In this study, EZH2 levels were modulated by CRISPR/Cas9 gene editing and PRC2 activity was inhibited with EZH2 inhibitor EPZ6438 or EED inhibitor MAK683. This was accompanied by increased expression of other PcG genes, including EZH1, CBX2, RING1, EED, and SUZ12, suggesting a compensatory interaction between PRC2 and PRC1 complexes. These findings provide significant clinical relevance, both in elucidating the mechanisms of novel molecular targets and in guiding treatment strategies for lung cancer when using epigenetic inhibitors.

P1, N=105, Recruiting, Ascentage Pharma Group Inc. | Trial completion date: Mar 2026 --> Jul 2028 | Trial primary completion date: Aug 2025 --> Dec 2027

P1, N=139, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; The decision of early termination was made due to business reasons, and was not based on any safety or tolerability concerns for MAK683

Furthermore, the combination of the PPARγ agonist rosiglitazone and the PRC2 inhibitor MAK683 exhibited a higher inhibition on Ki67 positivity in tumor xenograft compared to MAK683 alone. High CEBPA, PLIN1 and FABP4 levels positively correlated with favorable prognosis in sarcoma patients in TCGA cohort. Together, these findings unveil an epigenetic regulatory mechanism for PPARG and highlight the essential role of PPARγ and C/EBPα in the adipocyte differentiation of MRTs and sarcomas with a potential clinical implication.

P1/2, N=191, Active, not recruiting, Shanghai Blueray Biopharma Co., Ltd. | Not yet recruiting --> Active, not recruiting

P1, N=139, Active, not recruiting, Novartis Pharmaceuticals | Phase classification: P1/2 --> P1

76-fold of the control group, respectively, which was pharmacologically superior to effects observed with hydroxyurea at 33 µM (~6. APG-5918 also showed synergistic antianemia effects when combined with EPO. These findings support APG-5918 as a novel treatment option for CKD-induced anemia.

These findings demonstrate that inhibition of EED through FTX-6058 leads to a minimal, transient impact on the bone marrow in mice, and any transcriptional changes are rapidly reversible following cessation of dosing. A small molecule EED inhibitor has the potential to provide a new treatment for sickle cell disease without irreversibly altering the bone marrow.

Our findings provided the first preclinical evidence supporting nicardipine as a novel EED inhibitor that has the potential to be promptly tested in PCa patients to overcome chemoresistance and improve clinical outcomes.

Characterization of UNC7700 and related compounds for ternary complex formation and cellular permeability to provide a rationale for the observed improvement in degradation efficiency remained challenging. Importantly, UNC7700 dramatically reduces H3K27me3 levels and is anti-proliferative in DB cells (EC = 0.79 ± 0.53 μM).