human pluripotent stem cell to differentiate into an RPE cell. According to the method, an inhibitor is used for inducing the human pluripotent stem cell to differentiate into a neural precursor; after Shh, IGF1 and EGF growth factors are utilized to activate ERK 1/2, JNK, Sonic hedgehog signal routes, the cell is presented as the shape of neuroepithelium, Activen A and Chir99021 are added to activate TGFbeta and Wnt signal routes respectively to induce a neuro-epithelial cell into a retinal progenitor cell; adherent culture is conducted on theretinal progenitor cell to obtain an RPE cell at an underdeveloped state. The invention further studies the field of applying the underdeveloped RPE cell to treating retinal degenerative diseases. Compared with the prior art, the method firstly makes three stages of differentiating the human pluripotent stem cell to the underdeveloped RPE cell and related small molecular substances and growth factors used therein clear. Compared with a matured RPE, the underdeveloped RPE obtained through differentiation can treat the retinal degenerative diseases more effectively after being transplanted.

The invention discloses a method for preparing and separating definitive endoderm (DE); the invention also discloses a differential medium used for promoting cytotropism differentiation of DE; the differential medium contains activin A and Wnt signal channel agonist; and the invention also discloses a surface marker used for sorting endoderm.

The invention discloses application of sulindac in preparation of a medicine for treating autism. The application of sulindac in preparation of the medicine for treating autism is characterized in that a VPA (Valproic Acid) autism animal model shows that sulindac is able to reduce abnormal behavior of an autistic, such as repeated mechanical behavior deficiency and human communication disorders; the primary culture neuron and VPA autism animal model verify the occurrence mechanism of autism as well as the functional mechanism of sulindac in treating autistic, and also prove that sulindac has oxidation resistance, and the oxidation resistance is related to down-regulating of the activity of a canonical Wnt signal channel. Therefore, sulindac is able to reduce the repeated mechanical behavior, abnormal behavior and human communication disorders of the autistic and can be used for preparing the medicine for treating autism.

The invention provides a preparation method of epicardial cells from multipotent stem cells. The method comprises the following steps: (1) by activating WNT signal pathways, inducing the multipotent stem cells to be differentiated into mesodermal cells; 2) by inhibiting the WNT signal pathways, converting the mesodermal cells obtained in the step 1) into myocardial precursor cells; 3) by activating retinoic acid signal pathways and the WNT signal pathways, converting the myocardial precursor cells obtained in the step 2) into anterior epicardial cells; and 4) preparing the epicardial cells from the anterior epicardial cells obtained in the step 3). The invention further relates to a method for preparing vascular smooth muscle cells and cardiac fibroblasts from the multipotent stem cells, the epicardial cells, the vascular smooth muscle cells and the cardiac fibroblasts prepared with the method, and application of the epicardial cells, the vascular smooth muscle cells and the cardiac fibroblasts.

The invention relates to the technical field of organoid culture, in particular to a culture medium for preserving organoids at room temperature and a method for maintaining the growth activity of the organoids. The culture medium for preserving the organoids at room temperature comprises a DMEM high-glucose culture medium, Glutamax, HEPES, antibiotics, Matrigel, additives, a TGF-beta inhibitor and a Wnt signal pathway activator, and the volume fraction of the Matrigel is 20%-25% in the culture medium for preserving the organoids at room temperature. The culture medium provided by the invention can improve the biological activity of organoid preservation, and the method for maintaining the growth activity of the organoids can ensure that the organoids can maintain the activity for the longest time at room temperature, the growth activity and morphology of the organoids are not influenced, the activity can be quickly recovered after the organoids are transferred into a cell incubator, the growth of the organoids is continued, and the dissociation phenomenon is avoided.

The invention provides compound used as a Wnt signal pathway activator, and a preparation and an application thereof. The compound is a compound of formula (I) or formula (II). The compound can be used for preparing medicines for adjusting a classic Wnt signal pathway, and can also be used for researching the classic Wnt signal pathway. The compound also provides a new idea for screening the medicines for adjusting the Wnt signal pathway and medicines for preventing and treating classic Wnt signal pathway related diseases, and researching the application of the Wnt signal pathway in stem cells.

The invention provides applications of bruceine D in preparing a Wnt/Notch signal channel inhibitor preventing/treating drug. The Wnt/Notch signal channel inhibitor preventing/treating drug is a drug composition which is prepared by taking bruceine D as an active ingredient, and is prepared from bruceine D and a pharmaceutic adjuvant, and can be prepared into oral preparations, injection preparations, or transdermal drugs. A human liver cancer tumor cell line model and a human normal liver cell line model are used for evaluating in vitro antitumor effect of bruceine D, a zebra fish model is used for evaluating inhibition effect of bruceine D on Wnt/Notch signal channel, and it is confirmed by experiment results that body axis dysplasia caused by inhibition of Wnt signal channel is observed when death of zebra fish is not caused by 100<mu>M of bruceine D. Influences of bruceine D on Wnt-Notch signal channel key proteins are disclosed by in vitro and vivo antitumor activity experiments of bruceine D for the first time, the important effect of Wnt-Notch signal channel on liver cancer, and the inner relationship of Wnt-Notch signal channel are confirmed, novel applications of bruceine D in preparing the drugs used for preventing/treating liver cancer are provided, the drugs used for preventing/treating liver cancer are provided for clinical therapy, and high application value is achieved.

The invention provides means and methods for inhibiting growth of a cancer. The means in some embodiments comprise proteins and antibodies that binds an extracellular part of a membrane associated member of the epidermal growth factor (EGF) receptor family and an extracellular part of a membrane associated member of a WNT signaling pathway. Further provided are various cells and assays that are helpful in the production of the proteins, antibodies and cells.

The invention discloses a DLD1 stable cell strain efficiently expressing human PKM1 protein and a construction method thereof, and belongs to the field of animal cell strains. The construction method comprises the following steps of: constructing a recombined human PKM1 gene lentiviral expression vector; packaging and harvesting lentivirus; transfecting DLD1 cell; and obtaining the stable cell strain through puromycin screening, RT-PCR and Western Blot technological detection. The stable cell strain constructed according to the method provides a powerful tool for searching colon cancer Wnt signal path and tumor energy metabolism.