PROTAC BCL6 Degrader-2 is an orally active, selective BCL6 PROTAC degrader ( DC50: 0.45 nM in HEK293T cells). PROTAC BCL6 Degrader-2 promotes ubiquitination and degradation of BCL6. It exhibits anticancer activity against BCL6-dependent diffuse large B-cell lymphoma. PROTAC BCL6 Degrader-2 can be used for the research of diffuse large B-cell lymphoma [1]. (Pink: BCL6 ligand; Blue: Cereblon ligand; Black: linker).
In Vivo, PROTAC BCL6 Degrader-2 (50 mg/kg; p.o.; daily; 17 days) achieves 37.2% tumor growth inhibition and reduces BCL6 protein levels in OCI-LY1 DLBCL xenografts in NOD-SCID mice without obvious toxicity[1].
In Vitro, PROTAC BCL6 Degrader-2 (Compound A19) (0.001-100 nM; 24 h) potently degrades BCL6 in HEK293T cells stably expressing BCL6-GFP, with a DC50 of 0.45 nM and a maximum degradation rate of up to 94.60% at a concentration of 100 nM[1]. PROTAC BCL6 Degrader-2 (0.001-100 nM; 0-24 h) potently and rapidly degrades BCL6 in OCI-LY1 diffuse large B-cell lymphoma (DLBCL) cells, with a DC50 of 0.034 nM, a maximum degradation rate of >99% at 24 h, and complete degradation achieved within 1 h at a concentration of 40 nM[1]. PROTAC BCL6 Degrader-2 (10 nM; 6 h) selectively degrades BCL6 in OCI-LY1 diffuse large B-cell lymphoma (DLBCL) cells, with no effect on the novel CRBN substrates IKZF1, IKZF2, IKZF3 or GSPT1[1]. PROTAC BCL6 Degrader-2 (7 days) potently inhibits the proliferation of OCI-LY1 diffuse large B-cell lymphoma (DLBCL) cells, with an IC50 value of 12.78 nM[1]. PROTAC BCL6 Degrader-2 (7 days) inhibits the growth of BCL6-dependent HT, SU-DHL4 and OCI-LY10 diffuse large B-cell lymphoma (DLBCL) cells, with corresponding IC50 values of 36.30 nM, 500.00 nM and 835.33 nM, but shows no activity in BCL6-independent Toledo DLBCL cells[1].
References:
[1]. Yu X, et al. Discovery of a Selective and Potent BCL6 PROTAC with Efficacious Antiproliferative Activity for the Treatment of Diffuse Large B-Cell Lymphoma. Journal of medicinal chemistry. 2025 Oct 09;68(19):20180-20206.
In Vivo, PROTAC BCL6 Degrader-2 (50 mg/kg; p.o.; daily; 17 days) achieves 37.2% tumor growth inhibition and reduces BCL6 protein levels in OCI-LY1 DLBCL xenografts in NOD-SCID mice without obvious toxicity[1].
In Vitro, PROTAC BCL6 Degrader-2 (Compound A19) (0.001-100 nM; 24 h) potently degrades BCL6 in HEK293T cells stably expressing BCL6-GFP, with a DC50 of 0.45 nM and a maximum degradation rate of up to 94.60% at a concentration of 100 nM[1]. PROTAC BCL6 Degrader-2 (0.001-100 nM; 0-24 h) potently and rapidly degrades BCL6 in OCI-LY1 diffuse large B-cell lymphoma (DLBCL) cells, with a DC50 of 0.034 nM, a maximum degradation rate of >99% at 24 h, and complete degradation achieved within 1 h at a concentration of 40 nM[1]. PROTAC BCL6 Degrader-2 (10 nM; 6 h) selectively degrades BCL6 in OCI-LY1 diffuse large B-cell lymphoma (DLBCL) cells, with no effect on the novel CRBN substrates IKZF1, IKZF2, IKZF3 or GSPT1[1]. PROTAC BCL6 Degrader-2 (7 days) potently inhibits the proliferation of OCI-LY1 diffuse large B-cell lymphoma (DLBCL) cells, with an IC50 value of 12.78 nM[1]. PROTAC BCL6 Degrader-2 (7 days) inhibits the growth of BCL6-dependent HT, SU-DHL4 and OCI-LY10 diffuse large B-cell lymphoma (DLBCL) cells, with corresponding IC50 values of 36.30 nM, 500.00 nM and 835.33 nM, but shows no activity in BCL6-independent Toledo DLBCL cells[1].
References:
[1]. Yu X, et al. Discovery of a Selective and Potent BCL6 PROTAC with Efficacious Antiproliferative Activity for the Treatment of Diffuse Large B-Cell Lymphoma. Journal of medicinal chemistry. 2025 Oct 09;68(19):20180-20206.