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BCL6 inhibitors and degraders act on B-cell lymphoma 6 (BCL6), a transcriptional repressor in B cells. The BCL6 gene was first identified through chromosomal alterations in diffuse large B-cell lymphoma (DLBCL), and BCL6 is required for germinal center B cells. A small molecule that blocks BCL6 repressor activity was shown to kill DLBCL cells in vitro and in vivo, which made the protein a research target in lymphoma. Listed inhibitors include FX1 and BI-3812, while BI-3802 and the proteolysis-targeting chimera (PROTAC) ARV-393 lower BCL6 protein levels. The section also holds molecular glues such as TCIP3 and building blocks for degrader synthesis.
Synonyms: U52
BI-3802 is a highly potent BCL6 degrader, inhibiting the BTB domain of BCL6, with an IC50 of ??3 nM; BI-3802 has antitumor activity.
ARV-393 is a potent BCL6 PROTAC degrader that facilitates the ubiquitination and subsequent proteasomal degradation of BCL6. This compound exhibits significant biological activity and is particularly relevant for research focused on advanced non-Hodgkin lymphoma. Its ability to modulate protein levels through targeted degradation makes it a valuable tool for elucidating BCL6-related pathways in cancer biology.
PROTAC BCL6/GSPT1 Degrader-1 is a dual-target PROTAC that effectively degrades both BCL6 and GSPT1 proteins. This compound is associated with the inhibition of cell proliferation, along with the induction of DNA damage, cell cycle arrest, and apoptosis, specifically in diffuse large B-cell lymphoma. It serves as a valuable tool for research into tumor biology, particularly in the context of lymphoma and related malignancies.
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MNN-02-155 is a bivalent molecular glue that binds simultaneously to p300/CBP and BCL6. This compound effectively activates the BCL6-target reporter gene, leading to significant induction of cell death. MNN-02-155 is particularly relevant for research into diffuse large B cell lymphomas (DLBCLs), providing insights into potential therapeutic strategies involving BCL6 modulation.
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TCIP3 is a bivalent molecular glue that targets p300/CBP and BCL6. By redirecting p300 and CBP, TCIP3 activates programmed cell death genes that are typically suppressed by the oncogenic driver BCL6, making it a valuable tool for investigating diffuse large B cell lymphomas (DLBCLs). Importantly, TCIP3 demonstrates no toxicity to non-transformed tonsillar lymphocytes or fibroblasts, ensuring the safety of experimental applications.
BMS-986458 is a selective cereblon-based BCL6 degrader that exerts antitumor effects through the targeted degradation of the BCL6 protein. By binding to cereblon and interacting with the BTB domain of BCL6, it modulates key pathways such as cell cycle regulation, antiproliferative signals, and interferon responses, while also enhancing CD20 expression and distribution. BMS-986458 influences follicular helper T cell physiology and reduces circulating tumor DNA levels. Its combination with CD20xCD3 bispecific antibodies has been shown to improve T cell infiltration and expansion in tumors. This compound is applicable in research related to B-cell non-Hodgkin lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, and relapsed/refractory lymphoma.
PROTAC BCL6 Degrader-3 is a selective degrader targeting the BCL6 protein through the proteolysis-targeting chimera (PROTAC) approach. This compound mediates the ubiquitination and subsequent degradation of BCL6, facilitating the modulation of pathways associated with cancer and autoimmune diseases. It serves as a valuable tool for researchers exploring therapeutic strategies aimed at BCL6 inhibition and the underlying mechanisms of related diseases.
BCL6-760 is an orally active BCL-6 PROTAC degrader that selectively targets and degrades BCL-6 with an EC50 of 0.8 nM, without affecting other CRBN substrates. This compound exhibits notable efficacy in orthotopic xenograft mouse models of OCI-LY-1 tumors. BCL6-760 serves as a valuable tool for investigating diffuse large B-cell lymphoma (DLBCL) and for exploring mechanisms related to BCL-6 signaling pathways in cancer research.
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BCL6 PROTAC 1 is a selective proteolysis targeting chimera (PROTAC) that targets B-cell lymphoma 6 (BCL6) for degradation. It exhibits potent inhibitory activity on BCL6 cell reporter assays, with an IC50 value of 8.8 µM. This reagent effectively induces degradation of BCL6 in diffuse large B-cell lymphoma (DLBCL) cell lines, making it a valuable tool for tumor-related research applications.
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BCL6-IN-10 is a selective molecular glue inhibitor that targets the BTB domain of BCL6, exhibiting an IC50 of 4 nM. This compound demonstrates significant anti-proliferative activity in diffuse large B-cell lymphoma (DLBCL) cell lines, making it a valuable tool in cancer research. Its unique mechanism of action offers insights into therapeutic strategies for targeting BCL6-associated malignancies.
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ALV-05-077-01 is a selective degrader of BCL6 and BCL6B proteins. It effectively reduces endogenous BCL6 levels in SuDHL4 cells and BCL6B levels in KYO1 cells, both of which exhibit high expression of these proteins. This compound is useful for investigating the role of BCL6 and BCL6B in hematological malignancies and provides insight into potential therapeutic strategies targeting these proteins.
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ALV-05-151-02 is a degrader of BCL6 and BCL6B, effectively reducing endogenous BCL6 levels in SuDHL4 cells and BCL6B levels in KYO1 cells, which exhibit high expression of these targets. This compound serves as a valuable tool for researching hematological malignancies by facilitating the study of the role of BCL6 and BCL6B in various malignancies.
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