Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC1W6UX)

• DOT Name: Heme oxygenase 1 (HMOX1)
• Synonyms: HO-1; EC 1.14.14.18
• Gene Name: HMOX1
• Related Disease:
  Heme oxygenase 1 deficiency
  Chronic obstructive pulmonary disease
• UniProt ID: HMOX1_HUMAN
• PDB ID: 1N3U; 1N45; 1NI6; 1OYK; 1OYL; 1OZE; 1OZL; 1OZR; 1OZW; 1S13; 1S8C; 1T5P; 1TWN; 1TWR; 1XJZ; 1XK0; 1XK1; 1XK2; 1XK3; 3CZY; 3HOK; 3K4F; 3TGM; 4WD4; 5BTQ; 6EHA
• EC Number: 1.14.14.18
• Pfam ID: PF01126
• Sequence:
  MERPQPDSMPQDLSEALKEATKEVHTQAENAEFMRNFQKGQVTRDGFKLVMASLYHIYVA
  LEEEIERNKESPVFAPVYFPEELHRKAALEQDLAFWYGPRWQEVIPYTPAMQRYVKRLHE
  VGRTEPELLVAHAYTRYLGDLSGGQVLKKIAQKALDLPSSGEGLAFFTFPNIASATKFKQ
  LYRSRMNSLEMTPAVRQRVIEEAKTAFLLNIQLFEELQELLTHDTKDQSPSRAPGLRQRA
  SNKVQDSAPVETPRGKPPLNTRSQAPLLRWVLTLSFLVATVAVGLYAM
• Function: [Heme oxygenase 1]: Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron. Affords protection against programmed cell death and this cytoprotective effect relies on its ability to catabolize free heme and prevent it from sensitizing cells to undergo apoptosis ; [Heme oxygenase 1]: (Microbial infection) During SARS-COV-2 infection, promotes SARS-CoV-2 ORF3A-mediated autophagy but is unlikely to be required for ORF3A-mediated induction of reticulophagy; [Heme oxygenase 1 soluble form]: Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron.
• Tissue Specificity: Expressed at higher levels in renal cancer tissue than in normal tissue (at protein level).
• KEGG Pathway:
  Porphyrin metabolism (hsa00860)
  Metabolic pathways (hsa01100)
  HIF-1 sig.ling pathway (hsa04066)
  Ferroptosis (hsa04216)
  Mineral absorption (hsa04978)
  Pathways in cancer (hsa05200)
  MicroR.s in cancer (hsa05206)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Hepatocellular carcinoma (hsa05225)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  The NLRP3 inflammasome (R-HSA-844456)
  Iron uptake and transport (R-HSA-917937)
  Insertion of tail-anchored proteins into the endoplasmic reticulum membrane (R-HSA-9609523)
  Purinergic signaling in leishmaniasis infection (R-HSA-9660826)
  Cytoprotection by HMOX1 (R-HSA-9707564)
  Regulation of HMOX1 expression and activity (R-HSA-9707587)
  Heme signaling (R-HSA-9707616)
  NFE2L2 regulating anti-oxidant/detoxification enzymes (R-HSA-9818027)
  Heme degradation (R-HSA-189483)
• BioCyc Pathway: MetaCyc:HS02027-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Heme oxygenase 1 deficiency	DISAP2FR	Strong	Autosomal recessive	[1]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Unknown	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Nitric Oxide	DM1RBYG	Approved	Heme oxygenase 1 (HMOX1) decreases the response to substance of Nitric Oxide.	[85]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Heme oxygenase 1 (HMOX1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Heme oxygenase 1 (HMOX1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Heme oxygenase 1 (HMOX1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Heme oxygenase 1 (HMOX1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Heme oxygenase 1 (HMOX1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Heme oxygenase 1 (HMOX1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Heme oxygenase 1 (HMOX1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Heme oxygenase 1 (HMOX1).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Heme oxygenase 1 (HMOX1).	[11]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Heme oxygenase 1 (HMOX1).	[12]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Heme oxygenase 1 (HMOX1).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Heme oxygenase 1 (HMOX1).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Heme oxygenase 1 (HMOX1).	[15]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Heme oxygenase 1 (HMOX1).	[16]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Heme oxygenase 1 (HMOX1).	[17]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Heme oxygenase 1 (HMOX1).	[17]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Heme oxygenase 1 (HMOX1).	[18]
