Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7T0TA4)

• DOT Name: Pro-adrenomedullin (ADM)
• Gene Name: ADM
• UniProt ID: ADML_HUMAN
• PDB ID: 2FLY; 2L7S; 4RWF; 5V6Y; 6UUN; 6UUS; 6V2E; 7VV0
• Pfam ID: PF00214
• Sequence:
  MKLVSVALMYLGSLAFLGADTARLDVASEFRKKWNKWALSRGKRELRMSSSYPTGLADVK
  AGPAQTLIRPQDMKGASRSPEDSSPDAARIRVKRYRQSMNNFQGLRSFGCRFGTCTVQKL
  AHQIYQFTDKDKDNVAPRSKISPQGYGRRRRRSLPEAGPGRTLVSSKPQAHGAPAPPSGS
  APHFL
• Function: AM and PAMP are potent hypotensive and vasodilatator agents. Numerous actions have been reported most related to the physiologic control of fluid and electrolyte homeostasis. In the kidney, am is diuretic and natriuretic, and both am and pamp inhibit aldosterone secretion by direct adrenal actions. In pituitary gland, both peptides at physiologically relevant doses inhibit basal ACTH secretion. Both peptides appear to act in brain and pituitary gland to facilitate the loss of plasma volume, actions which complement their hypotensive effects in blood vessels.
• Tissue Specificity: Highest levels found in pheochromocytoma and adrenal medulla. Also found in lung, ventricle and kidney tissues.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Vascular smooth muscle contraction (hsa04270)
• Reactome Pathway:
  Calcitonin-like ligand receptors (R-HSA-419812)
  G alpha (s) signalling events (R-HSA-418555)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Pro-adrenomedullin (ADM) affects the response to substance of Fluorouracil.	[44]
Cyclophosphamide	DM4O2Z7	Approved	Pro-adrenomedullin (ADM) affects the response to substance of Cyclophosphamide.	[44]
Phenylephrine	DMZHUO5	Approved	Pro-adrenomedullin (ADM) decreases the response to substance of Phenylephrine.	[45]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Nitrate	DMVFB93	Investigative	Pro-adrenomedullin (ADM) affects the abundance of Nitrate.	[45]

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 Pro-adrenomedullin (ADM).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Pro-adrenomedullin (ADM).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Pro-adrenomedullin (ADM).	[29]

42 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 Pro-adrenomedullin (ADM).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Pro-adrenomedullin (ADM).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Pro-adrenomedullin (ADM).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Pro-adrenomedullin (ADM).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Pro-adrenomedullin (ADM).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Pro-adrenomedullin (ADM).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Pro-adrenomedullin (ADM).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Pro-adrenomedullin (ADM).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Pro-adrenomedullin (ADM).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Pro-adrenomedullin (ADM).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Pro-adrenomedullin (ADM).	[13]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Pro-adrenomedullin (ADM).	[14]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Pro-adrenomedullin (ADM).	[15]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Pro-adrenomedullin (ADM).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Pro-adrenomedullin (ADM).	[17]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Pro-adrenomedullin (ADM).	[18]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Pro-adrenomedullin (ADM).	[19]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Pro-adrenomedullin (ADM).	[20]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Pro-adrenomedullin (ADM).	[11]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Pro-adrenomedullin (ADM).	[21]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Pro-adrenomedullin (ADM).	[22]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Pro-adrenomedullin (ADM).	[23]
Dinoprostone	DMTYOPD	Approved	Dinoprostone decreases the expression of Pro-adrenomedullin (ADM).	[24]
Vandetanib	DMRICNP	Approved	Vandetanib increases the expression of Pro-adrenomedullin (ADM).	[25]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Pro-adrenomedullin (ADM).	[26]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Pro-adrenomedullin (ADM).	[28]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Pro-adrenomedullin (ADM).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Pro-adrenomedullin (ADM).	[31]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Pro-adrenomedullin (ADM).	[32]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Pro-adrenomedullin (ADM).	[33]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Pro-adrenomedullin (ADM).	[34]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Pro-adrenomedullin (ADM).	[35]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Pro-adrenomedullin (ADM).	[36]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Pro-adrenomedullin (ADM).	[37]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Pro-adrenomedullin (ADM).	[38]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Pro-adrenomedullin (ADM).	[39]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Pro-adrenomedullin (ADM).	[40]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Pro-adrenomedullin (ADM).	[10]
Manganese	DMKT129	Investigative	Manganese increases the expression of Pro-adrenomedullin (ADM).	[41]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Pro-adrenomedullin (ADM).	[42]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide increases the expression of Pro-adrenomedullin (ADM).	[43]
Staurosporine	DM0E9BR	Investigative	Staurosporine decreases the expression of Pro-adrenomedullin (ADM).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the secretion of Pro-adrenomedullin (ADM).	[27]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the secretion of Pro-adrenomedullin (ADM).	[27]

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