Table 2 BRD4 BD2 bromodomain selective inhibitors, PROTAC BRD4 protein degraders, and dual BRD4 and CBP/p300 bromodomain co-inhibitors.
From: Super-enhancers and the super-enhancer reader BRD4: tumorigenic factors and therapeutic targets
Targets | Compound | Structure | Functions | References |
|---|---|---|---|---|
BD2 bromodomain selective inhibitor | ABBV-744 |
| Induces anticancer effects against acute myeloid leukemia and prostate cancer in vitro and in mouse models with better toxicity profile than BD1 and BD2 bromodomain inhibitors | [55] |
BD2 bromodomain selective inhibitor | GSK620 |
| Suppresses inflammatory disease in preclinical models | [58] |
PROTAC BRD4 protein degrader | ARV-771 |
| Reduces castration-resistant prostate cancer cell proliferation and survival in vitro, and results in tumor regression in mice. | [60] |
PROTAC BRD4 protein degrader | A1874 |
| Combines JQ1 and the MDM2 antagonist idasanutlin activities, degrades BRD4 protein by 98% and stabilizes p53 protein. Reduces cancer cell proliferation and survival. | [61] |
BRD4 and CBP/p300 bromodomain co-inhibitor | XP-524 |
| Shows anticancer efficacy comparable to combination therapy with the BRD4 inhibitor JQ-1 and the CBP/p300 inhibitor SGC-CBP30 in pancreatic ductal adenocarcinoma cells. | [62] |
BRD4 and CBP/p300 bromodomain co-inhibitor | NEO2734 |
| Show more potent anticancer effects than single-agent BRD4 or CBP/p300 inhibitors alone. Induces colorectal cancer, leukemia and lymphoma cell apoptosis in vitro and in mouse models. |
