ARV-393

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

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.