10 results about "Hedgehog signaling pathway" patented technology

Disclosed herein are analogues of itraconazole that are potent hedgehog signaling pathway inhibitors. The compounds are expected to be useful in the treatment of cell proliferation disorders such as cancer, particularly cancers that are dependent upon the hedgehog signaling pathway such as basal cell carcinoma and medulloblastoma.

The invention relates to a biomarker combination for treating SHH subtype medulloblastoma, and aims to solve the problems that existing treatment targets are deficient, the curative effect is limited and precise treatment is insufficient. The invention reveals that an m6A-YTHDF2 signal axis is a novel treatment target of SHH-MB for the first time, the YTHDF2 regulates and controls the expression of a downstream target gene DENND2A through an m6A dependency mode, the high expression of the YTHDF2 is related to poor prognosis of a patient, and knock-down of the YTHDF2 can significantly inhibit the proliferation and balling ability of SHH-MB cells. According to the invention, the TET-ON regulated SHH-MB cell line capable of inducing to knock down YTHDF2 is constructed, and a tool is provided for drug screening; it is clear that a YTHDF2 inhibitor (such as DC-Y13-27 and the like) can achieve the anti-tumor effect by down-regulating DENND2A expression, and the drug sensitivity of SHH-MB tumor cells to a Hedgehog signal channel small molecule inhibitor Vismodegib (GDC-0449) is improved.

Micelle compositions comprising a hedgehog pathway inhibitor and their use in treating skin diseases, conditions, or disorders, such as skin cancers, including basal cell carcinoma, are disclosed.

The present application relates to the application of imperatorin in the preparation of a drug for inhibiting the Hedgehog signal pathway, and discloses that imperatorin can inhibit the Hedgehog signal pathway activated by Shh, inhibit the Hedgehog signal pathway activity activated by SMO overexpression, and inhibit the Hedgehog signal pathway activity activated by SMO drug-resistant mutation, and can obviously inhibit the growth of tumors in vivo caused by abnormal activation of the Hedgehog, and in particular, it is disclosed that imperatorin can inhibit the Hedgehog signal pathway activity activated by SMO drug-resistant mutation, which provides a new strategy for treating tumors caused by abnormal activation of the Hedgehog, and expands the application field of imperatorin.

The invention discloses application of lycopene in preparation of medicines for treating hidden testis, and belongs to the technical field of biological medicines. As a naturally existing carotenoid, the lycopene can effectively improve spermatogenesis of a mouse suffering from cryptorrhea, and the research result provides a solid foundation for treatment of a patient suffering from cryptorrhea by the lycopene; the lycopene regulates and controls the spermatogenesis of the hidden testis through a hedgehog signal channel by reducing the level of active oxygen in tissues. The invention verifies the effects of lycopene on the aspects of reproductive system, influence on spermatogenesis, sperm motility protection and the like, and aims to verify factors influencing spermatogenesis and the action mechanism of lycopene on spermatogenesis of mammals. And a reliable theoretical basis is provided for the application of the gene in the aspects of excellent breeding of large animals, even male infertility and the like of human beings.

The present application relates to a kind of novel Hedgehog signal pathway inhibitor and preparation method thereof, the Hedgehog signal pathway inhibitor has the structure shown in formula (I).The Hedgehog signal pathway inhibitor of the present application can effectively inhibit SMO receptor activity, and block SHH signal pathway. With good effect of blocking the seizure caused by excessive or super-synchronous neuron discharge in brain. As epilepsy treatment candidate drug has good application prospect.

The application provides application of chamaecyparis funebris polysaccharide in preparation of a medicine for preventing and / or treating pulmonary fibrosis, and belongs to the technical field of medicines.The application finds that chamaecyparis funebris polysaccharide can effectively prevent and / or treat pulmonary fibrosis, and can effectively reduce lung injury and inhibit lung inflammation; chamaecyparis funebris polysaccharide inhibits fibrosis and migration of human embryo lung fibroblasts induced by recombinant human transforming growth factor, improves lung function injury and pulmonary fibrosis of a bleomycin-induced pulmonary fibrosis mouse, inhibits inflammatory cell infiltration of bronchial alveoli and expression of NOD-like receptor family pyridine domain-containing protein 3 (NLRP3) in lung tissue of the pulmonary fibrosis mouse, and further inhibits lung inflammation; chamaecyparis funebris polysaccharide can also inhibit the Hedgehog signal pathway in vitro and in vivo, and the improvement of lung function of the bleomycin-induced pulmonary fibrosis mouse and the treatment of pulmonary fibrosis by chamaecyparis funebris polysaccharide are further enhanced when assisted by a Hedgehog pathway inhibitor.

The application provides a culture medium for inducing human umbilical cord mesenchymal stem cells to differentiate into pancreatic beta-like cells and an application thereof. The culture medium comprises culture medium A, culture medium B and culture medium C; the culture medium A contains Activin A, Wnt3a, FBS and sodium butyrate, the culture medium B contains retinoic acid, a hedgehog signal pathway inhibitor, a cell growth factor and FBS, and the culture medium C contains nicotinamide, a GLP-1 receptor agonist, betacellulin, HGF, an ALK5 inhibitor, a gamma-secretase inhibitor and FBS. The culture medium provided by the application can efficiently induce human umbilical cord mesenchymal stem cells to differentiate into mature, functional and antigen-free pancreatic beta-like cells through three stages, and overcomes the defects of low differentiation efficiency and immature cell function in the process of inducing human umbilical cord mesenchymal stem cells to differentiate into pancreatic beta-like cells in the prior art.

The invention provides a salt form and a crystal form of a chiral heterocyclic compound with hedgehog pathway antagonist activity. The compound is (R)-1-(6-(5 '-chloro-3, 5-dimethyl-[2, 4'-bipyridyl]-2 '-yl)-5-methyl-5, 6, 7, 8-tetrahydropyrido [4, 3-d] pyrimidine-2-yl) piperidine-4-alcohol, the pharmaceutically acceptable salt of the compound has a high-temperature endothermic peak, so that the compound has good thermal stability, and the crystal form is basically not changed when the compound is heated. Particularly, the fumarate anhydrous crystal form F shows optimal thermodynamic stability, good physical and chemical stability and myeloblastoma resistance, better hygroscopicity, solubility and bioavailability compared with a free alkali amorphous form, better pharmacokinetic characteristics compared with GDC-0449, a better tumor inhibition effect and higher hedgehog signal channel inhibition activity.