2851885-95-3CNC(=O)COc1cc2cc(Nc3nc(N4CCC(OC5CC(N6CCC(c7ccc8c(c7F)CN(C7CCC(=O)NC7=O)C8=O)CC6)C5)CC4)ncc3Cl)ccc2n(C(C)C)c1=OZOGOEUHUEFKKTD-UHFFFAOYSA-NZaloblideg is an orally bioavailable, targeted degrader composed of an E3 ubiquitin ligase-binding moiety that is conjugated, via a linker, to a B-cell lymphoma 6 protein (BCL6; BCL-6)-binding moiety using the proteolysis targeting chimera (PROTAC) technology, with potential antineoplastic activity. Upon oral administration of zaloblideg, the BCL6-binding moiety specifically targets and binds to BCL6 on tumor cells while the E3 ubiquitin ligase-binding moiety targets and binds to E3 ubiquitin ligase, thereby creating a ternary complex. This induces E3 ligase ubiquitination and proteasome-mediated degradation of BCL6. This prevents BCL6-mediated signaling and activation of downstream survival pathways. This leads to an inhibition of the growth of tumor cells that overexpress BCL6. BCL6, a transcriptional repressor overexpressed in certain tumor cells, serves an important role in cell signaling and tumor cell proliferation.
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BeschreibungARV-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.
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2851885-95-3CHEMBL6148050