Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQAWWO1)

• DOT Name: B-cell lymphoma 6 protein (BCL6)
• Synonyms: BCL-6; B-cell lymphoma 5 protein; BCL-5; Protein LAZ-3; Zinc finger and BTB domain-containing protein 27; Zinc finger protein 51
• Gene Name: BCL6
• UniProt ID: BCL6_HUMAN
• PDB ID: 1R28 ; 1R29 ; 1R2B ; 2EN2 ; 2EOS ; 2LCE ; 2YRM ; 3BIM ; 3E4U ; 3LBZ ; 4CP3 ; 4U2M ; 5H7G ; 5H7H ; 5MW2 ; 5MW6 ; 5MWD ; 5N1X ; 5N1Z ; 5N20 ; 5N21 ; 5X4M ; 5X4N ; 5X4O ; 5X4P ; 5X4Q ; 5X9O ; 5X9P ; 6C3L ; 6C3N ; 6CQ1 ; 6EW6 ; 6EW7 ; 6EW8 ; 6TBT ; 6TCJ ; 6TOF ; 6TOG ; 6TOH ; 6TOI ; 6TOJ ; 6TOK ; 6TOL ; 6TOM ; 6TON ; 6TOO ; 6XMX ; 6XWF ; 6XXS ; 6XYX ; 6XZZ ; 6Y17 ; 6ZBU ; 7BDE ; 7LWE ; 7LWF ; 7LWG ; 7LZQ ; 7LZR ; 7LZS ; 7OKD ; 7OKE ; 7OKF ; 7OKG ; 7OKH ; 7OKI ; 7OKJ ; 7OKK ; 7OKL ; 7OKM ; 7Q7R ; 7Q7S ; 7Q7T ; 7Q7U ; 7Q7V ; 7QK0 ; 7RUW ; 7RUX ; 7RUY ; 7RUZ ; 7RV0 ; 7RV1 ; 7RV2 ; 7RV3 ; 7RV4 ; 7RV5 ; 7RV6 ; 7RV7 ; 7RV8 ; 7RV9 ; 7T0S ; 7T0T ; 7T0U ; 7ZWN ; 7ZWO ; 7ZWP ; 7ZWQ ; 7ZWR ; 7ZWS ; 7ZWT ; 7ZWU ; 7ZWV ; 7ZWW ; 7ZWX ; 7ZWY ; 7ZWZ ; 8AS9 ; 8C78
• Pfam ID: PF00651 ; PF00096
• Sequence:
  MASPADSCIQFTRHASDVLLNLNRLRSRDILTDVVIVVSREQFRAHKTVLMACSGLFYSI
  FTDQLKCNLSVINLDPEINPEGFCILLDFMYTSRLNLREGNIMAVMATAMYLQMEHVVDT
  CRKFIKASEAEMVSAIKPPREEFLNSRMLMPQDIMAYRGREVVENNLPLRSAPGCESRAF
  APSLYSGLSTPPASYSMYSHLPVSSLLFSDEEFRDVRMPVANPFPKERALPCDSARPVPG
  EYSRPTLEVSPNVCHSNIYSPKETIPEEARSDMHYSVAEGLKPAAPSARNAPYFPCDKAS
  KEEERPSSEDEIALHFEPPNAPLNRKGLVSPQSPQKSDCQPNSPTESCSSKNACILQASG
  SPPAKSPTDPKACNWKKYKFIVLNSLNQNAKPEGPEQAELGRLSPRAYTAPPACQPPMEP
  ENLDLQSPTKLSASGEDSTIPQASRLNNIVNRSMTGSPRSSSESHSPLYMHPPKCTSCGS
  QSPQHAEMCLHTAGPTFPEEMGETQSEYSDSSCENGAFFCNECDCRFSEEASLKRHTLQT
  HSDKPYKCDRCQASFRYKGNLASHKTVHTGEKPYRCNICGAQFNRPANLKTHTRIHSGEK
  PYKCETCGARFVQVAHLRAHVLIHTGEKPYPCEICGTRFRHLQTLKSHLRIHTGEKPYHC
  EKCNLHFRHKSQLRLHLRQKHGAITNTKVQYRVSATDLPPELPKAC
• Function: Transcriptional repressor mainly required for germinal center (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions. Forms complexes with different corepressors and histone deacetylases to repress the transcriptional expression of different subsets of target genes. Represses its target genes by binding directly to the DNA sequence 5'-TTCCTAGAA-3' (BCL6-binding site) or indirectly by repressing the transcriptional activity of transcription factors. In GC B-cells, represses genes that function in differentiation, inflammation, apoptosis and cell cycle control, also autoregulates its transcriptional expression and up-regulates, indirectly, the expression of some genes important for GC reactions, such as AICDA, through the repression of microRNAs expression, like miR155. An important function is to allow GC B-cells to proliferate very rapidly in response to T-cell dependent antigens and tolerate the physiological DNA breaks required for immunglobulin class switch recombination and somatic hypermutation without inducing a p53/TP53-dependent apoptotic response. In follicular helper CD4(+) T-cells (T(FH) cells), promotes the expression of T(FH)-related genes but inhibits the differentiation of T(H)1, T(H)2 and T(H)17 cells. Also required for the establishment and maintenance of immunological memory for both T- and B-cells. Suppresses macrophage proliferation through competition with STAT5 for STAT-binding motifs binding on certain target genes, such as CCL2 and CCND2. In response to genotoxic stress, controls cell cycle arrest in GC B-cells in both p53/TP53-dependedent and -independent manners. Besides, also controls neurogenesis through the alteration of the composition of NOTCH-dependent transcriptional complexes at selective NOTCH targets, such as HES5, including the recruitment of the deacetylase SIRT1 and resulting in an epigenetic silencing leading to neuronal differentiation.
• Tissue Specificity: Expressed in germinal center T- and B-cells and in primary immature dendritic cells.
• KEGG Pathway:
  FoxO sig.ling pathway (hsa04068)
  Transcriptio.l misregulation in cancer (hsa05202)
  Chemical carcinogenesis - receptor activation (hsa05207)
• Reactome Pathway:
  TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain (R-HSA-6803205)
  FOXO-mediated transcription of cell death genes (R-HSA-9614657)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)

