Target Information

Target General Infomation
Target ID
T40556
Former ID
TTDI02032
Target Name
Bromodomain-containing protein 4
Gene Name
BRD4
Synonyms
Protein HUNK1; BRD4
Target Type
Clinical Trial
Disease Alzheimer disease; Atherosclerosis [ICD9:331, 414.0, 440; ICD10: G30, I70]
Advanced solid tumor [ICD9: 140-199; ICD10: C00-C75, C7A, C7B]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Myelodysplastic syndrome [ICD9: 238.7; ICD10: D46]
Function
Isoform B: Acts asa chromatin insulator in the DNA damage response pathway. Inhibits DNA damage response signaling by recruiting the condensin-2 complex to acetylated histones, leading to chromatin structure remodeling, insulating the region from DNA damage response by limiting spreading of histone H2AFX/H2A.x phosphorylation.
BioChemical Class
Bromodomain
UniProt ID
O60885
Sequence
MSAESGPGTRLRNLPVMGDGLETSQMSTTQAQAQPQPANAASTNPPPPETSNPNKPKRQT
NQLQYLLRVVLKTLWKHQFAWPFQQPVDAVKLNLPDYYKIIKTPMDMGTIKKRLENNYYW
NAQECIQDFNTMFTNCYIYNKPGDDIVLMAEALEKLFLQKINELPTEETEIMIVQAKGRG
RGRKETGTAKPGVSTVPNTTQASTPPQTQTPQPNPPPVQATPHPFPAVTPDLIVQTPVMT
VVPPQPLQTPPPVPPQPQPPPAPAPQPVQSHPPIIAATPQPVKTKKGVKRKADTTTPTTI
DPIHEPPSLPPEPKTTKLGQRRESSRPVKPPKKDVPDSQQHPAPEKSSKVSEQLKCCSGI
LKEMFAKKHAAYAWPFYKPVDVEALGLHDYCDIIKHPMDMSTIKSKLEAREYRDAQEFGA
DVRLMFSNCYKYNPPDHEVVAMARKLQDVFEMRFAKMPDEPEEPVVAVSSPAVPPPTKVV
APPSSSDSSSDSSSDSDSSTDDSEEERAQRLAELQEQLKAVHEQLAALSQPQQNKPKKKE
KDKKEKKKEKHKRKEEVEENKKSKAKEPPPKKTKKNNSSNSNVSKKEPAPMKSKPPPTYE
SEEEDKCKPMSYEEKRQLSLDINKLPGEKLGRVVHIIQSREPSLKNSNPDEIEIDFETLK
PSTLRELERYVTSCLRKKRKPQAEKVDVIAGSSKMKGFSSSESESSSESSSSDSEDSETE
MAPKSKKKGHPGREQKKHHHHHHQQMQQAPAPVPQQPPPPPQQPPPPPPPQQQQQPPPPP
PPPSMPQQAAPAMKSSPPPFIATQVPVLEPQLPGSVFDPIGHFTQPILHLPQPELPPHLP
QPPEHSTPPHLNQHAVVSPPALHNALPQQPSRPSNRAAALPPKPARPPAVSPALTQTPLL
PQPPMAQPPQVLLEDEEPPAPPLTSMQMQLYLQQLQKVQPPTPLLPSVKVQSQPPPPLPP
PPHPSVQQQLQQQPPPPPPPQPQPPPQQQHQPPPRPVHLQPMQFSTHIQQPPPPQGQQPP
HPPPGQQPPPPQPAKPQQVIQHHHSPRHHKSDPYSTGHLREAPSPLMIHSPQMSQFQSLT
HQSPPQQNVQPKKQELRAASVVQPQPLVVVKEEKIHSPIIRSEPFSPSLRPEPPKHPESI
KAPVHLPQRPEMKPVDVGRPVIRPPEQNAPPPGAPDKDKQKQEPKTPVAPKKDLKIKNMG
SWASLVQKHPTTPSSTAKSSSDSFEQFRRAAREKEEREKALKAQAEHAEKEKERLRQERM
RSREDEDALEQARRAHEEARRRQEQQQQQRQEQQQQQQQQAAAVAAAATPQAQSSQPQSM
LDQQRELARKREQERRRREAMAATIDMNFQSDLLSIFEENLF
Drugs and Mode of Action
Drug(s) RVX-208 Drug Info Phase 1/2 Alzheimer disease; Atherosclerosis [522457], [542052]
CPI-0610 Drug Info Phase 1 Myelodysplastic syndrome [531179], [531260]
GSK525762 Drug Info Phase 1 Cancer [531179], [531260], [542051]
OTX-015 Drug Info Phase 1 Myelodysplastic syndrome [531179], [531260], [543085]
TEN-010 Drug Info Phase 1 Advanced solid tumor [525017]
Inhibitor (+)-JQ1 Drug Info [531179]
BzT-7 Drug Info [531726]
compound 1 Drug Info [533036]
compound 15 (Hay et al., 2013) Drug Info [543526]
compound 2 Drug Info [533036]
compound 3 Drug Info [533036]
compound 36 Drug Info [532467]
compound 38 Drug Info [532467]
compound 4d Drug Info [531602]
compound 7d Drug Info [533146]
compound 9 Drug Info [532277]
CPI-203 Drug Info [531875]
GW841819X Drug Info [531473]
I-BET151 Drug Info [531641]
isoxazole azepine compound 3 Drug Info [532827]
MS417 Drug Info [531928]
MS436 Drug Info [532517]
PFI-1 Drug Info [532093]
XD1 Drug Info [532562]
