51 results about "BCL6" patented technology

This disclosure provides compounds of Formula (I) (e.g., Formula (I-a), (I-a1), (I-b), or (I-c)), or pharmaceutically acceptable salts thereof, that induce degradation of a BCL6 protein. These compounds are useful, for example, for treating a cancer in a subject (e.g., a human). This disclosure also provides compositions containing compounds of Formula (I) (e.g., Formula (I-a), (I-a1), (I-b), or (I-c)), or pharmaceutically acceptable salts thereof, as well as methods of using and making the same

Bifunctional compounds, which find utility as modulators of B-cell lymphoma 6 protein (BCL6; target protein), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand that binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation / inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Provided herein are compounds and compositions thereof for modulating BCL6. In some embodiments, the compounds and compositions are provided for treatment of cancer or an autoimmune disease. In a particular embodiment, the compounds are of Formula (I):, wherein values for the variables are as described herein.

This disclosure provides compounds of Formula (I) (e.g., Formula (I-a) or (I-a1)) or Formula (II), or pharmaceutically acceptable salts thereof, that induce degradation of a BCL6 protein. These compounds are useful, for example, for treating a cancer in a subject (e.g., a human). This disclosure also provides compositions containing compounds of Formula (I) (e.g., Formula (I-a) or (I-a1)) or Formula (II), or pharmaceutically acceptable salts thereof, as well as methods of using and making the same.

Provided herein are compounds and compositions thereof for modulating BCL6. In some embodiments, the compounds and compositions are provided for treatment of cancer or an autoimmune disease. In a particular embodiment, the compounds are of Formula (I):, wherein values for the variables are as described herein.

The invention discloses an application of a cytokine LYG1 in preparation of a medicine for treating immune-related diseases. According to the present invention, the regulation effect and the mechanism of LYG1 in Tfh cells and cGVHD are deeply researched, such that the following important research results are obtained: the deletion of LYG1 inhibits the Tfh cell differentiation and the expression of characteristic molecules (BCL6, CXCR5, ICOS, TOX2 and the like), and the GC-B cell ratio and the antibody generation are reduced; the invention can be used for drugs and vaccines for autoimmune diseases such as cGVHD, immunodeficiency diseases and infectious diseases.

Methods are provided for generating unlimited immune cells with increased lifespan and high proliferation rate by modifying them to express BCL6 and genes that promote cell survival. Further methods are provided for generating and using said unlimited immune cells to treat diseases such as cancer.

The present disclosure provides compounds of Formula (I) (e.g., Formula (I-1), Formula (Ia) (e.g., Formulas (Ia-1), (Ia-2), (Ia-3), (Ia-4), (Ia-5), or (Ia-6)), or Formula (Ib) (e.g., Formula (Ib-1) or (Ib-2)) or pharmaceutically acceptable salts thereof, which induce degradation of BCL6 protein. These compounds are useful, for example, for treating cancer in a subject (e.g., a human). The present disclosure also provides compositions containing the compounds and methods of using and preparing them.

Described are the compounds, compositions and methods of treating a disease or disorder characterized by aberrant B-cell lymphoma 6 (BCL6) activity.

The application discloses a kind of bivalent ligand molecules for targeting BCL6 protein degradation and application thereof, it is related to the technical field of drug development;The structure general formula of the bivalent ligand molecules for targeting BCL6 protein degradation is as follows: M1-L-M2;Wherein, M1 and M2 are independent structure same or different BCL6 protein ligand;L is any chain or cyclic hydrocarbon fragment capable of forming covalent bond with BCL6 ligand.The application also provides the application of the bivalent ligand molecules in the preparation of anti-tumor and / or immune disease drugs.The bivalent ligand molecules can exert good anti-tumor activity on a variety of BCL6-dependent tumors by selectively inducing BCL6 protein degradation, and are also related to the occurrence of a variety of immune diseases, and can be used in related tumor and immune disease drugs.

The invention discloses a tricyclic BCL6 degradation agent and application of the tricyclic BCL6 degradation agent. The tricyclic compound or the pharmaceutically acceptable salt and solvate thereof provided by the invention are novel in structure, and have a relatively excellent degradation effect on BCL6 protein. Therefore, the compound provided by the invention or the composition containing the compound provided by the invention has a prospect of being developed into drugs for treating diseases which are treated or relieved by degrading the BCL6 protein; cancer such as Hodgkin's lymphoma, B-cell-derived non-Hodgkin's lymphoma, T-cell-derived non-Hodgkin's lymphoma, NK / T-cell-derived non-Hodgkin's lymphoma or diffuse large B-cell lymphoma and the like can be used in the preparation of drugs.

