Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU728KS)

• DOT Name: NF-kappa-B inhibitor zeta (NFKBIZ)
• Synonyms: I-kappa-B-zeta; IkB-zeta; IkappaBzeta; IL-1 inducible nuclear ankyrin-repeat protein; INAP; Molecule possessing ankyrin repeats induced by lipopolysaccharide; MAIL
• Gene Name: NFKBIZ
• Related Disease:
  Non-insulin dependent diabetes
  Psoriasis
  Atopic dermatitis
  Coronary atherosclerosis
  Coronary heart disease
  Crohn disease
  Pneumococcal infection
  Adult glioblastoma
  Glioblastoma multiforme
  Cutaneous melanoma
  Hereditary nonpolyposis colon cancer
  Lynch syndrome 1
  Lynch syndrome 2
  Mycosis fungoides
  Neoplasm
  Primary cutaneous T-cell lymphoma
• UniProt ID: IKBZ_HUMAN
• Pfam ID: PF12796
• Sequence:
  MIVDKLLDDSRGGEGLRDAAGGCGLMTSPLNLSYFYGASPPAAAPGACDASCSVLGPSAP
  GSPGSDSSDFSSASSVSSCGAVESRSRGGARAERQPVEPHMGVGRQQRGPFQGVRVKNSV
  KELLLHIRSHKQKASGQAVDDFKTQGVNIEQFRELKNTVSYSGKRKGPDSLSDGPACKRP
  ALLHSQFLTPPQTPTPGESMEDVHLNEPKQESSADLLQNIINIKNECSPVSLNTVQVSWL
  NPVVVPQSSPAEQCQDFHGGQVFSPPQKCQPFQVRGSQQMIDQASLYQYSPQNQHVEQQP
  HYTHKPTLEYSPFPIPPQSPAYEPNLFDGPESQFCPNQSLVSLLGDQRESENIANPMQTS
  SSVQQQNDAHLHSFSMMPSSACEAMVGHEMASDSSNTSLPFSNMGNPMNTTQLGKSLFQW
  QVEQEESKLANISQDQFLSKDADGDTFLHIAVAQGRRALSYVLARKMNALHMLDIKEHNG
  QSAFQVAVAANQHLIVQDLVNIGAQVNTTDCWGRTPLHVCAEKGHSQVLQAIQKGAVGSN
  QFVDLEATNYDGLTPLHCAVIAHNAVVHELQRNQQPHSPEVQELLLKNKSLVDTIKCLIQ
  MGAAVEAKDRKSGRTALHLAAEEANLELIRLFLELPSCLSFVNAKAYNGNTALHVAASLQ
  YRLTQLDAVRLLMRKGADPSTRNLENEQPVHLVPDGPVGEQIRRILKGKSIQQRAPPY
• Function: Involved in regulation of NF-kappa-B transcription factor complexes. Inhibits NF-kappa-B activity without affecting its nuclear translocation upon stimulation. Inhibits DNA-binding of RELA and NFKB1/p50, and of the NF-kappa-B p65-p50 heterodimer and the NF-kappa-B p50-p50 homodimer. Seems also to activate NF-kappa-B-mediated transcription. In vitro, upon association with NFKB1/p50 has transcriptional activation activity and, together with NFKB1/p50 and RELA, is recruited to LCN2 promoters. Promotes transcription of LCN2 and DEFB4. Is recruited to IL-6 promoters and activates IL-6 but decreases TNF-alpha production in response to LPS. Seems to be involved in the induction of inflammatory genes activated through TLR/IL-1 receptor signaling. Involved in the induction of T helper 17 cells (Th17) differentiation upon recognition of antigen by T cell antigen receptor (TCR).
• Tissue Specificity: Expressed at high levels in peripheral blood leukocytes and lung, at moderate levels in liver, placenta, and at low levels in spleen, kidney, skeletal muscle and heart.
• KEGG Pathway: Transcriptio.l misregulation in cancer (hsa05202)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[1]
Psoriasis	DIS59VMN	Definitive	Altered Expression	[2]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[3]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[4]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[4]
Crohn disease	DIS2C5Q8	Strong	Altered Expression	[5]
Pneumococcal infection	DIS6SXQD	Strong	Genetic Variation	[6]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[7]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[7]
Cutaneous melanoma	DIS3MMH9	Limited	Biomarker	[8]
Hereditary nonpolyposis colon cancer	DISPA49R	Limited	Autosomal dominant	[9]
Lynch syndrome 1	DISSABLZ	Limited	Biomarker	[10]
Lynch syndrome 2	DISRLYU1	Limited	Biomarker	[10]
Mycosis fungoides	DIS62RB8	Limited	Altered Expression	[11]
Neoplasm	DISZKGEW	Limited	Biomarker	[8]
Primary cutaneous T-cell lymphoma	DIS35WVW	Limited	Altered Expression	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of NF-kappa-B inhibitor zeta (NFKBIZ).	[12]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of NF-kappa-B inhibitor zeta (NFKBIZ).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of NF-kappa-B inhibitor zeta (NFKBIZ).	[33]

24 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 NF-kappa-B inhibitor zeta (NFKBIZ).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[17]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[18]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[20]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[17]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[21]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[22]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[23]
Aspirin	DM672AH	Approved	Aspirin increases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[24]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[25]
Sanguinarine	DMDINFS	Approved	Sanguinarine increases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[26]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[27]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[28]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[29]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[30]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[31]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[32]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[34]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[35]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[36]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of NF-kappa-B inhibitor zeta (NFKBIZ).	[37]

References

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