Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT16N9ZO)

• DOT Name: Cytochrome b-245 light chain (CYBA)
• Synonyms: Cytochrome b(558) alpha chain; Cytochrome b558 subunit alpha; Neutrophil cytochrome b 22 kDa polypeptide; Superoxide-generating NADPH oxidase light chain subunit; p22 phagocyte B-cytochrome; p22-phox; p22phox
• Gene Name: CYBA
• Related Disease:
  Chronic kidney disease
  Rheumatoid arthritis
  Tuberculosis
  Acute myocardial infarction
  Arteriosclerosis
  Asthma
  B-cell lymphoma
  B-cell neoplasm
  Cardiac disease
  Cardiovascular disease
  Cerebrovascular disease
  Cervical cancer
  Cervical carcinoma
  Chronic renal failure
  Diabetic retinopathy
  Essential hypertension
  Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative
  Hepatitis C virus infection
  Leukemia
  Liver cirrhosis
  Myelodysplastic syndrome
  Neoplasm
  Nephropathy
  Non-alcoholic fatty liver disease
  Osteoarthritis
  Pulmonary hypertension
  Squamous cell carcinoma
  Systemic lupus erythematosus
  Systemic sclerosis
  Type-1 diabetes
  Type-1/2 diabetes
  Vascular disease
  End-stage renal disease
  Granulomatous disease, chronic, X-linked
  Hepatocellular carcinoma
  Pulmonary disease
  Chronic granulomatous disease
  Atherosclerosis
  Breast cancer
  Breast carcinoma
  Chronic obstructive pulmonary disease
  Glaucoma/ocular hypertension
  Hyperglycemia
  Kidney failure
  Nervous system inflammation
  Non-hodgkin lymphoma
  Obesity
  Stroke
• UniProt ID: CY24A_HUMAN
• PDB ID: 1WLP; 7U8G; 7YXW; 8GZ3
• Pfam ID: PF05038
• Sequence:
  MGQIEWAMWANEQALASGLILITGGIVATAGRFTQWYFGAYSIVAGVFVCLLEYPRGKRK
  KGSTMERWGQKYMTAVVKLFGPFTRNYYVRAVLHLLLSVPAGFLLATILGTACLAIASGI
  YLLAAVRGEQWTPIEPKPRERPQIGGTIKQPPSNPPPRPPAEARKKPSEEEAAVAAGGPP
  GGPQVNPIPVTDEVV
• Function: Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. Associates with NOX3 to form a functional NADPH oxidase constitutively generating superoxide.
• KEGG Pathway:
  Phagosome (hsa04145)
  Osteoclast differentiation (hsa04380)
  Neutrophil extracellular trap formation (hsa04613)
  NOD-like receptor sig.ling pathway (hsa04621)
  Leukocyte transendothelial migration (hsa04670)
  Prion disease (hsa05020)
  Leishmaniasis (hsa05140)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Diabetic cardiomyopathy (hsa05415)
  Lipid and atherosclerosis (hsa05417)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Cross-presentation of particulate exogenous antigens (phagosomes) (R-HSA-1236973)
  Detoxification of Reactive Oxygen Species (R-HSA-3299685)
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  RHO GTPases Activate NADPH Oxidases (R-HSA-5668599)
  Neutrophil degranulation (R-HSA-6798695)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RAC3 GTPase cycle (R-HSA-9013423)
  WNT5 (R-HSA-9673324)
  ROS and RNS production in phagocytes (R-HSA-1222556)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic kidney disease	DISW82R7	Definitive	Genetic Variation	[1]
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[2]
Tuberculosis	DIS2YIMD	Definitive	Genetic Variation	[3]
Acute myocardial infarction	DISE3HTG	Strong	Genetic Variation	[4]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[5]
Asthma	DISW9QNS	Strong	Biomarker	[6]
B-cell lymphoma	DISIH1YQ	Strong	Genetic Variation	[7]
B-cell neoplasm	DISVY326	Strong	Biomarker	[8]
Cardiac disease	DISVO1I5	Strong	Genetic Variation	[9]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[10]
Cerebrovascular disease	DISAB237	Strong	Genetic Variation	[11]
Cervical cancer	DISFSHPF	Strong	Biomarker	[12]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[12]
Chronic renal failure	DISGG7K6	Strong	Genetic Variation	[13]
Diabetic retinopathy	DISHGUJM	Strong	Biomarker	[14]
Essential hypertension	DIS7WI98	Strong	Biomarker	[15]
Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	DIS3QSS3	Strong	Autosomal recessive	[16]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[17]
Leukemia	DISNAKFL	Strong	Altered Expression	[18]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[19]
Myelodysplastic syndrome	DISYHNUI	Strong	Posttranslational Modification	[20]
Neoplasm	DISZKGEW	Strong	Biomarker	[21]
Nephropathy	DISXWP4P	Strong	Genetic Variation	[22]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[23]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[24]
Pulmonary hypertension	DIS1RSP5	Strong	Biomarker	[25]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[21]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[26]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[27]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[28]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[13]
Vascular disease	DISVS67S	Strong	Altered Expression	[26]
End-stage renal disease	DISXA7GG	moderate	Genetic Variation	[13]
Granulomatous disease, chronic, X-linked	DISNTTS3	moderate	Genetic Variation	[29]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[30]
Pulmonary disease	DIS6060I	moderate	Genetic Variation	[31]
Chronic granulomatous disease	DIS9ZR24	Supportive	Autosomal recessive	[32]
Atherosclerosis	DISMN9J3	Limited	Genetic Variation	[5]
Breast cancer	DIS7DPX1	Limited	Genetic Variation	[33]
Breast carcinoma	DIS2UE88	Limited	Genetic Variation	[33]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Biomarker	[34]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Genetic Variation	[35]
Hyperglycemia	DIS0BZB5	Limited	Altered Expression	[36]
Kidney failure	DISOVQ9P	Limited	Genetic Variation	[37]
Nervous system inflammation	DISB3X5A	Limited	Altered Expression	[38]
Non-hodgkin lymphoma	DISS2Y8A	Limited	Genetic Variation	[39]
Obesity	DIS47Y1K	Limited	Altered Expression	[40]
Stroke	DISX6UHX	Limited	Biomarker	[41]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Cytochrome b-245 light chain (CYBA) affects the response to substance of Arsenic.	[73]
Simvastatin	DM30SGU	Approved	Cytochrome b-245 light chain (CYBA) affects the response to substance of Simvastatin.	[74]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Cytochrome b-245 light chain (CYBA).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cytochrome b-245 light chain (CYBA).	[62]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Cytochrome b-245 light chain (CYBA).	[64]