Carbamazepine	DMZOLBI	Approved	Carbamazepine increases the expression of Heme oxygenase 1 (HMOX1).	[19]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Heme oxygenase 1 (HMOX1).	[20]
Marinol	DM70IK5	Approved	Marinol increases the expression of Heme oxygenase 1 (HMOX1).	[21]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Heme oxygenase 1 (HMOX1).	[22]
Selenium	DM25CGV	Approved	Selenium increases the expression of Heme oxygenase 1 (HMOX1).	[23]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Heme oxygenase 1 (HMOX1).	[24]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Heme oxygenase 1 (HMOX1).	[25]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Heme oxygenase 1 (HMOX1).	[26]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Heme oxygenase 1 (HMOX1).	[27]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Heme oxygenase 1 (HMOX1).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Heme oxygenase 1 (HMOX1).	[28]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Heme oxygenase 1 (HMOX1).	[21]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Heme oxygenase 1 (HMOX1).	[29]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Heme oxygenase 1 (HMOX1).	[30]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Heme oxygenase 1 (HMOX1).	[31]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Heme oxygenase 1 (HMOX1).	[32]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Heme oxygenase 1 (HMOX1).	[33]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Heme oxygenase 1 (HMOX1).	[34]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Heme oxygenase 1 (HMOX1).	[35]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of Heme oxygenase 1 (HMOX1).	[36]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Heme oxygenase 1 (HMOX1).	[37]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Heme oxygenase 1 (HMOX1).	[36]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Heme oxygenase 1 (HMOX1).	[38]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Heme oxygenase 1 (HMOX1).	[39]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Heme oxygenase 1 (HMOX1).	[40]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Heme oxygenase 1 (HMOX1).	[41]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Heme oxygenase 1 (HMOX1).	[42]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Heme oxygenase 1 (HMOX1).	[40]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Heme oxygenase 1 (HMOX1).	[43]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Heme oxygenase 1 (HMOX1).	[44]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Heme oxygenase 1 (HMOX1).	[40]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of Heme oxygenase 1 (HMOX1).	[45]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Heme oxygenase 1 (HMOX1).	[46]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Heme oxygenase 1 (HMOX1).	[47]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Heme oxygenase 1 (HMOX1).	[47]
Vitamin C	DMXJ7O8	Approved	Vitamin C increases the expression of Heme oxygenase 1 (HMOX1).	[48]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil decreases the expression of Heme oxygenase 1 (HMOX1).	[40]
Ritonavir	DMU764S	Approved	Ritonavir increases the expression of Heme oxygenase 1 (HMOX1).	[49]
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin increases the expression of Heme oxygenase 1 (HMOX1).	[50]
Dactinomycin	DM2YGNW	Approved	Dactinomycin decreases the expression of Heme oxygenase 1 (HMOX1).	[51]
Ampicillin	DMHWE7P	Approved	Ampicillin increases the expression of Heme oxygenase 1 (HMOX1).	[19]
Bosentan	DMIOGBU	Approved	Bosentan increases the expression of Heme oxygenase 1 (HMOX1).	[52]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the expression of Heme oxygenase 1 (HMOX1).	[53]
Lovastatin	DM9OZWQ	Approved	Lovastatin increases the expression of Heme oxygenase 1 (HMOX1).	[41]
Deoxycholic acid	DM3GYAL	Approved	Deoxycholic acid increases the expression of Heme oxygenase 1 (HMOX1).	[54]
