Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRA8ZVE)

• DOT Name: Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF)
• Synonyms: PPIase F; EC 5.2.1.8; Cyclophilin D; CyP-D; CypD; Cyclophilin F; Mitochondrial cyclophilin; CyP-M; Rotamase F
• Gene Name: PPIF
• UniProt ID: PPIF_HUMAN
• PDB ID: 2BIT ; 2BIU ; 2Z6W ; 3QYU ; 3R49 ; 3R4G ; 3R54 ; 3R56 ; 3R57 ; 3R59 ; 3RCF ; 3RCG ; 3RCI ; 3RCK ; 3RCL ; 3RD9 ; 3RDA ; 3RDB ; 3RDC ; 4J58 ; 4J59 ; 4J5A ; 4J5B ; 4J5C ; 4J5D ; 4J5E ; 4O8H ; 4O8I ; 4XNC ; 4ZSC ; 4ZSD ; 5A0E ; 5CBT ; 5CBU ; 5CBV ; 5CBW ; 5CCN ; 5CCQ ; 5CCR ; 5CCS ; 6R8L ; 6R8O ; 6R8W ; 6R9S ; 6R9U ; 6R9X ; 6RA1 ; 6Y3E ; 6YBM ; 7OGI ; 7PMT ; 7R2H ; 7R2I ; 7R2J ; 7R2L ; 7TGS ; 7TGT ; 7TGU ; 7TGV ; 7TH1 ; 7TH6 ; 7TH7 ; 7THC ; 7THD ; 7THF ; 7ZDN ; 8EJX
• EC Number: 5.2.1.8
• Pfam ID: PF00160
• Sequence:
  MLALRCGSRWLGLLSVPRSVPLRLPAARACSKGSGDPSSSSSSGNPLVYLDVDANGKPLG
  RVVLELKADVVPKTAENFRALCTGEKGFGYKGSTFHRVIPSFMCQAGDFTNHNGTGGKSI
  YGSRFPDENFTLKHVGPGVLSMANAGPNTNGSQFFICTIKTDWLDGKHVVFGHVKEGMDV
  VKKIESFGSKSGRTSKKIVITDCGQLS
• Function: PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding. Involved in regulation of the mitochondrial permeability transition pore (mPTP). It is proposed that its association with the mPTP is masking a binding site for inhibiting inorganic phosphate (Pi) and promotes the open probability of the mPTP leading to apoptosis or necrosis; the requirement of the PPIase activity for this function is debated. In cooperation with mitochondrial p53/TP53 is involved in activating oxidative stress-induced necrosis. Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels. Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  cGMP-PKG sig.ling pathway (hsa04022)
  Neutrophil extracellular trap formation (hsa04613)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Huntington disease (hsa05016)
  Spinocerebellar ataxia (hsa05017)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Toxoplasmosis (hsa05145)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Diabetic cardiomyopathy (hsa05415)

Molecular Interaction Atlas (MIA) of This DOT

6 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 Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[1]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the oxidation of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the oxidation of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[9]
DNCB	DMDTVYC	Phase 2	DNCB increases the oxidation of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[21]
Diamide	DMOCQ9J	Investigative	Diamide increases the oxidation of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[9]

28 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 Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[10]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[11]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[13]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[14]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[15]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[16]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[17]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[7]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[18]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[19]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[20]
Celastrol	DMWQIJX	Preclinical	Celastrol decreases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[24]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[25]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[7]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[26]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[27]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[28]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF).	[29]

References

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