27 results about "Prolyl Hydroxylases" patented technology

The invention relates to an expression cassette and a method for producing humanized triple helix collagen by using the expression cassette, and belongs to the technical field of genetic engineering. The expression cassette sequentially comprises a promoter sequence, a fusion gene and a terminator sequence from upstream to downstream, the fusion gene comprises nucleotide fragments A, B and C, each fragment comprises an immutable region and a variable region, and the variable region is selected from I, II, III, IV and XVII type human collagen. A kex2 protease recognition site KR is introduced into an expression box, so that an expression product can be subjected to trisection cutting, and three equal-length peptide chains with a triple-helix basic structure are formed. The invention also provides a recombinant humanized collagen with a self-assembled triple helix structure and a production method thereof, and the method comprises the following steps: preparing a recombinant expression vector containing the expression cassette and a proline hydroxylase expression vector, and transferring the two expression vectors into competent cells for co-expression. The method can be used for producing the recombinant humanized collagen with the self-assembled triple-helix structure, and has a good application prospect.

A method for treating inflammatory bowel disease using prolyl hydroxylase domain-containing protein (PHD) inhibitors and additional agents is described herein.

Described herein are methods of inflammatory bowel disease using a Prolyl Hydroxylase Domain-Containing Protein (PHD) inhibitor and an additional agent.

Disclosed herein is a method of modifying a T cell during T cell activation comprising contacting the T cell with an inhibitor of prolyl hydroxylase. Also disclosed is a method of producing a chimeric antigen receptor (CAR) or T cell receptor (TCR) T cell comprising (i) modifying the T cell during activation of the T cell by contacting the T cell with an inhibitor of prolyl hydroxylase, (i) introducing a CAR or TCR transgene into the modified T cell, and (iii) harvesting the CAR or TCR T cell. In particular, the inhibitor of prolyl hydroxylase is a small molecule prolyl hydroxylase inhibitor, such as 1, 4-DPCA. The harvested CAR or TCR T cells can be used for adoptive T cell immunotherapy of cancer.

To provide dosing regimens for administering a HIF prolyl hydroxylase inhibitor in the treatment or prevention of anemia, such as anemia secondary to or associated with chronic kidney disease, or anemia associated with or resulting from chemotherapy.SOLUTION: A pharmaceutical composition in a form of a tablet or capsule comprising Compound 1 having the following structure, for use in a method of increasing hemoglobin levels in a patient in need thereof relative to a baseline hemoglobin level, wherein the patient has a hemoglobin level of ≤10.5 g / dL or ≥9.5 g / dL and ≤12 g / dL at a start of treatment, a serum hemoglobin level increases by at least about 0.1 to about 1.0 g / dL relative to the baseline hemoglobin level, and the pharmaceutical composition is used such that Compound 1 is administered to the patient once daily, for example at a dose of about 150 mg.SELECTED DRAWING: Figure 1a

The present invention provides a thyroid hormone receptor β (TRβ) agonist compound, a preparation method and an application thereof. The compound and the pharmaceutically acceptable salts, esters, amides or carbamates, as well as isomers, racemates, prodrugs, co-crystallized complexes or solvates of the compound can be used as thyroid hormone receptor β agonists, and the prepared thyroid hormone receptor β agonist has a good activation effect on wild-type and mutant thyroid hormone receptor β, has a weak effect or basically no effect on thyroid hormone receptor α (TRα) and prolyl hydroxylase (PHD2) targets, and has good selectivity. Therefore, the compound can be used in the prevention or treatment of thyroid hormone receptor β-mediated related diseases.

The invention discloses a novel prolyl hydroxylase 2 and histone deacetylase 6 dual selective inhibitor as shown in a formula I as well as a preparation method and application thereof, and the prolyl hydroxylase 2 and histone deacetylase 6 dual selective inhibitor plays a role in relieving acute kidney injury caused by cis-platinum by simultaneously inhibiting the activity of prolyl hydroxylase (PHD2) and histone deacetylase 6 (HDAC6). The compound is expected to become a novel acute kidney injury treatment medicine.