Glucosamine	DM4ZLFD	Approved	Glucosamine increases the expression of Heme oxygenase 1 (HMOX1).	[55]
Gentamicin	DMKINJO	Approved	Gentamicin increases the expression of Heme oxygenase 1 (HMOX1).	[56]
Glutathione	DMAHMT9	Approved	Glutathione affects the expression of Heme oxygenase 1 (HMOX1).	[57]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Approved	Eicosapentaenoic acid/docosa-hexaenoic acid increases the expression of Heme oxygenase 1 (HMOX1).	[58]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus increases the expression of Heme oxygenase 1 (HMOX1).	[56]
Dihydroxyacetone	DMM1LG2	Approved	Dihydroxyacetone increases the expression of Heme oxygenase 1 (HMOX1).	[59]
Atazanavir	DMSYRBX	Approved	Atazanavir increases the expression of Heme oxygenase 1 (HMOX1).	[60]
Penicillamine	DM40EF6	Approved	Penicillamine increases the expression of Heme oxygenase 1 (HMOX1).	[61]
Omeprazole	DM471KJ	Approved	Omeprazole increases the expression of Heme oxygenase 1 (HMOX1).	[62]
Hesperetin	DMKER83	Approved	Hesperetin increases the expression of Heme oxygenase 1 (HMOX1).	[63]
Fructose	DM43AN2	Approved	Fructose increases the expression of Heme oxygenase 1 (HMOX1).	[64]
Nifedipine	DMSVOZT	Approved	Nifedipine increases the expression of Heme oxygenase 1 (HMOX1).	[65]
Lapatinib	DM3BH1Y	Approved	Lapatinib increases the expression of Heme oxygenase 1 (HMOX1).	[66]
Benzoic acid	DMKB9FI	Approved	Benzoic acid increases the expression of Heme oxygenase 1 (HMOX1).	[37]
Gamolenic acid	DMQN30Z	Approved	Gamolenic acid increases the expression of Heme oxygenase 1 (HMOX1).	[67]
Carvedilol	DMHTEAO	Approved	Carvedilol increases the expression of Heme oxygenase 1 (HMOX1).	[68]
Allopurinol	DMLPAOB	Approved	Allopurinol increases the expression of Heme oxygenase 1 (HMOX1).	[19]
Norepinephrine	DMOUC09	Approved	Norepinephrine increases the expression of Heme oxygenase 1 (HMOX1).	[53]
Ethacrynic acid	DM60QMR	Approved	Ethacrynic acid increases the expression of Heme oxygenase 1 (HMOX1).	[69]
Gallium nitrate	DMF9O6B	Approved	Gallium nitrate increases the expression of Heme oxygenase 1 (HMOX1).	[70]
Ropivacaine	DMSPJG2	Approved	Ropivacaine increases the expression of Heme oxygenase 1 (HMOX1).	[71]
Lansoprazole	DMXYLQ3	Approved	Lansoprazole increases the expression of Heme oxygenase 1 (HMOX1).	[62]
Pantothenic acid	DM091H2	Approved	Pantothenic acid increases the expression of Heme oxygenase 1 (HMOX1).	[72]
Cilostazol	DMZMSCT	Approved	Cilostazol increases the expression of Heme oxygenase 1 (HMOX1).	[73]
Furazolidone	DM3P6V7	Approved	Furazolidone increases the expression of Heme oxygenase 1 (HMOX1).	[74]
Lopinavir	DMITQS0	Approved	Lopinavir increases the expression of Heme oxygenase 1 (HMOX1).	[60]
Roflumilast	DMPGHY8	Approved	Roflumilast increases the expression of Heme oxygenase 1 (HMOX1).	[75]
Bromocriptine	DMVE3TK	Approved	Bromocriptine increases the expression of Heme oxygenase 1 (HMOX1).	[76]
Ammonia	DMOEVK6	Approved	Ammonia increases the expression of Heme oxygenase 1 (HMOX1).	[77]
Urea	DMUK75B	Approved	Urea increases the expression of Heme oxygenase 1 (HMOX1).	[78]
Tecfidera	DM2OVDT	Approved	Tecfidera increases the expression of Heme oxygenase 1 (HMOX1).	[79]
Idarubicin	DMM0XGL	Approved	Idarubicin increases the expression of Heme oxygenase 1 (HMOX1).	[56]
Tobramycin	DMUI0CH	Approved	Tobramycin increases the expression of Heme oxygenase 1 (HMOX1).	[56]
Duloxetine	DM9BI7M	Approved	Duloxetine increases the expression of Heme oxygenase 1 (HMOX1).	[80]
Pentaerythritol tetranitrate	DMZ9MO5	Approved	Pentaerythritol tetranitrate increases the expression of Heme oxygenase 1 (HMOX1).	[82]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Heme oxygenase 1 (HMOX1).	[83]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of Heme oxygenase 1 (HMOX1).	[84]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclopirox	DMN5T2A	Approved	Ciclopirox decreases the degradation of Heme oxygenase 1 (HMOX1).	[81]

References

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