PROTAC BRD9 Degrader-12

PROTAC BRD9 Degrader-12 (compound B8) induces dose-dependent cooperative degradation of BRD9 and IKZF1 in MV4-11 cells, with DC₅₀ values of 57 pM and 62 pM for BRD9 and IKZF1, respectively. At 1 nM, it induces approximately 90% BRD9 degradation and nearly complete clearance of IKZF1, while no obvious GSPT1 degradation is observed^[1].
PROTAC BRD9 Degrader-12 (1 nM) initiates BRD9 degradation at approximately 4 h and achieves near-complete clearance at 12 h; IKZF1 degradation occurs more rapidly, with an approximately 50% reduction within 1 h and near-complete clearance at 4 h^[1].
PROTAC BRD9 Degrader-12-mediated degradation of BRD9 and IKZF1 is significantly inhibited by the proteasome inhibitor MG-132 or the NEDD8-activating enzyme inhibitor MLN4924. Competitive treatment with the BRD9 ligand I-BRD9 or the CRBN ligand pomalidomide similarly attenuates BRD9 degradation, indicating that this process depends on the formation of the BRD9/PROTAC/CRBN ternary complex, CRL-CRBN-dependent ubiquitination, and the proteasomal pathway^[1].
PROTAC BRD9 Degrader-12 does not induce significant degradation of BRD7 or BRD4 in MV4-11 cells. In quantitative proteomic analysis of OCI-ly1 cells, BRD9 and IKZF1 are identified as the major degraded proteins, while IKZF3 undergoes only moderate degradation. No obvious degradation of CK1α, GSPT1, IKZF2, and TP63 is detected, and multiple zinc finger proteins remain largely unaffected^[1].
PROTAC BRD9 Degrader-12 exerts a dose-dependent synergistic degradation effect on BRD9 and IKZF1 in RPMI-8226 and OCI-ly1 cells, with a maximum degradation level of approximately 99% at 1 nM^[1].
PROTAC BRD9 Degrader-12 (1-1000 nM; 24 h) dose-dependently increases the proportion of apoptotic cells detected by Annexin V/PI assay in MV4-11 cells, with the total apoptotic cell proportion rising to 24.9% at 1 μM^[1].
PROTAC BRD9 Degrader-12 (1-1000 nM; 24 h) alters the cell cycle distribution of MV4-11 cells in a dose-dependent manner, causing cell accumulation in the S phase accompanied by changes in the proportion of the G1 phase^[1].
PROTAC BRD9 Degrader-12 (7 days) exhibits broad antiproliferative activity against a variety of hematological malignancy cells, with IC₅₀ values of 0.2, 0.9, 0.1, and 0.5 nM in RS4;11, OCI-ly1, OCI-ly3, and OCI-ly10 cells, respectively, and IC₅₀ values all below 0.2 nM in SU-DHL-2, Granta-519, and Jeko-1 cells; its activity against the majority of tested solid tumor cells is generally weak^[1].
PROTAC BRD9 Degrader-12 (1-10 nM) only slightly reduces MYC mRNA in OCI-ly10 cells at 24 h, but significantly inhibits MYC transcription at 72 h, and concurrently suppresses the transcription of MYC-associated downstream genes CDC45, ORC2, SRPK1, CAD, and RRM1^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.