| Hazard Information | Back Directory | [Description]
ARV-393 is an orally active proteolysis-targeting chimera (PROTAC) that utilizes the ubiquitin-proteasome system to target the degradation of BCL6. It consists of ligand conjugates that target BCL6 and the E3 ligase cereblon, respectively. ARV-393 has demonstrated DC50 and GI50 values of less than 1 nM in multiple cell lines of diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Additionally, it has shown considerable tumor suppressor activity in tumor xenograft models. ARV-393 is currently being studied for its potential to inhibit non-Hodgkin lymphoma.
| [Uses]
ARV-393 is a potent and orally active BCL6 PROTAC degrader. ARV-393 induces ubiquitination of BCL6 and its subsequent degradation by the proteasome. ARV-393 has the potential for the research of advanced non-hodgkin lymphoma[1][2][3]. | [Biological Functions]
ARV-393 is an investigational PROTAC designed to degrade B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas. The BCL6 protein facilitates B cell tolerance of rapid proliferation and somatic gene recombination via repressing cell cycle checkpoints, terminal differentiation, apoptosis, and the DNA damage response.
| [in vivo]
ARV-393 (3, 10, 30 mg/kg; po; once daily for 23 days) shows anticancer activity in xenograft model[3]. | Animal Model: | Mice (OCI-Ly1 cell line xenograft model)[3] | | Dosage: | 3, 10, 30 mg/kg | | Administration: | PO; once daily for 23 days (3 mg/kg; twice daily for 23 days) | | Result: | Ihibited tumor growth and induced BCL6 protein degradation. |
| [target]
BCL6 | [References]
[1] Sherman D. Abstract ND05: The discovery of ARV-393, a potent, orally bioavailable BCL6 targeting PROTAC? for the treatment of Non-Hodgkin’s Lymphoma[J]. Cancer Research, 2024, 84(7_Supplement): ND05-ND05.
[2] Paolo F. Caimi, et al. Phase 1 Study of ARV-393, a PROTAC BCL6 Degrader, in Advanced Non-Hodgkin Lymphoma. Blood. 2024, 144: 6505.
[3] Paolo Caimi, et al. Abstract PO-010: Trial in Progress: Phase 1 Study of ARV-393, a PROTAC BCL6 Degrader, in Advanced Non-Hodgkin Lymphoma. Blood Cancer Discov. 2024. 5 (3_Supplement): PO-010. |
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