Provided is a method for preparing a recombinant human collagen. The method comprises: constructing a genetically engineered bacterium which expresses a prolyl hydroxylase and a recombinant human collagen; culturing the genetically engineered bacterium and performing digestion treatment by means of pepsin to obtain a recombinant human collagen type I or type III. The prolyl hydroxylase comprises P4Ha2, P4Hb and vP4H, and by means of controlling the ratio of the copy numbers of the genes thereof, the recombinant human collagen and a natural human collagen are consistent in hydroxylation modification. Also provided is a large-scale production method for the recombinant human collagen. The prepared recombinant human collagen has completely the same sequence composition and length and substantially the same hydroxyproline content as the natural human collagen, and also has a stable full-length triple helix structure and biological activity without immunogenicity and potential risk of viruses.

Described herein are crystalline forms of small molecule inhibitor compounds (1) of Prolyl Hydroxylase Domain-containing Protein (PHD) and pharmaceutical compositions thereof, and methods of their use in the treatment of diseases or conditions that would benefit from treatment with inhibitors of Prolyl Hydroxylase Domain-containing Protein (PHD). (1)

Described herein are methods of treating inflammatory bowel disease using prolyl hydroxylase domain-containing protein (PHD) inhibitors and additional active agents.

The invention discloses a prolyl hydroxylase inhibitor, and belongs to the technical field of medicines. The invention provides a pyridinotriazole compound, the structure of which is shown in the following formula, and the pyridinotriazole compound has higher prolyl hydroxylase inhibitory activity and EPO induction activity, can effectively treat and prevent HIF-related and / or EPO-related diseases, and provides a new thought for anemia, ischemia, hypoxia and other diseases. # imgabs0 #

The present invention relates to systems and compositions for editing of prolyl hydroxylase domain-containing protein (PHD) gene, and method of inhibiting PHD (e.g., for use in treating retinal degenerative diseases). Particularly the present disclosure provides systems, compositions, and methods for editing and / or ablation of the prolyl hydroxylase domain-containing protein 2 (PHD2) gene.

CRYSTALLINE FORMS OF SMALL MOLECULE INHIBITORS OF PROLYL HYDROXYLASE DOMAIN-CONTAINING PROTEINS (PHD), AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME AND METHODS OF USE THEREOF Compound 1

This specification describes the crystalline form of compound (1), which is a low-molecular-weight prolyl hydroxylase domain-containing protein (PHD) inhibitor, its pharmaceutical composition, and its use in the treatment of diseases or conditions for which treatment with a prolyl hydroxylase domain-containing protein (PHD) inhibitor is beneficial. TIFF2026513705000031.tif32170

Provided is a method, a kit, and a device for determining whether there is incidence of dementia or whether there is a risk of onset of dementia in a human subject using a biomarker that allows highly sensitive and specific determination by a simple operation. The method includes the step of calculating the ratio(s) between the expression level(s) of the connexin 43 gene and / or the prolyl hydroxylase domain-containing protein 3 gene, and the expression level of the connexin 37 gene.

Provided herein are methods and compositions comprising pharmacological inhibitors of HIF hydroxylases (e.g., or more inhibitors of Prolyl Hydroxylase Domain enzymes (PHDs) or Factor Inhibiting HIF (FIH)) for enhancing cyanide resistance in living organisms.

The invention relates to a new function of an aromatic organic acid compound, and belongs to the technical field of biology. By utilizing a prolyl hydroxylase 2 small molecule compound inhibitor screening system, the aromatic organic acid compound is found to be capable of effectively inhibiting the activity of prolyl hydroxylase 2. The aromatic organic acid compound improves the protein level of an intracellular hypoxia-inducible factor HIF-1alpha by inhibiting the activity of prolyl hydroxylase 2.

An application of a prolyl hydroxylase domain 2 (PHD2) in preparation of drugs for prevention and treatment of platelet thrombus is provided and relates to the field of biomedical technology. The important role of PHD2 protein in the process of platelet adhesion and thrombus formation is provided, PHD2 as a regulatory target of platelet adhesion is also provided, and thrombus formation can be significantly inhibited by knocking down PHD2 gene expression. This provides new technological ways for the development of drugs for antiplatelet thrombus and the improvement of blood microcirculation disorders. The PHD2 inhibitor can inhibit platelet thrombus by inhibiting PHD2, thereby providing new therapeutic options and candidate drugs for the prevention and / or treatment of platelet thrombus diseases due to platelet excessive activation (including, but not limited to arterial thrombosis, such as heart attack and stroke, and venous thrombus diseases, such as pulmonary embolism and deep vein thrombosis).

