41 results about "Ubiquitin specific protease" patented technology

Disclosed herein are inhibitors of deubiquitinating (DUB) enzyme USP7 (Ubiquitin Specific Protease 7). Also provided are methods of treating a disease or disorder modulated by USP7.

Provided are a compound represented by general formula (I′), a method for preparing same, a pharmaceutical composition comprising same, and use thereof as a ubiquitin specific protease 1 (USP1) inhibitor, in particular, use thereof in treating or preventing a cancer.

The disclosure relates to methods for treating cancers (e.g., cancers having a BRCA1 and / or BRCA2 mutation(s)) by administering to the subject an effective amount of a ubiquitin-specific protease 1 (USP1) inhibitor.

The invention belongs to the technical field of gene engineering, and particularly relates to a medicine for treating AML (acute myelogenous leukemia) and / or prognosis of AML patients and application of ubiquitin specific protease 20 serving as a target spot in treating acute myelogenous leukemia. The invention provides a medicine for treating AML (acute myelogenous leukemia) and / or prognosis of an AML patient and application of ubiquitin specific protease 20 as a target spot in treating acute myelogenous leukemia, USP20 is used as a super enhancer regulation gene, and the progress of the AML is promoted by combining with CTNNB1, ERG, ELF1 and RUNX1. The knock-down of the USP20 can significantly inhibit AML proliferation in vivo and in vitro. The wnt-beta-catenin pathway can be influenced by interfering the expression of the USP20 so as to influence the progress of AML (acute myeloid leukemia). And the inhibition effect of the inhibitor AS1517499 subjected to virtual screening on the growth of the AML cells is superior to that of a commercial inhibitor GSK2643943A of USP20.

Provided herein are small molecules inhibitory compounds of ubiquitin specific protease 1 (USP1) and compositions comprising the same. Further provided herein are methods for targeting ubiquitin specific protease 1 (USP1) and methods of treating diseases or disorders related to USP1, such as cancer.

The invention belongs to the field of medicinal chemistry, and relates to carbonyl fused heterocyclic derivatives used as ubiquitin-specific protease inhibitors, in particular to a compound shown in the formula (I), an isomer thereof or pharmaceutically acceptable salt thereof.

The present invention relates to a compound having a novel structure and ubiquitin-specific protease 1 (USP1) inhibitory activity, a stereoisomer thereof, or pharmaceutically acceptable salts thereof, use thereof for preparing a therapeutic drug, a pharmaceutical composition containing same, a therapeutic use and method using the composition, and a method for preparing same. The compound having a novel structure and USP1 inhibitory activity is represented by Formula Ia, Ib, or Ic.

The invention discloses a preparation method, application and application of a pyridazinone compound as a ubiquitin-specific protease 1 inhibitor, and particularly discloses a compound as shown in a formula (I), an optical isomer, a tautomer or pharmaceutically acceptable salt of the compound, and application of the compound as the ubiquitin-specific protease 1 inhibitor.

A compound represented by formula I and a racemate, a stereoisomer, a tautomer, an isotopic marker, nitrogen oxide, a solvate, a polymorph, a metabolite, an ester, a pharmaceutically acceptable salt or a prodrug thereof, a pharmaceutical composition comprising same, a preparation method therefor, and a pharmaceutical use thereof are described. The compound has the activity of inhibiting USP28 and / or USP25. The structure of the formula I is as follows.

The invention provides a polypeptide for inhibiting tumor immune escape and application thereof. The polypeptide is a peptide derived from 181-190 amino acids at the amino terminal of ubiquitin specific protease 15 (USP15), enters tumor cells by means of a cell-penetrating peptide CPP, and can obviously block the combination of USP15 and PD-L1 in the tumor cells, promote ubiquitination degradation of PD-L1, obviously lower the level of tumor cells PD-L1, inhibit tumor immune escape and play an in-vitro and in-vivo anti-tumor role. In addition, when the U10 polypeptide and the PD-1 monoclonal antibody (mAb) are jointly applied to a mouse body, the effect of synergistically resisting tumor immune escape is achieved. Therefore, the U10 polypeptide can be used as a new strategy of immune checkpoint blocking treatment, is used for tumor immunotherapy, and has important clinical application value.

The invention discloses a pyrimidine compound as well as a preparation method and medical application thereof. Specifically, the invention discloses a compound shown in a general formula (I), a preparation method of the compound, a pharmaceutical composition containing the compound, and application of the compound as a ubiquitin specific protease 1 (USP1) inhibitor, especially application of the compound in treating or preventing cancers. The definition of each group in the general formula (I) is the same as that in the specification.

JPEG2026525352000192.jpg3981 The present invention relates to compounds of formula (I) that are useful as inhibitors of ubiquitin-specific protease USP19 activity. The present invention also relates to pharmaceutical compositions comprising these compounds and methods of using these compounds in therapeutics.

