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Bromodomain and extraterminal domain (BET) protein inhibitors are emerging as promising anticancer therapies. The gene encoding the E3 ubiquitin ligase substrate-binding adaptor speckle-type POZ protein (SPOP) is 2017-08-14 Because development of resistance to single targeted agents is common, we next performed sensitizer drug screens to identify potential combination therapies with the BET inhibitor CPI0610. Several PI3K or AKT inhibitors were among the top drug combinations identified and subsequent work showed CPI0610 synergized with alpelisib or MK2206 by inducing p53-independent apoptosis. Wu et al. identify an intrinsic mechanism that not only drives PI3K/AKT inhibitor resistance but also can be vulnerably targeted paradoxically by both BET and HDAC inhibitors.

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Image provided by Dr. Chris Kemp AKT protects Ewing sarcoma cells against BET inhibitors. A, TC32 and TC71 cells were treated with 10 nmol/L NHWD870 ± 100 nmol/L BMS754807 for 24 hours and subject to immunoblotting for indicated proteins. Actin was included as the loading control. Akt kinases, also known as PKB kinases are members of the AGC superfamily of serine/threonine protein kinases and have three isoforms (Akt1, Akt2 and Akt3). All isoforms have high structural similarity, possessing an N-terminal pleckstrin homology (PH) domain, a kinase domain and a C-terminal hydrophobic motif (HM). Combination studies showed synergistic interactions with dexamethasone, BH3 mimetics, and Akt pathway inhibitors. BET-specific PROTACs induced a rapid loss of viability of primary cells from myeloma patients, and delayed growth of MM1.S-based xenografts.

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Work through over 3,400 MRCGP (AKT) questions in SBA (Single Best Answer), EMQ (Extended Matching Question) and Free Text format Try questions from the Qbank now - no sign-up required!

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This website uses cookies so that we can provide you with the best user experience possible. Cookie information is stored in your browser and performs functions such as recognising you when you return to our website and helping our team to understand which sections of the website you find most interesting and useful. Many cellular processes in cancer are attributed to kinase signaling networks. V-akt murine thymoma viral oncogene homolog (AKT) plays a major role in the PI3K/AKT signaling pathways. AKT is activated by PI3K or phosphoinositide-dependent kinases (PDK) as well as growth factors, inflammation, and DNA damage. Signal transduction occurs through downstream effectors such as mTOR, glycogen Ayesha Akter-Best Online freelancer - Home | Facebook. Ayesha Akter-Best Online freelancer, Kishoreganj, Dhaka Division, Bangladesh.