33 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 Cytochrome b-245 light chain (CYBA).	[43]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cytochrome b-245 light chain (CYBA).	[44]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cytochrome b-245 light chain (CYBA).	[45]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cytochrome b-245 light chain (CYBA).	[46]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cytochrome b-245 light chain (CYBA).	[47]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Cytochrome b-245 light chain (CYBA).	[48]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Cytochrome b-245 light chain (CYBA).	[49]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Cytochrome b-245 light chain (CYBA).	[50]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cytochrome b-245 light chain (CYBA).	[51]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Cytochrome b-245 light chain (CYBA).	[52]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Cytochrome b-245 light chain (CYBA).	[53]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Cytochrome b-245 light chain (CYBA).	[54]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Cytochrome b-245 light chain (CYBA).	[55]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Cytochrome b-245 light chain (CYBA).	[53]
Bezafibrate	DMZDCS0	Approved	Bezafibrate decreases the expression of Cytochrome b-245 light chain (CYBA).	[53]
Glucosamine	DM4ZLFD	Approved	Glucosamine decreases the expression of Cytochrome b-245 light chain (CYBA).	[56]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus increases the expression of Cytochrome b-245 light chain (CYBA).	[57]
Candesartan	DMRK8OT	Approved	Candesartan decreases the expression of Cytochrome b-245 light chain (CYBA).	[58]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Cytochrome b-245 light chain (CYBA).	[44]
Manidipine	DMJPGUA	Phase 3	Manidipine decreases the expression of Cytochrome b-245 light chain (CYBA).	[59]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Cytochrome b-245 light chain (CYBA).	[60]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Cytochrome b-245 light chain (CYBA).	[61]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Cytochrome b-245 light chain (CYBA).	[53]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cytochrome b-245 light chain (CYBA).	[63]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Cytochrome b-245 light chain (CYBA).	[65]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cytochrome b-245 light chain (CYBA).	[66]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Cytochrome b-245 light chain (CYBA).	[67]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Cytochrome b-245 light chain (CYBA).	[68]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Cytochrome b-245 light chain (CYBA).	[69]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Cytochrome b-245 light chain (CYBA).	[70]
methylglyoxal	DMRC3OZ	Investigative	methylglyoxal increases the expression of Cytochrome b-245 light chain (CYBA).	[71]
Icosapentum	DMF1CM7	Investigative	Icosapentum decreases the expression of Cytochrome b-245 light chain (CYBA).	[53]
Oxalic Acid	DMLN2GQ	Investigative	Oxalic Acid increases the expression of Cytochrome b-245 light chain (CYBA).	[72]

References

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