Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFT924M)

• DOT 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
• Related Disease:
  Ectodermal dysplasia and immunodeficiency 2
  Ectodermal dysplasia and immune deficiency
• UniProt ID: IKBA_HUMAN
• PDB ID: 1IKN; 1NFI; 6TTU; 6Y1J
• Pfam ID: PF12796 ; PF13857
• Sequence:
  MFQAAERPQEWAMEGPRDGLKKERLLDDRHDSGLDSMKDEEYEQMVKELQEIRLEPQEVP
  RGSEPWKQQLTEDGDSFLHLAIIHEEKALTMEVIRQVKGDLAFLNFQNNLQQTPLHLAVI
  TNQPEIAEALLGAGCDPELRDFRGNTPLHLACEQGCLASVGVLTQSCTTPHLHSILKATN
  YNGHTCLHLASIHGYLGIVELLVSLGADVNAQEPCNGRTALHLAVDLQNPDLVSLLLKCG
  ADVNRVTYQGYSPYQLTWGRPSTRIQQQLGQLTLENLQMLPESEDEESYDTESEFTEFTE
  DELPYDDCVFGGQRLTL
• Function: Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals. On cellular stimulation by immune and pro-inflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Chemokine sig.ling pathway (hsa04062)
  NF-kappa B sig.ling pathway (hsa04064)
  Apoptosis (hsa04210)
  Osteoclast differentiation (hsa04380)
  Toll-like receptor sig.ling pathway (hsa04620)
  NOD-like receptor sig.ling pathway (hsa04621)
  RIG-I-like receptor sig.ling pathway (hsa04622)
  Cytosolic D.-sensing pathway (hsa04623)
  C-type lectin receptor sig.ling pathway (hsa04625)
  IL-17 sig.ling pathway (hsa04657)
  Th1 and Th2 cell differentiation (hsa04658)
  Th17 cell differentiation (hsa04659)
  T cell receptor sig.ling pathway (hsa04660)
  B cell receptor sig.ling pathway (hsa04662)
  TNF sig.ling pathway (hsa04668)
  Neurotrophin sig.ling pathway (hsa04722)
  Adipocytokine sig.ling pathway (hsa04920)
  Relaxin sig.ling pathway (hsa04926)
  Insulin resistance (hsa04931)
  Alcoholic liver disease (hsa04936)
  Epithelial cell sig.ling 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)
  Coro.virus 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)
  SARS-CoV-1 activates/modulates innate immune responses (R-HSA-9692916)
  Activation of NF-kappaB in B cells (R-HSA-1169091)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ectodermal dysplasia and immunodeficiency 2	DISQW1LU	Strong	Autosomal dominant	[1]
Ectodermal dysplasia and immune deficiency	DISLMZXR	Supportive	Autosomal dominant	[2]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	NF-kappa-B inhibitor alpha (NFKBIA) increases the response to substance of Temozolomide.	[95]
Irinotecan	DMP6SC2	Approved	NF-kappa-B inhibitor alpha (NFKBIA) increases the response to substance of Irinotecan.	[96]
DTI-015	DMXZRW0	Approved	NF-kappa-B inhibitor alpha (NFKBIA) increases the response to substance of DTI-015.	[96]
Fructose	DM43AN2	Approved	NF-kappa-B inhibitor alpha (NFKBIA) increases the Metabolism and nutrition disorders ADR of Fructose.	[97]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[14]
Marinol	DM70IK5	Approved	Marinol decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[15]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[16]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[17]
Menadione	DMSJDTY	Approved	Menadione affects the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[18]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[9]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[20]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[22]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[24]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[25]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[26]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[29]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[33]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[40]
Sorafenib	DMS8IFC	Approved	Sorafenib increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[41]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[42]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[43]
Morphine	DMRMS0L	Approved	Morphine increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[47]
Romidepsin	DMT5GNL	Approved	Romidepsin increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[49]
Trovafloxacin	DM6AN32	Approved	Trovafloxacin increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[50]
Sulfasalazine	DMICA9H	Approved	Sulfasalazine decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[52]
Salbutamol	DMN9CWF	Approved	Salbutamol increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[54]
Ibrutinib	DMHZCPO	Approved	Ibrutinib decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[56]
Cilostazol	DMZMSCT	Approved	Cilostazol increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[57]
Methadone	DMTW6IU	Approved	Methadone increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[47]
Fentanyl	DM8WAHT	Approved	Fentanyl increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[47]
Rimexolone	DMTAREC	Approved	Rimexolone increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[60]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[61]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[62]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[63]
Resatorvid	DMFMWYC	Phase 3	Resatorvid decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[66]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[67]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[68]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[69]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[49]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[70]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[71]
Flavopiridol	DMKSUOI	Phase 2	Flavopiridol increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[73]
Pelitinib	DMIW453	Phase 2	Pelitinib increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[74]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[75]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[76]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[77]
GM6001	DM7V9CT	Discontinued in Phase 2	GM6001 increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[81]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[82]
Ciglitazone	DMAPO0T	Preclinical	Ciglitazone decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[84]
EMODIN	DMAEDQG	Terminated	EMODIN increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[86]
SB 203580	DMAET6F	Terminated	SB 203580 decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[87]
NS398	DMINUWH	Terminated	NS398 decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[84]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[89]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[90]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[91]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[92]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[93]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of NF-kappa-B inhibitor alpha (NFKBIA).	[94]

