25 results about "Ubiquitin specific protease" patented technology

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.

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.

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.

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 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)

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 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.

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.

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 present application provides small molecules targeting ubiquitin specific protease 1 (USP1), and / or pharmaceutical compositions comprising the same, which can be used to treat diseases or disorders caused by diseases or disorders associated with ubiquitin specific protease 1 (USP1), such as, but not limited to, cancer, and other diseases or conditions associated with DNA damage, etc., particularly cancer associated with BRCA1 or BRCA2 mutations.

The disclosure provides for small molecules inhibitory compounds of ubiquitin specific protease 1 (USP1) and compositions comprising the same. The disclosure further provides 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 technical field of biological medicine, and particularly relates to a 2-acylamino-N-aryl benzamide derivative and application of the 2-acylamino-N-aryl benzamide derivative to a ubiquitin specific protease 2 (USP2) inhibitor. The 2-acylamino-N-arylbenzamide derivative provided by the invention has relatively strong USP2 protein inhibitory activity, can effectively inhibit tumor cell proliferation, is simple in synthesis process and relatively low in cost, can be applied to preparation of drugs for treating and / or preventing diseases related to USP2 activity abnormality, has relatively good development potential, and can be applied to preparation of drugs for treating and / or preventing diseases related to USP2 activity abnormality. And a selectable range is provided for medicines for treating USP2 related diseases.

The invention discloses a heterocyclic amide compound as well as a preparation method and application thereof. Specifically, the heterocyclic amide compound provided by the invention has a structure as shown in a formula (I), can be used as an ubiquitin specific protease 1 (USP1) inhibitor, and can be used for preparing medicines for diagnosing and / or treating and / or preventing diseases related to the ubiquitin specific protease 1 (USP1), especially medicines for diagnosing and / or treating and / or preventing tumors or cancers. .

The invention provides application of ubiquitin specific protease 33 in regulation and control of polarization of macrophages and anti-tumor and / or anti-infection, and belongs to the technical field of biological medicine manufacturing. The invention discloses ubiquitin specific protease 33 serving as a new immune activation target to participate in polarization of M1 type macrophages. The invention reveals that USP33 regulates and controls the protein stability of the IRF2 factor through a ubiquitination modification way for the first time, and further regulates and controls the expression of downstream inflammatory cytokines such as INF-gamma. The USP33 is knocked out or knocked down to degrade the IRF2, so that the inhibition effect of the IRF2 on a proinflammatory signal is relieved, the polarization of macrophages to M1 type is promoted, the expression of proinflammatory factors is up-regulated, the proliferation of tumor cells is inhibited, and the growth of tumors is remarkably inhibited; and meanwhile, the defense capability of the host to the Listeria monocytogenes can be enhanced by virtue of myeloid specific knockout of the USP33.

The invention belongs to the technical field of biological genes, and particularly relates to application of USP38 serving as a target in screening of drugs for treating or preventing liver cancer. The invention provides the application of the ubiquitin specific protease 38 (USP38) gene in the malignant progression of the hepatocellular carcinoma, the function and mechanism of the cell cycle key protein CDK1 regulation gene USP38 in the hepatocellular carcinoma (HCC) are found, a more effective targeted therapy strategy is expected to be developed, and a better clinical effect is brought to HCC patients. Experimental results show that the proliferation, migration / invasion of tumor cells can be inhibited by knocking down the USP38, so that the fact that the USP38 gene can regulate and control the generation and development of HCC is further determined. Therefore, the USP38 can be used as a drug target for screening the drugs for treating the liver cancer, and the USP38 inhibitor can be used for preparing the drugs for treating and reversing the liver cancer.

The present disclosure relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof and pharmaceutical composition comprising the compound of formula (I). The present composition also relates to methods treating a disease or disorder associated with ubiquitin-specific protease 28 (USP28), methods of treating cancer, and methods of inhibiting USP28.