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.

We establish NNMT as a central metabolic-immune hub that orchestrates TGF-β-mediated CD8⁺ T cell dysfunction and endothelial reprogramming in ccRCC.

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

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

Specifically, the c-Myc inhibitor JQ1 and bovine serum albumin (BSA)-decorated nanoparticles loaded with the actin cytoskeleton inhibitor NP-G2-044 (BPG) were encapsulated into a reactive oxygen species (ROS)-sensitive hydrogel (JQ1 + BPG@gel). This hydrogel system improved the anti-recurrence efficacy of CAR-T therapy by 9-fold compared with monotherapy while establishing durable immune surveillance via memory T-cell differentiation within lymphoid organs. This research offers an innovative strategy to improve postoperative tumor cure rates and potentiate CAR-T immunotherapy.

P1/2, N=216, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: May 2026 --> Aug 2028 | Trial primary completion date: May 2026 --> Aug 2028

P1, N=30, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended