44 results about "Wnt inhibitor" patented technology

Described herein are methods of treating a disorder or disease in which aberrant Wnt signaling is implicated, with a variety of compounds, including Wnt inhibitor compounds. More particularly, it 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.

Compositions and methods for the treatment of bone diseases, bone fractures, bone injuries and other bone abnormalities involving the use of Dkk protein, a Wnt antagonist, a Wnt inhibitor, or any other related protein for the stimulation or enhancement of mineralization and for stimulating the renewal of cells. One Dkk protein, Dickkopf-2 (Dkk-2), acts to stimulate bone formation independently of Wnt proteins which may be inhibited and / or antagonized by Dkk-2. Dkk-2 displayed enhanced specific targeting ability and enhanced biological activity in stimulating or enhancing mineralization. Dkk-2 also played a role in the differentiation and self-renewal of hematopoietic stem cells and mesenchymal stem cells, particularly in osteoblastogenesis and osteoclastogenesis.

Methods and compositions are provided for the protection of normal cells from cytoreductive therapy that target proliferating cells, by administering an inhibitor of Wnt signaling pathways. Wnt signaling is critically important for homeostasis of the epithelial lining of the adult intestine and other proliferating normal adult tissues.

A population of enteroendocrine cells (EEC) is obtained from a mammalian post-natal cell population, such as a population including post-natal stem cells, by treating the population with a plurality of small molecules that upregulate ChgA and promote differentiation of the cells to form the enteroendocrine cells. The upregulation of ChgA is such that the fraction of cells expressing CGA in the obtained cell population, as measured by a ChgA Immunostaining Assay, is at least about 1.5%. Small molecules that can be used to differentiate the post-natal cells into the enteroendocrine cells can include at least one of a Wnt activator, a Notch inhibitor, a Wnt inhibitor, a MEK / ERK inhibitor, a growth factor, a HDAC inhibitor, a Histone Methylation Inhibitor, a Tgf-β inhibitor, and a NeuroD1 activator. Also, the insulin expression of a population of mammalian cells is increased by treating the population with a plurality of small molecules that increase the insulin expression.

Methods and compositions are provided for the protection of normal cells from cytoreductive therapy that target proliferating cells, by administering an inhibitor of Wnt signaling pathways. Wnt signaling is critically important for homeostasis of the epithelial lining of the adult intestine and other proliferating normal adult tissues.

The invention provides methods of inhibiting hair growth in a post-natal subject by contacting a matured hair follicle cell with a DKK polypeptide. The inhibitory mechanism induced by a DKK polypeptide results in a reversible, transient inhibition of hair growth.

A method for generating chondrocytes and / or cartilage, optionally articular like non-hypertrophic chondrocyte cells and / or cartilage like tissue and / or hypertrophic chondrocyte like cells and / or cartilage like tissue, the method comprising: a. culturing a primitive streak-like mesoderm population, optionally a CD56+, PDGFR[alpha]+KDR- primitive streak-like mesoderm population, with a paraxial mesoderm specifying cocktail comprising: i. a FGF agonist; ii. a BMP inhibitor; optionally Noggin, LDN-193189, Dorsomorphin; and iii. optionally one or more of a TGF[beta] inhibitor, optionally SB431524; and a Wnt inhibitor, optionally DKK1, IWP2, or XAV939; to specify a paraxial mesoderm population expressing cell surface CD73, CD105 and / or PDGFR-beta; b. generating a chondrocyte precursor population comprising: i. culturing the paraxial mesoderm population expressing CD73, CD105 and / or PDGFR-beta at a high cell density optionally in serum free or serum containing media; ii. culturing the high cell density CD73+, CD105+ and / or PDGFR[beta]+ paraxial mesoderm population with a TGF[beta]3 agonist in serum free media to produce a high cell density Sox9+, collagen 2+ chondrocyte precursor population; and c. either i. culturing the high cell density Sox9+, collagen 2+ chondrocyte precursor population with the TGFbeta3 agonist for an extended period of time to produce an articular like non-hypertrophic chondrocyte cells and / or cartilage like tissue; or ii. culturing the high cell density Sox9+ collagen2+ chondrocyte precursor population with a BMP4 agonist for an extended period of time to produce a hypertrophic chondrocyte like cells and / or cartilage like tissue.