The invention provides an application of USP7 (ubiquitin-specific protease 7) as a target spot in preparation of drugs for treating vascular abnormal leakage diseases, and relates to the technical field of biomedicine, USP7 (ubiquitin-specific protease 7) as a deubiquitination enzyme not only regulates tumor, nerve and immune related diseases, but also is closely related to vascular endothelial cell functions. In the vascular homeostasis, the USP7 can maintain the integrity of a vascular barrier and inhibit pathological leakage by stabilizing endothelial connexin such as VE-cadherin and beta-catenin; under the inflammation or hypoxia condition, through deubiquitination of HIF-1alpha or NF-kappa B pathway components (such as I kappa B alpha), vascular endothelial cell activation can be promoted, VEGF signal-driven abnormal angiogenesis or release of inflammatory factors can be aggravated, and diabetic retinopathy, tumor vascular hyperplasia and sepsis-related vascular leakage can be participated. According to the application, verification experiments prove that USP7 has a certain protection effect on vascular permeability, and a treatment strategy is provided for vascular abnormal leakage diseases clinically.

This invention relates to the field of pharmaceutical technology, specifically to ubiquitin-specific protease 1 inhibitor compounds, pharmaceutically acceptable salts, esters, deuterated derivatives or stereoisomers thereof, pharmaceutical compositions and formulations containing said compounds, pharmaceutically acceptable salts, esters, deuterated derivatives or stereoisomers thereof, methods for preparing said compounds, pharmaceutically acceptable salts, esters, deuterated derivatives or stereoisomers thereof, and the use of said compounds, pharmaceutically acceptable salts, esters, deuterated derivatives or stereoisomers thereof in the preparation of medicaments for the treatment and / or prevention of USP1-mediated diseases and related diseases.

The present application relates to the technical field of medicine, specifically relates to substituted tri-cyclic ubiquitin specific protease 1 (USP1) inhibitor compounds, pharmaceutically acceptable salts or stereoisomers thereof, pharmaceutical compositions and preparations containing the compounds, pharmaceutically acceptable salts or stereoisomers thereof, a method for preparing the compounds, pharmaceutically acceptable salts or stereoisomers thereof, and the use of the compounds, pharmaceutically acceptable salts or stereoisomers thereof in the preparation of drugs for treating and / or preventing diseases mediated by USP1 and related diseases.

Described herein are methods of treating cancer using a small molecule ubiquitin specific protease 1 (USP1) inhibitor and an additional agent.

The present invention relates to compounds of formula (I) useful as inhibitors of ubiquitin-specific protease USP19 activity. The invention also relates to pharmaceutical compositions comprising these compounds, and methods of using these compounds in therapy. (I)

The invention relates to the technical field of medical biology, in particular to application of Skepinone-L in killing neuroblastoma cells, and finds that the Skepinone-L can specifically kill the neuroblastoma cells and significantly inhibit proliferation, migration and clone formation capabilities of the neuroblastoma cells for the first time. An action mechanism research shows that the Skepinone-L accurately targets ubiquitin specific protease 7, and is combined with a key residue through a hydrogen bond to down-regulate USP7 expression and activate a downstream apoptosis pathway. Molecular dynamics simulation proves that the compound is high in stability. The invention provides a new candidate drug with high efficiency and low toxicity for neuroblastoma, and has remarkable clinical transformation potential.

The present invention relates to compounds of Formula (I) that are useful as inhibitors of the activity of the ubiquitin specific protease USP19. The present invention also relates to pharmaceutical compositions comprising these compounds and to methods of using these compounds in therapy.

Pyrimidine compounds, methods for preparing them, and their medical uses are disclosed. Specifically, compounds represented by general formula (SI), methods for preparing them, pharmaceutical compositions containing the compounds, and their use as ubiquitin-specific protease 1 (USP1) inhibitors, particularly for the treatment or prevention of cancer, are disclosed. The definitions of the groups in general formula (SI) are the same as those in the specification. JPEG2026523087000394.jpg25170

The present application relates to the technical field of medicine, and particularly relates to a tri-cyclic ubiquitin-specific protease 1 inhibitor compound, a pharmaceutically acceptable salt, an ester, a deuterium or a stereoisomer thereof, a pharmaceutical composition and preparation containing the compound, the pharmaceutically acceptable salt, the ester, the deuterium or the stereoisomer thereof, a method for preparing the compound, the pharmaceutically acceptable salt, the ester, the deuterium or the stereoisomer thereof, and an application of the compound, the pharmaceutically acceptable salt, the ester, the deuterium or the stereoisomer thereof in preparing a medicine for treating and / or preventing a disease mediated by USP1 and related diseases.

