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Dual-target inhibitors of bromodomain-containing protein 4 (BRD4) in cancer therapy: Current situation and future directions
Institution:State Key Laboratory of Biotherapy and Cancer Center and Department of Otolaryngology, Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
Abstract:Bromodomain-containing protein 4 (BRD4) is emerging as a therapeutic target that acts synergistically with other targets of small-molecule drugs in cancer. Therefore, the discovery of potential new dual-target inhibitors of BRD4 may be a promising strategy for cancer therapy. In this review, we highlight a series of strategies to design therapeutic dual-target inhibitors of BRD4 that focus on the synergistic functions of this protein. Drug combinations that exploit synthetic lethality, protein–protein interactions, functional complementarity, and blocking of resistance mechanisms could ultimately overcome the barriers inherent to the development of BRD4 inhibitors as future cancer drugs.
Keywords:Bromodomain-containing protein 4 (BRD4)  Cancer therapy  Small-molecule drug  Dual-target inhibitor  Designing strategy  ALK"}  {"#name":"keyword"  "$":{"id":"k0035"}  "$$":[{"#name":"text"  "_":"anaplastic lymphoma kinase  AML"}  {"#name":"keyword"  "$":{"id":"k0045"}  "$$":[{"#name":"text"  "_":"acute myeloid leukemia  AMPK"}  {"#name":"keyword"  "$":{"id":"k0055"}  "$$":[{"#name":"text"  "_":"AMP-activated protein kinase  AR"}  {"#name":"keyword"  "$":{"id":"k0065"}  "$$":[{"#name":"text"  "_":"androgen receptor  AURKA"}  {"#name":"keyword"  "$":{"id":"k0075"}  "$$":[{"#name":"text"  "_":"aurora kinase A  BET"}  {"#name":"keyword"  "$":{"id":"k0085"}  "$$":[{"#name":"text"  "_":"bromodomain and extraterminal  BRD4"}  {"#name":"keyword"  "$":{"id":"k0095"}  "$$":[{"#name":"text"  "_":"Bromodomain-containing protein 4  CDK"}  {"#name":"keyword"  "$":{"id":"k0105"}  "$$":[{"#name":"text"  "_":"cyclin-dependent kinase  CRPC"}  {"#name":"keyword"  "$":{"id":"k0115"}  "$$":[{"#name":"text"  "_":"castration-resistant prostate cancer  EGFR"}  {"#name":"keyword"  "$":{"id":"k0125"}  "$$":[{"#name":"text"  "_":"epidermal growth factor receptor  HDAC"}  {"#name":"keyword"  "$":{"id":"k0135"}  "$$":[{"#name":"text"  "_":"histone deacetylase  PARP"}  {"#name":"keyword"  "$":{"id":"k0145"}  "$$":[{"#name":"text"  "_":"poly(ADP-ribose) polymerase  PI3K"}  {"#name":"keyword"  "$":{"id":"k0155"}  "$$":[{"#name":"text"  "_":"phosphatidylinositol 3-kinase  PLK1"}  {"#name":"keyword"  "$":{"id":"k0165"}  "$$":[{"#name":"text"  "_":"polo-like kinase 1  PPI"}  {"#name":"keyword"  "$":{"id":"k0175"}  "$$":[{"#name":"text"  "_":"protein-protein interaction  PROTAC"}  {"#name":"keyword"  "$":{"id":"k0185"}  "$$":[{"#name":"text"  "_":"proteolysis-targeting chimera  SE"}  {"#name":"keyword"  "$":{"id":"k0195"}  "$$":[{"#name":"text"  "_":"super-enhancer region
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