The present invention relates to endogenous cardiac stem-progenitor cells (eCSCs). Provided herein are c-kitpos CD166pos eCSCs that are negative for the hematopoietic marker, CD45 and the mast cell marker, Tryptase. These single cell derived eCSCs can differentiate into a variety of specific cell types corresponding to the derivatives of the three germ layers. Also provided herein is a stage-specific TGF-P-Family / Wnt-Inhibitor cocktail for modulating in vitro myogenic specification and maturation of c-kitpos eCSCs. Also provided herein are methods of modulating eCSCs clonal expansion and differentiation. Also provided herein are screening assays for small organic molecules that modulate early cardiomyogenic progenitor cells. The invention further relates to the use of these modulated cells in prophylactic and therapeutic methods, including in pharmaceutical compositions of such cells, growth factors and / or small organic compounds. Finally, the invention relates to the use of such differentiated cells in transplantation and medical treatments.

Compositions and methods for the treatment of bone diseases, bone fractures, bone injuries and other bone abnormalities involving the use of Dkk protein, a Wnt antagonist, a Wnt inhibitor, or any other related protein for the stimulation or enhancement of mineralization and for stimulating the renewal of cells. One Dkk protein, Dickkopf-2 (Dkk-2), acts to stimulate bone formation independently of Wnt proteins which may be inhibited and / or antagonized by Dkk-2. Dkk-2 displayed enhanced specific targeting ability and enhanced biological activity in stimulating or enhancing mineralization. Dkk-2 also played a role in the differentiation and self-renewal of hematopoietic stem cells and mesenchymal stem cells, particularly in osteoblastogenesis and osteoclastogenesis.

The invention relates to the technical field of biological medicines, in particular to application of a Wnt inhibitor Wnt-C59 in preparation of a medicine for treating dilated cardiomyopathy caused bySCN5A mutation. According to the invention, SCN5A genotype detection is used as an entry point for the first time, and a Wnt pathway specific inhibitor Wnt-C59 is used for inhibiting abnormal activation of a Wnt / beta-Catenin pathway caused by SCN5A gene mutation, so that the prognosis of the cardiac function of an expanded cardiomyopathy patient with SCN5A gene mutation is improved. According tothe experiment, the treatment effect of Wnt-C59 on the dilated heart disease is detected by constructing an aging and adriamycin induced dilated heart disease model, changing the cardiac function, activating related signal molecules and other indexes, and a theoretical basis is provided for application of Wnt-C59 to clinical treatment of dilated cardiomyopathy. The invention provides a new treatment method for the dilated cardiomyopathy caused by SCN5A mutation, brings dawn to the patients, and has a good application prospect.

A population of enteroendocrine cells (EEC) is obtained from a mammalian post-natal cell population, such as a population including post-natal stem cells, by treating the population with a plurality of small molecules that upregulate ChgA and promote differentiation of the cells to form the enteroendocrine cells. The upregulation of ChgA is such that the fraction of cells expressing CGA in the obtained cell population, as measured by a ChgA Immunostaining Assay, is at least about 1.5%. Small molecules that can be used to differentiate the post-natal cells into the enteroendocrine cells can include at least one of a Wnt activator, a Notch inhibitor, a Wnt inhibitor, a MEK / ERK inhibitor, a growth factor, a HDAC inhibitor, a Histone Methylation Inhibitor, a Tgf-β inhibitor, and a NeuroD1 activator. Also, the insulin expression of a population of mammalian cells is increased by treating the population with a plurality of small molecules that increase the insulin expression.

The present disclosure provides compounds that may be useful for inhibiting Wnt pathway comprising compounds of the formula: (Ia) or (Ib) wherein the variables are as defined herein. In some aspects, the compounds may be used to inhibit the Wnt pathway and used to treat cancer, myocardial infarction, osteopetrosis, or used in the maturation of a precursor cell to a mature cell. Also provided herein in are pharmaceutical compositions of the compounds described herein.

The present invention relates to therapeutic combinations comprising WNT inhibitors and methods for treating cancers using combination therapy.