13 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the degradation of NF-kappa-B inhibitor alpha (NFKBIA).	[4]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the degradation of NF-kappa-B inhibitor alpha (NFKBIA).	[19]
Etoposide	DMNH3PG	Approved	Etoposide increases the degradation of NF-kappa-B inhibitor alpha (NFKBIA).	[30]
Capsaicin	DMGMF6V	Approved	Capsaicin decreases the degradation of NF-kappa-B inhibitor alpha (NFKBIA).	[36]
Methamphetamine	DMPM4SK	Approved	Methamphetamine increases the degradation of NF-kappa-B inhibitor alpha (NFKBIA).	[37]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the degradation of NF-kappa-B inhibitor alpha (NFKBIA).	[38]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the degradation of NF-kappa-B inhibitor alpha (NFKBIA).	[39]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus decreases the degradation of NF-kappa-B inhibitor alpha (NFKBIA).	[48]
Hydroxychloroquine	DMSIVND	Approved	Hydroxychloroquine increases the degradation of NF-kappa-B inhibitor alpha (NFKBIA).	[53]
Thiopental	DMGP8AX	Approved	Thiopental decreases the degradation of NF-kappa-B inhibitor alpha (NFKBIA).	[58]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the degradation of NF-kappa-B inhibitor alpha (NFKBIA).	[79]
Dioscin	DM5H2W9	Preclinical	Dioscin decreases the degradation of NF-kappa-B inhibitor alpha (NFKBIA).	[83]
Piperlongumine	DMIZCOE	Preclinical	Piperlongumine affects the localization of NF-kappa-B inhibitor alpha (NFKBIA).	[85]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[13]
Folic acid	DMEMBJC	Approved	Folic acid increases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[21]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[23]
Hydroquinone	DM6AVR4	Approved	Hydroquinone affects the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[27]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[28]
Nicotine	DMWX5CO	Approved	Nicotine increases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[31]
Simvastatin	DM30SGU	Approved	Simvastatin increases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[32]
Sulindac	DM2QHZU	Approved	Sulindac decreases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[34]
Vinblastine	DM5TVS3	Approved	Vinblastine increases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[35]
Colchicine	DM2POTE	Approved	Colchicine increases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[35]
Imatinib	DM7RJXL	Approved	Imatinib increases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[44]
Ritonavir	DMU764S	Approved	Ritonavir decreases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[45]
Deoxycholic acid	DM3GYAL	Approved	Deoxycholic acid increases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[46]
Ergotidine	DM78IME	Approved	Ergotidine increases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[51]
Digitoxin	DMWVIGP	Approved	Digitoxin decreases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[55]
Aprepitant	DM053KT	Approved	Aprepitant decreases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[59]
MLN4924	DMP36KD	Phase 3	MLN4924 increases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[64]
Peretinoin	DMESAZK	Phase 3	Peretinoin decreases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[65]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin decreases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[72]
NVP-AUY922	DMTYXQF	Phase 2	NVP-AUY922 affects the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[72]
VS-5584	DMMO3G5	Phase 1	VS-5584 decreases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[78]
TDZD-8	DMG6Q45	Patented	TDZD-8 increases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[80]
B-581	DM5EKPM	Terminated	B-581 decreases the phosphorylation of NF-kappa-B inhibitor alpha (NFKBIA).	[88]

References

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