JP-2025517099-A5 -

Dates

Publication Date

20260508

Application Date

20230502

Description

In another aspect, in this specification, Equation (I): AB(I) A compound of, During the ceremony: (a) A is the first portion that shows specific binding to the first endogenous intracellular protein that binds to the target gene; (b) B is a second portion that exhibits specific binding to a second endogenous protein within the cell, distinct from the first endogenous protein; (c) The compound binds to the first endogenous protein and the second endogenous protein to form a complex, which can modulate the expression of the target gene in a manner dependent on the presence of the second endogenous protein within the complex. The complex modulates the expression of the target gene in less than approximately 16 hours or approximately 16 hours. Provides compounds. [Invention 1001] A method for treating subjects with diffuse large B-cell lymphoma (DLBCL), A step of administering to a subject an effective amount for treating DLBCL in which a proximity chemoinducer (CIP) that links BCL-6 to the estrogen receptor is administered. Methods that include... [Invention 1002] CIP The first ligand, which specifically binds to BCL-6, is covalently linked to a second ligand, which specifically binds to the estrogen receptor. A method of the present invention 1001, including the method of the present invention 1001. [Invention 1003] The method of the present invention 1001, wherein the administration of CIP activates the transcription of apoptosis-promoting genes to treat a subject for DLBCL. [Invention 1004] The method of the present invention 1003, wherein the apoptosis-promoting gene is selected from the group consisting of TP53, PUMA (BBC3), BIM (BCL2L11), BID, BAX, BAK, BOK, BAD, HRK, BIK, BMF, and NOXA. [Invention 1005] The method of the present invention 1001, wherein DLBCL is refractory DLBCL, and optionally the refractory DLBCL is CHOP-resistant DLBCL. [Invention 1006] A method for treating malignant tumors, A step of administering a transcriptional proximity chemoinducer (TCIP) that links BCL-6 and BRD4 to a subject in an amount effective for treating the subject for a malignant tumor. Methods that include... [Invention 1007] The method of the present invention 1006, wherein the administration of CIP activates the transcription of apoptosis-promoting genes to treat a target for malignant tumors. [Invention 1008] The method of the present invention 1007, wherein the apoptosis-promoting gene is selected from the group consisting of TP53, PUMA (BBC3), BIM (BCL2L11), BID, BAX, BAK, BOK, BAD, HRK, BIK, BMF, and NOXA. [Invention 1009] The method of the present invention 1006, wherein the malignant tumor is small cell lung cancer (SCLC) or diffuse large B-cell lymphoma (DLBCL). [Invention 1010] The method of the present invention 1001, comprising measuring the level of at least one of BRD4 and BCL6 within the target malignant cells to determine whether the malignant tumor is sensitive to treatment with TCIP, thereby assessing the target. [Invention 1011] A method for treating malignant tumors, A step of administering to a subject a transcriptional proximal chemoinducer (TCIP) that links BCL-6 (or its homolog) to an androgen receptor (AR) in an amount effective for treating the subject for a malignant tumor. Methods that include... [Invention 1012] The method of the present invention 1011, wherein the second ligand comprises an AR agonist. [Invention 1013] The method of the present invention 1011, wherein the second ligand comprises an AR antagonist. [Invention 1014] The method of the present invention 1011, wherein administration of TCIP activates the transcription of apoptosis-promoting genes to treat a target for malignant tumors. [Invention 1015] The method of the present invention 1014, wherein the apoptosis-promoting gene is selected from the group consisting of TP53, PUMA (BBC3), BIM (BCL2L11), BID, BAX, BAK, BOK, BAD, HRK, BIK, BMF, and NOXA. [Invention 1016] A method for treating malignant tumors, A step of administering to a subject a transcriptional proximal chemical inducer (TCIP) that links BCL-6 (or its homolog) to a cyclic-dependent kinase in an amount effective for treating the subject for a malignant tumor. Methods that include... [Invention 1017] The method of the present invention 1016, wherein the second ligand is selected from the group consisting of CDK9 ligand, CDK8 ligand, and CDK7 ligand. [Invention 1018] The method of the present invention 1017, wherein the second ligand is a CDK9 ligand. [Invention 1019] The method of the present invention 1016, wherein the administration of CIP activates the transcription of apoptosis-promoting genes to treat a target for malignant tumors. [Invention 1020] The method of the present invention 1019, wherein the apoptosis-promoting gene is selected from the group consisting of TP53, PUMA (BBC3), BIM (BCL2L11), BID, BAX, BAK, BOK, BAD, HRK, BIK, BMF, and NOXA. [Invention 1021] A method for regulating the expression of an intracellular target gene comprising a first e