The invention discloses an application of a Wnt inhibitor ICG001 in the preparation of medicines for treating hematopoietic aregenerative diseases. The Wnt inhibitor ICG001 can inhibit a CBP mediated Wnt signal path in order to inhibit depletion of too high Wnt signal hematopoietic stem cells, induced by SIRT6 deletion. The invention discloses the application of the Wnt inhibitor ICG001 in the preparation of the medicines for treating hematopoietic aregenerative diseases, and an action mechanism of the ICG001 in promotion of regeneration of SIRT6 knockout hematopoietic stem cells.

The invention discloses an application of a Wnt inhibitor ICG001 in the preparation of medicines for treating hematopoietic aregenerative diseases. The Wnt inhibitor ICG001 can inhibit a CBP mediated Wnt signal path in order to inhibit depletion of too high Wnt signal hematopoietic stem cells, induced by SIRT6 deletion. The invention discloses the application of the Wnt inhibitor ICG001 in the preparation of the medicines for treating hematopoietic aregenerative diseases, and an action mechanism of the ICG001 in promotion of regeneration of SIRT6 knockout hematopoietic stem cells.

The invention provides methods of monitoring differential gene expression of biomarkers to determine patient sensitivity to Wnt inhibitor, methods of determining the sensitivity of a cell to an Wnt inhibitor by measuring biomarkers, methods of screening for candidate Wnt inhibitor, Wnt inhibitor for use in head and neck squamous cell carcinoma.

The present invention relates to combined therapy of cancer using an epithelial cell adhesion molecule (EpCAM) inhibitor and a Wnt signaling inhibitor. Specifically, the EpCAM inhibitor is an antibody which is directed to an extracellular domain (EpEX) of EpCAM. The combined therapy is effective in inducing apoptosis of cancer cells, inhibiting cancer sternness properties, tumor progression and / or metastasis, and / or prolonging survival of a cancer patient.

The present invention provides methods comprising combination therapy for treating cancer. Wnt pathway inhibitors in combination with mitotic inhibitors administered in a staggered or sequential dosing manner for the treatment of cancer and other diseases.

Provided are methods for improving the proliferation and sternness of limbal stem cells (LSCs) by adding a Wnt inhibitor to a medium for limbal explant cultures.When human limbal explants are cultured according to the methods, the Wnt / β-catenin signaling is inhibited, resulting in improvement of LSC proliferation, and improvement in the sternness of LSCs, and thus the LSCs may be obtained in high yield. These effects may lead to a higher success rate of transplantation of a limbal explant outgrowth sheet into a LSCD patient.

To provide a method for producing induced pluripotent stem cells (iPS cells) that can initialize somatic cells without using feeder cells or a substrate. For production of iPS cells, the following steps are carried out: I. introducing an initialization gene into a somatic cell; and II. performing initialization and amplification culture of the cell into which the gene has been introduced, in a liquid medium comprising at least one of a protein kinase Cβ (PKCβ) inhibitor and a WNT inhibitor under a suspension culture condition.

Provided herein are methods of generating Gata6-positive brown adipose progenitor cells, and brown adipose cells and tissue therefrom. Additionally, provided herein are methods of generating UCP1 positive organoids. Generally, the methods include a step of culturing brown adipose progenitor cells in a medium containing an FGF signaling pathway activator, a BMP signaling pathway activator, a TGFβ activator, a Wnt inhibitor, and a thyroid hormone receptor activator.

The invention provides methods of monitoring differential gene expression of biomarkers to determine patient sensitivity to Wnt inhibitor, methods of determining the sensitivity of a cell to an Wnt inhibitor by measuring biomarkers, methods of screening for candidate Wnt inhibitor, Wnt inhibitor for use in head and neck squamous cell carcinoma.

Isoquinoline compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an isoquinoline compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases, 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 is a method for producing renal collecting duct principal cells, including culturing ureteric bud cells or cells that have been differentiated from ureteric bud cells in a medium comprising a TGFβ inhibitor, a Wnt inhibitor, and a phosphodiesterase inhibitor. Also, provided is a method for producing a renal collecting duct principal cell-containing organoid, including culturing a ureteric bud organoid or an organoid that has been differentiated from a ureteric bud organoid in a medium comprising a TGFβ inhibitor, a Wnt inhibitor, and a phosphodiesterase inhibitor.

