BSJ-03-123

BSJ-03-123 is a selective PROTAC degrader of CDK6. BSJ-03-123 degrades CDK6, thereby inhibiting Rb S780 phosphorylation and inducing G1 phase arrest, while remodeling cell cycle and transcriptional signaling, with no effect on CDK4-dependent cancer cells. BSJ-03-123 reduces CDK6 protein levels in mouse ovarian tissues, increases the proportion of primordial follicles, and induces granulosa cell apoptosis, without impairing the ability of oocytes to resume meiosis and mature to the MII stage. BSJ-03-123 alleviates uveitis by blocking the HDACs-CDK6/ID2 axis. BSJ-03-123 can be used in studies related to acute myeloid leukemia, mantle cell lymphoma and autoimmune uveitis^[1][2][3]. IC50 & Target:CDK6, PROTAC^[1] In Vitro:BSJ-03-123 (50-1000 nM; 30 min-4 h) induces CRBN-dependent, concentration- and time-dependent, paralog-selective degradation of CDK6 (but not CDK4) in cultured cells, with comparable binding affinity for the cellular targets of CDK4 and CDK6^[1].
BSJ-03-123 (100 nM; 2 h) exhibits genome-wide proteome selectivity for CDK6 degradation in MOLT4 cells^[1].
BSJ-03-123 (200-1000 nM; 8-12 days, treatment refreshed every 2 days) selectively inhibits the proliferation of CDK6-dependent AML cell lines (MV4-11, MOLM13, P31/FUJ) without affecting CDK4-dependent cell lines^[1].
BSJ-03-123 (200 nM; 24 h) induces G1-phase cell cycle arrest in MV4-11 and MOLM13 acute myeloid leukemia (AML) cells without increasing apoptosis^[1].
BSJ-03-123 (200 nM; 2 h) aberrantly regulates the phosphorylation levels of 197 peptides in MV4-11 cells. Its regulatory targets are enriched in CDK motifs, and both known and novel CDK6 substrates are identified^[1].
BSJ-03-123 (200 nM; 6 h) induces transcriptional changes in MV4-11 cells, which are highly correlated with those induced by palbociclib, affecting pathways including cell cycle regulation, DNA replication and chromatin organization^[1].
BSJ-03-123 (0.1-5 μM; 4 h) induces CRBN-dependent selective degradation of CDK6 in wild-type Jurkat cells, with no such effect on CDK4, IKZF1 or IKZF3^[2].
BSJ-03-123 (250 nM; 5 h) selectively degrades CDK6 in Molt4 cells without reducing the levels of CDK4, IKZF1 or IKZF3^[2].
BSJ-03-123 (500 nM-2 μM; 10 min) selectively induces the formation of a ternary complex between CDK6 and CRBN in CRBN-deficient HEK293T cells (but fails to induce such a complex between CDK4 and CRBN), while pretreatment with Palbociclib (HY-50767) or lenalidomide (HY-A0003) blocks the formation of this complex^[1].
BSJ-03-123 (200 nM; 8-24 h) reduces the phosphorylation level of Rb at the S780 site in cultured cells in a CRBN-dependent manner, with an effect comparable to that of CDK4/6 inhibitors^[1].
BSJ-03-123 (3 μM; 72 h) regulates CD4+ effector T cell-mediated immune responses in human peripheral blood mononuclear cells (PBMCs), and supports the modulation of Th17/Treg balance associated with the pathogenesis of autoimmune uveitis^[3].
BSJ-03-123 (3 μM; 72 h) regulates IRBP-stimulated CD4⁺ T cell activity, including Th17 cell differentiation, in mouse CDLN cells^[3]. In Vivo:BSJ-03-123 (50 mg/kg; i.p.; daily; 13 days) effectively alleviates experimental autoimmune uveitis by reducing retinal inflammation, restoring Th17/Treg balance, and suppressing pathogenic Th17 cell activity^[3].