Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTDP48B)

• DTT Name: Bromodomain-containing protein 2 (BRD2)
• Synonyms: Really interesting new gene 3 protein; RING3; O27.1.1; KIAA9001
• Gene Name: BRD2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Bromodomain
• UniProt ID: BRD2_HUMAN
• TTD ID: T86399
• Sequence:
  MLQNVTPHNKLPGEGNAGLLGLGPEAAAPGKRIRKPSLLYEGFESPTMASVPALQLTPAN
  PPPPEVSNPKKPGRVTNQLQYLHKVVMKALWKHQFAWPFRQPVDAVKLGLPDYHKIIKQP
  MDMGTIKRRLENNYYWAASECMQDFNTMFTNCYIYNKPTDDIVLMAQTLEKIFLQKVASM
  PQEEQELVVTIPKNSHKKGAKLAALQGSVTSAHQVPAVSSVSHTALYTPPPEIPTTVLNI
  PHPSVISSPLLKSLHSAGPPLLAVTAAPPAQPLAKKKGVKRKADTTTPTPTAILAPGSPA
  SPPGSLEPKAARLPPMRRESGRPIKPPRKDLPDSQQQHQSSKKGKLSEQLKHCNGILKEL
  LSKKHAAYAWPFYKPVDASALGLHDYHDIIKHPMDLSTVKRKMENRDYRDAQEFAADVRL
  MFSNCYKYNPPDHDVVAMARKLQDVFEFRYAKMPDEPLEPGPLPVSTAMPPGLAKSSSES
  SSEESSSESSSEEEEEEDEEDEEEEESESSDSEEERAHRLAELQEQLRAVHEQLAALSQG
  PISKPKRKREKKEKKKKRKAEKHRGRAGADEDDKGPRAPRPPQPKKSKKASGSGGGSAAL
  GPSGFGPSGGSGTKLPKKATKTAPPALPTGYDSEEEEESRPMSYDEKRQLSLDINKLPGE
  KLGRVVHIIQAREPSLRDSNPEEIEIDFETLKPSTLRELERYVLSCLRKKPRKPYTIKKP
  VGKTKEELALEKKRELEKRLQDVSGQLNSTKKPPKKANEKTESSSAQQVAVSRLSASSSS
  SDSSSSSSSSSSSDTSDSDSG
• Function: Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly. May play a role in spermatogenesis or folliculogenesis.
• Reactome Pathway: RUNX3 regulates p14-ARF (R-HSA-8951936)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
OTX-015	DMI8RG1	Acute myeloid leukaemia	2A60	Phase 1/2	[1]
ABBV-744	DMTEA9C	Acute myeloid leukaemia	2A60	Phase 1	[2]

6 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID26924192-Compound-102	DMEJ107	N. A.	N. A.	Patented	[3]
PMID26924192-Compound-103	DMWOCP7	N. A.	N. A.	Patented	[3]
PMID26924192-Compound-104	DM346EU	N. A.	N. A.	Patented	[3]
PMID26924192-Compound-105	DMAWLGI	N. A.	N. A.	Patented	[3]
PMID26924192-Compound-106	DM9HRZJ	N. A.	N. A.	Patented	[3]
Pyrrolo-pyrrolone derivative 1	DMN4SE5	N. A.	N. A.	Patented	[3]

9 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BIC1	DMFS2V9	Discovery agent	N.A.	Investigative	[4]
ET bromodomain inhibitor	DMH4MBW	Discovery agent	N.A.	Investigative	[5]
GW841819X	DMRL9IN	Discovery agent	N.A.	Investigative	[6]
I-BET151	DMYRUH2	Discovery agent	N.A.	Investigative	[7]
ME bromodomain inhibitor	DMMFYP9	Discovery agent	N.A.	Investigative	[5]
PMID21851057C4d	DMI1FGV	Discovery agent	N.A.	Investigative	[8]
PMID24000170C36	DMHUWZS	Discovery agent	N.A.	Investigative	[9]
PMID24000170C38	DMOLRIY	Discovery agent	N.A.	Investigative	[9]
XD14	DMUMACD	Discovery agent	N.A.	Investigative	[10]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Myelodysplastic syndrome	2C82	Bone marrow	6.53E-02	-0.05	-0.13

References

• [1] Targeting bromodomains: epigenetic readers of lysine acetylation.Nat Rev Drug Discov.2014 May;13(5):337-56.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] BET inhibitors in cancer therapeutics: a patent review.Expert Opin Ther Pat. 2016;26(4):505-22.
• [4] Real-time imaging of histone H4K12-specific acetylation determines the modes of action of histone deacetylase and bromodomain inhibitors. Chem Biol. 2011 Apr 22;18(4):495-507.
• [5] Chemical biology. A bump-and-hole approach to engineer controlled selectivity of BET bromodomain chemical probes. Science. 2014 Oct 31;346(6209):638-41.
• [6] Discovery and characterization of small molecule inhibitors of the BET family bromodomains. J Med Chem. 2011 Jun 9;54(11):3827-38.
• [7] Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature. 2011 Oct 2;478(7370):529-33.
• [8] 3,5-dimethylisoxazoles act as acetyl-lysine-mimetic bromodomain ligands. J Med Chem. 2011 Oct 13;54(19):6761-70.
• [9] Naphthyridines as novel BET family bromodomain inhibitors. ChemMedChem. 2014 Mar;9(3):580-9.
• [10] 4-Acyl pyrroles: mimicking acetylated lysines in histone code reading. Angew Chem Int Ed Engl. 2013 Dec 23;52(52):14055-9.