The invention relates to the technical field of biomedicine, in particular to the application of Wnt inhibitor Wnt-C59 in the preparation of medicines for treating dilated cardiomyopathy caused by SCN5A mutation. The present invention proposes for the first time that SCN5A genotype detection is used as an entry point, and the Wnt pathway-specific inhibitor Wnt-C59 is used to inhibit the abnormal activation of the Wnt / β-Catenin pathway caused by the SCN5A gene mutation, so as to improve the dilated cardiomyopathy caused by the SCN5A gene mutation Patient cardiac function prognosis. The experiment established a model of heart dilation induced by aging combined with doxorubicin, and detected the therapeutic effect of Wnt‑C59 on heart dilation by changes in cardiac function and activation of related signaling molecules, so as to provide a theory for the clinical application of Wnt‑C59 in the treatment of dilated cardiomyopathy in accordance with. The invention provides a new treatment method for SCN5A mutation-induced dilated cardiomyopathy, brings dawn to this type of patients, and has a good application prospect.

A culture medium comprising a WNT inhibitor, a SRC inhibitor and a protein kinase C (PKC) inhibitor is disclosed. The medium is devoid of an amount of GSK3beta inhibitor that increases beta-catenin translocation to the nucleus of a pluripotent stem cell being cultured in the culture medium. Uses thereof are also disclosed.

Disclosed herein are methods of deriving, producing, maintaining, or expanding embryonic stem cells (ESCs) from avian species and a culture medium used for such methods. According to various embodiments, the method includes culturing an embryo extracted from an avian egg in a culture medium to harvest cells from yolk of the avian egg; dissociating cells from the cultured embryo; isolating a morphologically undifferentiated ESC colony from the dissociated cells in a culture medium; and culturing the isolated ESC colony in the presence of ovotransferrin, thereby deriving ESCs. According to various embodiments, the culture medium includes a Wnt inhibitor; a protein kinase C (PKC) inhibitor; ovotransferrin; an inhibitor of activin receptor-like kinases-4, -5, and -7; and a leukemia inhibitory factor (LIF).

Enhanced methods for the generation of medial ganglionic eminence (MGE) cells from pluripotent stem cells are provided that involve an additional step of contacting the cells with an activator of FGF8 signaling while differentiating Pax6+ cells progenitor cells into MGE cells with an activator of sonic hedgehog, and optionally a Wnt inhibitor. The activator of FGF8 signaling shifts the differentiation of the population of cells to NKX2.1+ MGE cells, rather than to CopuTFII+ caudal ganglionic eminence (CGE) cells. Methods for treatment of neurological disorders, such as epilepsy, by transplant of MGE cells, or GABAergic interneurons derived from human pluripotent stem cells, into a subject in need of treatment are also provided. Human pluripotent stem cell derived MGE cells when transplanted successfully suppress spontaneous seizures, e.g. in epilepsy. We also have developed a method to purify MGE cells and maturing interneurons from differentiated pluripotent stem cells using cell surface marker and molecular beacon technology.

The invention relates to a method for promoting maturation of myocardial cells differentiated from multipotential stem cells. In the 0-1 day, the multipotential stem cells which are subcultured to bethe 4-5 generation are subjected to induced differentiation, and a culture medium used in the method contains a GSK-3 inhibitor with the concentration being 2-15 mu M / L; in the 2-3 day, the culture medium is used for conducting induced differentiation continuously; in the 4-5 day, a culture medium containing a Wnt inhibitor with the concentration being 2-10 mu M / L is used for conducting induced differentiation; in the 14-20 days, a culture medium containing retinoic acid with the concentration being 0.2-5 mu M / L is used for conducting induced differentiation continuously, later on, the culturemedium is used for conducting induced differentiation culture on the multipotential stem cells, wherein in the 1-6 days, a first induced differentiation culture medium is used and comprises an RPMI-1640 basic culture medium and B27-insulin, after the 7 day, a second induced differentiation culture medium is used and comprises the RPMI-1640 basic culture medium and B27, or in the whole induced differentiation culture process, a CDM3 induced differentiation culture medium or a serum-free induced differentiation culture medium is used, and the CDM3 induced differentiation culture medium comprises the RPMI-1640 basic culture medium, serum albumin, ascorbic acid and double-antibody.