The invention belongs to the technical field of biology, and particularly relates to application of ubiquitin specific protease 4 as a diagnostic marker or a therapeutic target of high-grade serous cancer. According to the invention, the high expression of ubiquitin specific protease 4 (USP4) in high-grade serous cancer (HGSOC) tissue is found for the first time, and is obviously higher than that of normal fallopian tube tissue (plt; the application has the advantages that the expression level difference of the USP4 is related to the total survival time (OS) of a patient, survival analysis shows that the USP4 expression level difference is related to the total survival time (OS) of the patient, and the USP4 can be used as a diagnosis and prognosis evaluation marker of the high-grade serous cancer; moreover, CCK-8 and plate cloning experiments prove that the knock-down USP4 inhibits the proliferation of HGSOC cells and treats the high-grade serous cancer. USP4 may play a role in promoting cancer in the progress process of HGSOC.

The present invention provides a compound defined by Chemical Formula 1 or a tautomer thereof, and a pharmaceutically acceptable salt thereof. The compound provided by the invention can inhibit the activity of ubiquitin specific protease 1. [Chemical Formula 1]

The presently disclosed subject matter relates to compositions comprising Ubiquitin-Specific Protease 1 (USP1) inhibitors and methods of using the same.

The invention belongs to the technical field of medicines, and particularly relates to a substituted tri-fused ring ubiquitin specific protease 1 (USP1) inhibitor compound, pharmaceutically acceptable salt thereof, or a stereoisomer thereof, a pharmaceutical composition containing the compound, the pharmaceutically acceptable salt thereof, or the stereoisomer thereof, and a preparation containing the compound, the pharmaceutically acceptable salt thereof, or the stereoisomer thereof. The invention relates to a compound, a pharmaceutically acceptable salt or a stereoisomer thereof, a method for preparing the compound, the pharmaceutically acceptable salt or the stereoisomer thereof, and application of the compound, the pharmaceutically acceptable salt or the stereoisomer thereof in preparation of drugs for treating and / or preventing USPl-mediated diseases and related diseases.

Disclosed are a heterocyclic amide compound, a preparation method therefor, and a use thereof. Specifically, the heterocyclic amide compound involved in the present invention has a structure as shown in formula (I), can serve as a ubiquitin-specific protease 1 (USP1) inhibitor, and can be used for preparing a medicament for diagnosing and / or treating and / or preventing diseases related to ubiquitin-specific protease 1 (USP1), particularly a medicament for diagnosing and / or treating and / or preventing tumors or cancers.

The invention discloses a pyrimidine compound as well as a preparation method and medical application thereof. Specifically, the invention discloses a compound shown in a general formula (SI), a preparation method of the compound, a pharmaceutical composition containing the compound, and application of the compound as a ubiquitin specific protease 1 (USP1) inhibitor, especially application of the compound in treating or preventing cancers. The definition of each group in the general formula (SI) is the same as that in the description.

This invention discloses the application of ubiquitin-specific protease USP4 in the treatment of acute lung injury / acute respiratory distress syndrome (ARDS). Analysis of the GEO database revealed elevated USP4 levels in ARDS patients; in vitro stimulation of human neutrophils with LPS showed increased USP4 expression levels; experiments confirmed that the USP4 inhibitor Vialinin A effectively treats ARDS and significantly improves mouse survival; adenovirus inhibition of USP4 expression in the lungs effectively alleviates ARDS; and USP4 deficiency in the hematopoietic system effectively alleviates ARDS. This invention is the first to propose the application of USP4 as a target in screening drugs for the treatment of ARDS, providing a new target and a novel treatment strategy for clinical practice.

The invention relates to a preparation method, application and application of a nitrogen heterocyclic amine compound as a ubiquitin-specific protease 1 inhibitor, and particularly discloses a compound as shown in a formula (I), an optical isomer, a tautomer or pharmaceutically acceptable salt of the compound, and application of the compound as the ubiquitin-specific protease 1 inhibitor.

The invention discloses application of USP21 in diagnosis and treatment of abdominal aortic aneurysm, and belongs to the field of biological medicine. It is found that the ubiquitin specific protease 21 (USP21) level in abdominal aortic aneurysm tissue is obviously increased compared with normal abdominal aortic aneurysm tissue and is closely related to occurrence and development of abdominal aortic aneurysm (AAA), and further, by knocking down the USP21, the tumor formation rate of the abdominal aortic aneurysm can be reduced, the diameter of the abdominal aortic aneurysm can be reduced, and the conditions of elastic fiber breakage and the like can be improved. Therefore, the USP21 can be used as a diagnosis molecular marker of the abdominal aortic aneurysm and can also be used as a potential treatment target of the abdominal aortic aneurysm. The invention provides a more favorable means for diagnosis and treatment analysis of the abdominal aortic aneurysm, which is of great significance for research and treatment of the abdominal aortic aneurysm. Meanwhile, an experimental foundation is laid for developing high-efficiency related medicines for treating abdominal aortic aneurysm, and a new visual field is provided, so that the method has a good practical application value.