XD14 Drug Info [532562]
Modulator CPI-0610 Drug Info [531179], [531260]
GSK525762 Drug Info
OTX-015 Drug Info
RVX-208 Drug Info
TEN-010 Drug Info
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
WikiPathways Chemical Compounds to monitor Proteins
References
Ref 522457ClinicalTrials.gov (NCT00768274) Safety, Pharmacokinetic Study of RVX000222 in Healthy Subjects and Subjects With Low HDL Cholesterol. U.S. National Institutes of Health.
Ref 525017ClinicalTrials.gov (NCT02308761) A Dose Escalation and Cohort Expansion Study of TEN-010 in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndrome. U.S. National Institutes of Health.
Ref 531179Selective inhibition of BET bromodomains. Nature. 2010 Dec 23;468(7327):1067-73.
Ref 531260Suppression of inflammation by a synthetic histone mimic. Nature. 2010 Dec 23;468(7327):1119-23.
Ref 542051(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7033).
Ref 542052(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7034).
Ref 543085(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8359).
Ref 531179Selective inhibition of BET bromodomains. Nature. 2010 Dec 23;468(7327):1067-73.
Ref 531260Suppression of inflammation by a synthetic histone mimic. Nature. 2010 Dec 23;468(7327):1119-23.
Ref 531473Discovery and characterization of small molecule inhibitors of the BET family bromodomains. J Med Chem. 2011 Jun 9;54(11):3827-38.
Ref 5316023,5-dimethylisoxazoles act as acetyl-lysine-mimetic bromodomain ligands. J Med Chem. 2011 Oct 13;54(19):6761-70.
Ref 531641Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature. 2011 Oct 2;478(7370):529-33.
Ref 531726Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family. Bioorg Med Chem. 2012 Mar 15;20(6):1878-86.
Ref 531875BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. Proc Natl Acad Sci U S A. 2012 May 1;109(18):6927-32.
Ref 531928Down-regulation of NF-?B transcriptional activity in HIV-associated kidney disease by BRD4 inhibition. J Biol Chem. 2012 Aug 17;287(34):28840-51.
Ref 532093Identification of a chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization of a fragment-derived hit. J Med Chem. 2012 Nov 26;55(22):9831-7.
Ref 532277Optimization of 3,5-dimethylisoxazole derivatives as potent bromodomain ligands. J Med Chem. 2013 Apr 25;56(8):3217-27.
Ref 532467Naphthyridines as novel BET family bromodomain inhibitors. ChemMedChem. 2014 Mar;9(3):580-9.
Ref 532517Structure-guided design of potent diazobenzene inhibitors for the BET bromodomains. J Med Chem. 2013 Nov 27;56(22):9251-64.
Ref 5325624-Acyl pyrroles: mimicking acetylated lysines in histone code reading. Angew Chem Int Ed Engl. 2013 Dec 23;52(52):14055-9.
Ref 532827Discovery, Design, and Optimization of Isoxazole Azepine BET Inhibitors. ACS Med Chem Lett. 2013 Jul 16;4(9):835-40.
Ref 5330361,3-Dimethyl Benzimidazolones Are Potent, Selective Inhibitors of the BRPF1 Bromodomain. ACS Med Chem Lett. 2014 Sep 10;5(11):1190-5.
Ref 5331469H-purine scaffold reveals induced-fit pocket plasticity of the BRD9 bromodomain. J Med Chem. 2015 Mar 26;58(6):2718-36.
Ref 543526(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1945).

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.