Provided herein are compositions and methods for treating an autoimmune disease or disorder in a subject. In some cases, the compositions and methods use chemical inducers of proximity (CIPs). In some cases, the CIPs include a first moiety having specific binding for a BTB domain-containing protein or a transcriptional repressor expressed in B cell subpopulations and a second moiety having specific binding for a modulator of gene regulation. In some cases, the BTB domain-containing protein comprises BCL6. In some cases, the transcriptional repressor expressed in B cell subpopulations is PRDM1 or IRF4. In some cases the modulator of gene regulation comprises BRD4, CDK9, and / or p300.

This application pertains to the use of Compound (A): or a pharmaceutically acceptable salt thereof, for the treatment of various diseases or disorders, including, for example, advanced non-Hodgkin lymphoma (NHL), relapsed / refractory (R / R) non-Hodgkin lymphoma (NHL), transformed follicular lymphoma, nodal T-follicular helper cell lymphoma (nTFHL), relapsed / refractory (R / R) nodal T-follicular helper cell lymphoma, nodal T-follicular helper cell lymphoma - angioimmunoblastic type (nTFHL- Al) / advanced angioimmunoblastic T-cell lymphoma (AITL), or relapsed / refractory (R / R) nodal T-follicular helper cell lymphoma - angioimmunoblastic type (nTFHL-AI) / angioimmunoblastic T-cell lymphoma (AITL).

The invention discloses a protein targeted degradation chimera and application thereof.The protein targeted degradation chimera is novel in chemical structure, has an excellent degradation effect on BCL6 protein, can be used for preparing BCL6 degradation agent medicine, has the prospect of being developed into medicine for treating diseases treated or relieved by degrading the BCL6 protein, and has a good application prospect. The diseases treated or relieved by degrading the BCL6 protein comprise cancers such as Hodgkin's lymphoma, B cell-derived non-Hodgkin's lymphoma, T cell-derived non-Hodgkin's lymphoma, NK / T cell-derived non-Hodgkin's lymphoma, diffuse large B cell lymphoma and the like.

The present application relates to the technical field of multi-gene detection, and in particular to a set of capture probes for follicular lymphoma multi-gene detection, a kit and a detection analysis method ARID1A, ARID1B, ATM, ATP6V1B2, B2M, BCL10, BCL2, BCL6, BCL7A, BTG1, BTG2, BTK, CARD11, CCND3, CD58, CD70, CD79A, CD79B, CDK4, CDKN2A The capture probe set comprises capture probes for specifically binding to 74 follicular lymphoma related genes, and the capture probe set preferably comprises nucleotides with sequences as shown in SEQ ID NO. 1-937. The probe set of the present application can realize one-time detection of variation in the full exon region of 74 follicular lymphoma related genes in the sample to be detected in the same system, has high specificity, high average sequencing depth and wide coverage area.

The present invention relates to a compound represented by general formula (I) or a stereoisomer, a deuterated form, a solvate, a prodrug, a metabolite, a pharmaceutically acceptable salt or a eutectic thereof, and an intermediate and a pharmaceutical composition thereof, and use thereof in Bcl6-related diseases such as cancer. B-L-K (I).

The invention discloses an anti-BCL6 protein nano antibody, a fusion protein and application thereof, and belongs to the technical field of biology. According to the invention, the nano antibody specifically targeting BCL6 is designed by using an artificial intelligence technology, and the nano antibody has good specificity and high affinity, and can efficiently bind to a BCL6 antigen; furthermore, rational design of the nano-antibody is carried out through artificial intelligence, so that a nano-antibody mutant with higher affinity is obtained; furthermore, a nano antibody or a nano antibody mutant with high affinity and relatively good specificity is fused with an RBCC structural domain or a mutant thereof to obtain a fusion protein, and the fusion protein can utilize the specificity of the nano antibody structural domain to bind to a target protein and start a protein degradation pathway, so that targeted degradation of the BCL6 protein is realized, and the BCL6 protein can be degraded in a targeted manner. The expression of cancer suppressor genes p53 and cyclin p21 in cells is improved, and the method has a very great clinical application value.

The present invention relates to compounds of formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity:wherein X1, X2, R1, R2, R30, R31 and Ring A are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.

The invention relates to application of targeted BCL6 regulation and control of Treg cells in preparation of anti-tumor drugs and application of targeted BCL6 regulation and control of Treg cells combined with immune checkpoint blocking agents in preparation of anti-tumor drugs, a BCL6 targeting method comprises the step of using a BCL6 inhibitor, experiments prove that the methylation level of H3K4 of Treg cell histone of BCL6 knockout mice is remarkably reduced, and the methylation level of H3K4 is remarkably reduced. Compared with the prior art, the anti-PDL1 group and the combined group have the advantages that the anti-PDL1 group and the combined group have better tumor inhibition efficacy, the inhibition capability on CD8T cells is obviously reduced, after the BCL6 inhibitor is used, compared with a control group, the tumor volume is obviously reduced, a targeting BCL6 regulation and control Treg cell combined immune checkpoint blocking agent shows a synergistic effect, the tumor size can be obviously inhibited, and compared with the anti-PDL1 group and the combined group, the anti-PDL1 group and the combined group have better tumor inhibition efficacy, and the anti-PDL1 group and the combined group have obvious difference; according to the invention, the efficacy of tumor immunotherapy is effectively improved, and a new direction and inspiration are provided for related research in the field.

