Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: NF-kappa-B inhibitor alpha (NFKBIA)
• Synonyms: I-kappa-B-alpha; IkB-alpha; IkappaBalpha; Major histocompatibility complex enhancer-binding protein MAD3
• Gene Name: NFKBIA
• DTT Type: Clinical trial target; [1]
• UniProt ID: IKBA_HUMAN
• TTD ID: T51672
• Sequence:
  MFQAAERPQEWAMEGPRDGLKKERLLDDRHDSGLDSMKDEEYEQMVKELQEIRLEPQEVP
  RGSEPWKQQLTEDGDSFLHLAIIHEEKALTMEVIRQVKGDLAFLNFQNNLQQTPLHLAVI
  TNQPEIAEALLGAGCDPELRDFRGNTPLHLACEQGCLASVGVLTQSCTTPHLHSILKATN
  YNGHTCLHLASIHGYLGIVELLVSLGADVNAQEPCNGRTALHLAVDLQNPDLVSLLLKCG
  ADVNRVTYQGYSPYQLTWGRPSTRIQQQLGQLTLENLQMLPESEDEESYDTESEFTEFTE
  DELPYDDCVFGGQRLTL
• Function: Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL dimers in the cytoplasm through masking of their nuclear localization signals. On cellular stimulation by immune and proinflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription.
• KEGG Pathway:
  cAMP signaling pathway (hsa04024)
  Chemokine signaling pathway (hsa04062)
  NF-kappa B signaling pathway (hsa04064)
  Apoptosis (hsa04210)
  Osteoclast differentiation (hsa04380)
  Toll-like receptor signaling pathway (hsa04620)
  NOD-like receptor signaling pathway (hsa04621)
  RIG-I-like receptor signaling pathway (hsa04622)
  Cytosolic DNA-sensing pathway (hsa04623)
  C-type lectin receptor signaling pathway (hsa04625)
  IL-17 signaling pathway (hsa04657)
  Th1 and Th2 cell differentiation (hsa04658)
  Th17 cell differentiation (hsa04659)
  T cell receptor signaling pathway (hsa04660)
  B cell receptor signaling pathway (hsa04662)
  TNF signaling pathway (hsa04668)
  Neurotrophin signaling pathway (hsa04722)
  Adipocytokine signaling pathway (hsa04920)
  Relaxin signaling pathway (hsa04926)
  Insulin resistance (hsa04931)
  Alcoholic liver disease (hsa04936)
  Epithelial cell signaling in Helicobacter pylori infection (hsa05120)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
  Legionellosis (hsa05134)
  Yersinia infection (hsa05135)
  Leishmaniasis (hsa05140)
  Chagas disease (hsa05142)
  Toxoplasmosis (hsa05145)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Human cytomegalovirus infection (hsa05163)
  Influenza A (hsa05164)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
  Coronavirus disease - COVID-19 (hsa05171)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Prostate cancer (hsa05215)
  Chronic myeloid leukemia (hsa05220)
  Small cell lung cancer (hsa05222)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  RIP-mediated NFkB activation via ZBP1 (R-HSA-1810476)
  Downstream TCR signaling (R-HSA-202424)
  NF-kB is activated and signals survival (R-HSA-209560)
  FCERI mediated NF-kB activation (R-HSA-2871837)
  TAK1-dependent IKK and NF-kappa-B activation (R-HSA-445989)
  SUMOylation of immune response proteins (R-HSA-4755510)
  IkBA variant leads to EDA-ID (R-HSA-5603029)
  CLEC7A (Dectin-1) signaling (R-HSA-5607764)
  Ub-specific processing proteases (R-HSA-5689880)
  Interleukin-1 signaling (R-HSA-9020702)
  TRAF6 mediated NF-kB activation (R-HSA-933542)
  Activation of NF-kappaB in B cells (R-HSA-1169091)

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
I3C	DMIGFOR	Breast cancer	2C60-2C65	Phase 3	[1]
Fucoxanthin	DMPQFTA	Metabolic syndrome x	5C50-5D2Z	Phase 2	[2]

References

• [1] Protective effect of Indole-3-carbinol, an NF-B inhibitor in experimental paradigm of Parkinson's disease: In silico and in vivo studies. Brain Behav Immun. 2020 Nov;90:108-137.
• [2] Fucoxanthin inhibits the inflammatory response by suppressing the activation of NF-B and MAPKs in lipopolysaccharide-induced RAW 264.7 macrophages. Eur J Pharmacol. 2010 Dec 15;649(1-3):369-75.