Molecular Interaction Atlas (MIA) of This DOT

35 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of B-cell lymphoma 6 protein (BCL6).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of B-cell lymphoma 6 protein (BCL6).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of B-cell lymphoma 6 protein (BCL6).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of B-cell lymphoma 6 protein (BCL6).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of B-cell lymphoma 6 protein (BCL6).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of B-cell lymphoma 6 protein (BCL6).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of B-cell lymphoma 6 protein (BCL6).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of B-cell lymphoma 6 protein (BCL6).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of B-cell lymphoma 6 protein (BCL6).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of B-cell lymphoma 6 protein (BCL6).	[10]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of B-cell lymphoma 6 protein (BCL6).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of B-cell lymphoma 6 protein (BCL6).	[9]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of B-cell lymphoma 6 protein (BCL6).	[12]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of B-cell lymphoma 6 protein (BCL6).	[13]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of B-cell lymphoma 6 protein (BCL6).	[14]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of B-cell lymphoma 6 protein (BCL6).	[15]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of B-cell lymphoma 6 protein (BCL6).	[8]
Lindane	DMB8CNL	Approved	Lindane increases the expression of B-cell lymphoma 6 protein (BCL6).	[8]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate increases the expression of B-cell lymphoma 6 protein (BCL6).	[16]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of B-cell lymphoma 6 protein (BCL6).	[17]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of B-cell lymphoma 6 protein (BCL6).	[18]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of B-cell lymphoma 6 protein (BCL6).	[19]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of B-cell lymphoma 6 protein (BCL6).	[20]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of B-cell lymphoma 6 protein (BCL6).	[21]
Sodium stibogluconate	DMH5MVE	Phase 2	Sodium stibogluconate decreases the expression of B-cell lymphoma 6 protein (BCL6).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of B-cell lymphoma 6 protein (BCL6).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of B-cell lymphoma 6 protein (BCL6).	[23]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of B-cell lymphoma 6 protein (BCL6).	[24]
PF-3758309	DM36PKZ	Phase 1	PF-3758309 increases the expression of B-cell lymphoma 6 protein (BCL6).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of B-cell lymphoma 6 protein (BCL6).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of B-cell lymphoma 6 protein (BCL6).	[29]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of B-cell lymphoma 6 protein (BCL6).	[30]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of B-cell lymphoma 6 protein (BCL6).	[31]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of B-cell lymphoma 6 protein (BCL6).	[32]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of B-cell lymphoma 6 protein (BCL6).	[33]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of B-cell lymphoma 6 protein (BCL6).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of B-cell lymphoma 6 protein (BCL6).	[28]

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