P1, N=24, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

Importantly, in vivo studies using a xenograft mouse model demonstrate significant tumor growth inhibition, with the nanoformulation + NIR irradiated group showing the most effective anti-tumor outcome with negligible hepatic, renal, and cardiac toxicities. Taken together, it may be stated that the doxorubicin/JQ1 co-loaded PBNCs might be a potential next-generation anti-TNBC theranostic agent, which combines dual-mode MRI capability and combination therapy with reduced side effects.

In addition, we demonstrate that the first bromodomain of the bromodomain and extraterminal domain-containing protein BRD4 binds to the acetylated region of interest and that this interaction is inhibited through the bromodomain and extraterminal domain inhibitor JQ1. These findings confer molecular mechanistic detail to previous observations that BRD4 and PAX3-FOXO1 colocalize at superenhancers in ARMS, adding to the growing body of literature exploring how BRD4 contacts cancer-relevant transcription factors in ways potentially relevant to the use of bromodomain and extraterminal domain inhibitors in cancer treatment.

P1, N=65, Recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2026 --> Jun 2027 | Trial primary completion date: Apr 2026 --> Jun 2027

P1, N=45, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2026 --> Jun 2027

P1, N=30, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2026 --> Jun 2027

Proteomic analysis identified unique protein candidates altered in MZ-1- and SIM-1-treated KSHV-infected immortalized endothelial cells compared with (+)-JQ1-treated cells. In summary, our study develops an effective strategy against KSHV-infected immortalized endothelial cells using selective BRD PROTACs, which may help improve therapeutic outcomes for KSHV-related malignancies in the future.

P2/3, N=60, Not yet recruiting, Novartis Pharma AG

JQ1 conveniently entered the adjacent cell nucleus and prevented induced PD-L1 production at the transcriptional level...Besides degrading PD-L1, the cholesterol metabolism regulation of AVA could also downregulate integrin αV expression to inhibit tumor metastasis. Therefore, by improving immunogenicity, eliminating immune resistance, and downregulating integrin αV, these synergistic therapeutic strategies efficiently inhibit primary tumor and pulmonary metastasis in orthotopic TNBC.

Concurrently, the degradable MN tip enables sustained release of JQ1, which enhances OA replication, modulates lactic acid levels and PD-L1 expression, thereby reprogramming the immunosuppressive TME to promote T-cell infiltration and cytotoxicity. In murine models, MN-OJ demonstrated potent inhibition of both primary and distal tumors, without systemic toxicity. This innovative platform combines immediate tumor destruction with sustained immune modulation, offering a promising clinical approach for melanoma therapy.

SHP2 overexpression, SHP2 knockdown, and SP1 inhibitor BDR4 inhibitor JQ-1 were used to examine the effects of SHP2, SP1, and BRD4 on macrophage polarization and cancer cell death, migration, and invasion...Additionally, there was an increase in cancer cell invasion, migration, and death. SHP2 in TAMs promotes gastric adenocarcinoma survival by inhibiting P38/ erk1 /SP1/BRD4/STING-induced inflammation and ROS.

CZL-149 displays favorable drug-like properties and metabolic profile, achieving 107% oral bioavailability in mice. Importantly, CZL-149 outperformed NEO2734 in both antitumor efficacy (TGI = 78%) and safety in vivo, highlighting its potential as an advanced preclinical candidate worthy of further development.