In biochemical assays, H5 shows IC50 = 7.9 ± 0.5 nM, outperforming JQ-1 (IC50 = 33.0 ± 1.0 nM) by 4-fold...In the HCT-116 xenograft mouse model, oral administration of H5 suppressed tumor growth (TGI = 82 % at 50 mg/kg) and downregulated the BRD4-driven oncoproteins c-MYC and BCL-2. Collectively, H5 emerges as a highly promising BRD4-targeted candidate for colorectal cancer treatment.

P1, N=3, Not yet recruiting, Novartis Pharmaceuticals

P1, N=24, Not yet recruiting, Novartis Pharmaceuticals

P1, N=41, Completed, Jacobio Pharmaceuticals Co., Ltd. | Recruiting --> Completed | N=30 --> 41

To investigate whether MDM2 can serve as tumor-specific PROTAC E3 in certain setting, we analyzed the benchmark compound A1874 (JQ1-Idasanutlin chimera targeting BRD4) under various conditions that affect MDM2 expression and activity. Importantly, A1874 showed on average ~12-fold higher potency in tumor cells with MDM2 amplification compared to non-amplified cells, correlating with enhanced cytotoxicity. The results suggest that tumors with MDM2 amplification or overexpression can be selectively targeted using PROTAC approach.

P1/2, N=152, Recruiting, Jacobio Pharmaceuticals Co., Ltd. | Trial completion date: Sep 2024 --> Jul 2028 | Trial primary completion date: Jan 2024 --> Jan 2028

P1/2, N=36, Recruiting, National Cancer Institute (NCI) | Phase classification: P1 --> P1/2

P1/2, N=49, Recruiting, National Cancer Institute (NCI) | N=30 --> 49

Moreover, pharmacogenomic analyses revealed that CHOP upregulation correlates with increased sensitivity to several agents, and molecular docking highlighted Irinotecan and JQ1 as potential synergistic partners with TCPC. Collectively, this work demonstrates that nanomedicine guided by omics can couple organelle-specific delivery with ER-stress amplification to achieve potent antitumor efficacy. Overall, this work establishes an omics-guided materials strategy that integrates organelle-targeted delivery with ER-stress amplification for effective melanoma therapy.

To investigate the biological effects of BET proteins, two small-molecule inhibitors, JQ1 and I-BET762, were used to assess their impact on UF cell behavior and transcriptomic profiles. Collectively, these results support that BET proteins play a pivotal role in regulating key signaling pathways and cellular processes in UFs. Targeting BET proteins may therefore represent a promising non-hormonal therapeutic strategy for UF treatment.

In vivo, JQ1-icluster suppresses tumor growth with high specificity and retention. This work presents a promising multi-responsive nanoplatform capable of precise delivery and deep penetration.

Current cancer treatments, such as chemotherapy and targeted therapies like JQ1, frequently come with side effects and toxicity, which highlights the need for safer alternatives...For Calyxins A, the binding free energy was -72.53 kcal/mol with a docking score of -10.132 kcal/mol, while for Deoxycalyxin A, it was -73.03 kcal/mol with a docking score of -10.162 kcal/mol. Our research indicates that these natural compounds, Calyxins C, Calyxins A, and Deoxyocalyxin A, exhibit higher stability and favorable interaction profiles, which could be effective and less toxic drug leads for leukemia treatment, paving the way for future experimental validation and clinical studies.