Provided are compounds of the Formula PTM-L-CLM, or a pharmaceutically acceptable salt thereof, wherein the PTM is (PTM-I) These compounds are useful for the degradation of BCL6 and in the treatment cancer.

Provided herein are compounds and compositions thereof for modulating BCL6. In some embodiments, the compounds and compositions are provided for the treatment of cancer or autoimmune diseases.

Provided herein are compounds and compositions thereof for modulating BCL6. In some embodiments, compounds and compositions for the treatment of cancer or autoimmune diseases are provided. # imgabs0 #

The present disclosure provides a compound of Formula (I) (e.g., Formula (I-a), (I-a1), (I-b), or (I-c)) or a pharmaceutically acceptable salt thereof that induces degradation of a BCL6 protein. These compounds are useful, for example, in the treatment of cancer in a subject (e.g., a human). The disclosure also provides compositions containing a compound of Formula (I) (e.g., Formula (I-a), (I-a1), (I-b), or (I-c)), or a pharmaceutically acceptable salt thereof, as well as methods of using and preparing these compositions.

The present application relates to the use of compounds, such as Compound A: or a pharmaceutically acceptable salt thereof, for the treatment of various diseases or conditions, including, for example, diffuse large B-cell lymphoma (DLBCL) and vascular immunoblastic T-cell lymphoma.

The present invention provides a method of diagnosing endometriosis and / or infertility in a subject, comprising: a) obtaining a sample from the subject; b) detecting a level of expression of a SIRT1 gene and / or protein in the sample; c) detecting a level of expression of a BCL6 gene and / or protein in the sample; d) comparing the level of expression detected in (b) with the level of expression of a SIRT1 gene and / or protein in a sample obtained from a control subject or a population of control subjects; e) comparing the level of expression detected in (c) with the level of expression of a BCL6 gene and / or protein in a sample obtained from a control subject or a population of control subjects; and f) diagnosing the subject as having infertility when the subject has a level of expression of the SIRT1 gene and / or protein greater than the level of expression of the SIRT1 gene and / or protein of the control subject or population of control subjects and also has a level of expression of the BCL6 gene and / or protein that is greater than the level of expression of the BCL6 gene and / or protein of the control subject or population of control subjects.

Compounds, compositions, and methods for treating cancers characterized by abnormal B-cell lymphoma 6 (BCL6) activity are described.

The present disclosure relates to methods of treating cancer in a subject, comprising administering to the subject an effective amount of Compound A, or a pharmaceutically acceptable salt thereof, and an effective amount of an additional anti-cancer agent.

This disclosure provides compounds of Formula (I) (e.g., Formula (I-aa) (e.g., Formula (I-aa-1), (I-aa-2), (I-aa-3), (I-aa-4), (I-aa-5), or (I-aa-6)), Formula (I-a) (e.g., Formula (I-a-1), (I-a-2), (I-a-3), (I-a-4), (I-a-5), or (I-a-6)), Formula (I-bb) (e.g., Formula (I-bb-1) or (I-bb-2)), or Formula (I-b) (e.g., Formula (I-b-1) or (I-b-2))) or Formula (II), or a pharmaceutically acceptable salt thereof, that induce degradation of a BCL6 protein. These compounds are useful, for example, for treating a cancer in a subject (e.g., a human). This disclosure also provides compositions containing the compounds provided herein as well as methods of using and making the same.

The present disclosure relates to bifunctional compounds, their preparation, and the use of these bifunctional compounds in the treatment of a disease or condition caused by the aggregation or accumulation of B cell lymphoma 6 protein in a subject in need thereof.

The present application relates to the technical field of antitumor drugs, and particularly relates to a kind of PROTACs compound targeted to degrade BCL6 and application thereof, and the compound is the compound shown in formula (I) or its stereoisomer, geometric isomer, tautomer, nitroxide, solvate, pharmaceutically acceptable salt, metabolite or prodrug.The PROTACs compound targeted to degrade BCL6 provided in the present application connects BCL6 protein ligand and E3 ubiquitin ligase ligand through chemical groups;The compound can be used to inhibit the proliferation, growth, migration, infiltration, clonal formation and metastasis of tumor cells, promote the apoptosis of cancer cells, promote the autophagy of tumor cells, overcome the drug resistance of chemotherapy or targeted therapy of tumor, inhibit the growth of tumor stem cells, and prolong the survival period of tumor patients.