Disclosed herein are new therapeutic methods comprising administering compounds that can stabilize HIF and inhibit HIF prolyl hydroxylase (HIF-PH). In particular, methods described herein can be useful for treating / preventing a disease or condition in patients in need thereof, such as a patient having a viral infection such as a respiratory and / or pulmonary viral infection (e.g., an infection such as COVID-19 or a coronavirus infection). Methods described herein can also be useful for treating / preventing organ injury (e.g. organ injury that occurs concurrently or as a result of an infection). For example, methods described herein can be useful for treating or preventing acute lung injury, acute respiratory distress syndrome (ARDS), cardiovascular injury, injury to the liver, kidney diseases, and / or multi-organ failure.

Disclosed are processes for preparing [(3-hydroxypyridine-2-carbonyl)amino]-alkanoic acids, derivatives, inter alia, 5-aryl substituted and 5-heteroaryl substituted [(3-hydroxypyridine-2-carbonyl]amino}acetic acids. Further disclosed are methods for making prodrugs of [(3-hydroxypyridine-2-carbonyl)-amino]acetic acids, for example, [(3-hydroxypyridine-2-carbonyl]amino}acetic acid esters and {[3-hydroxypyridine-2-carbonyl]amino}acetic acid amides. The disclosed compounds are useful as prolyl hydroxylase inhibitors or for treating conditions wherein prolyl hydroxylase inhibition is desired.

Disclosed herein are new therapeutic methods comprising administering compounds that can stabilize HIF and inhibit HIF prolyl hydroxylase (HIF-PH). In particular, methods described herein can be useful for treating / preventing a disease or condition in patients in need thereof, such as a patient having a viral infection such as a respiratory and / or pulmonary viral infection (e.g., an infection such as COVID-19 or a coronavirus infection). Methods described herein can also be useful for treating / preventing organ injury (e.g. organ injury that occurs concurrently or as a result of an infection). For example, methods described herein can be useful for treating or preventing acute lung injury, acute respiratory distress syndrome (ARDS), cardiovascular injury, injury to the liver, kidney diseases, and / or multi-organ failure.

The application belongs to the field of biological medicine, discloses a HIF prolyl hydroxylase 2 inhibitor as shown in formula (I), relates to a 4-quinazolinone compound and a preparation method thereof, further relates to a pharmaceutical composition containing the compound and purposes. The HIF prolyl hydroxylase mediated disease in the application is selected from the group of uses in anemia secondary to or associated with chronic kidney disease, anemia associated with or caused by chemotherapy or anemia associated with AIDS.

Described herein are PHD inhibitors and pharmaceutical compositions comprising said inhibitors. The subject compounds and compositions are useful for the treatment of anemia.

Crystalline form of small molecule prolyl hydroxylase domain-containing protein (PHD) inhibitors, their pharmaceutical compositions, and methods of use thereof in the treatment of anemia. TIFF2026513421000019.tif27170 Compound 1.

The present invention relates to the substance sebparin or a pharmaceutically acceptable salt thereof for use in the treatment of subjects with chronic kidney disease (CKD), which may also include anemia. This therapy may also be useful as a combination therapy with standard of care (SOC) therapies, such as erythropoiesis-stimulating agents (ESAs) or HIF prolyl hydroxylase inhibitors.

The present invention provides a preparation method for extracting volatile oil from Chimonanthus salicifolius leaves by ultrasonic-assisted steam distillation and its application in drugs for improving ulcerative colitis. The method includes crushing the Chimonanthus salicifolius leaves to a specific particle size and then performing ultrasonic treatment and steam distillation under optimized conditions, ultimately achieving a high extraction efficiency of 2.5% - 4%. The volatile oil is rich in phellandrene, α-terpineol, and (+)-limonene, accounting for more than 50% of the total mass. Pharmacological experiments show that this volatile oil can significantly reduce the levels of pro-inflammatory factors interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the serum of mice, increase the anti-inflammatory factor interleukin-10 (IL-10); increase the expression of tight junction protein ZO-1, protect the integrity of the intestinal epithelial barrier of mice; and significantly down-regulate the expression of the prolyl hydroxylase 3 factor in the HIF-1 pathway to inhibit inflammation.

The purpose of the present invention is to provide a biomarker with which it is possible to determine the presence or absence of dementia with high sensitivity and specificity by means of a simple operation, and to provide a method, a kit, and a device for the determination. Provided is a method for determining the presence or absence of a risk of dementia in a subject, said method comprising a step for calculating the expression level of connexin 43 gene and / or the ratio of the expression level of prolyl hydroxylase domain protein 3 gene to the expression level of connexin 37 gene.