Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHY8SY4)

DOT Name	DNA damage-inducible transcript 4 protein (DDIT4)
Synonyms	HIF-1 responsive protein RTP801; Protein regulated in development and DNA damage response 1; REDD-1
Gene Name	DDIT4
UniProt ID	DDIT4_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3LQ9; 7MOP
Pfam ID	PF07809
Sequence	MPSLWDRFSSSSTSSSPSSLPRTPTPDRPPRSAWGSATREEGFDRSTSLESSDCESLDSS NSGFGPEEDTAYLDGVSLPDFELLSDPEDEHLCANLMQLLQESLAQARLGSRRPARLLMP SQLVSQVGKELLRLAYSEPCGLRGALLDVCVEQGKSCHSVGQLALDPSLVPTFQLTLVLR LDSRLWPKIQGLFSSANSPFLPGFSQSLTLSTGFRVIKKKLYSSEQLLIEEC
Function	Regulates cell growth, proliferation and survival via inhibition of the activity of the mammalian target of rapamycin complex 1 (mTORC1). Inhibition of mTORC1 is mediated by a pathway that involves DDIT4/REDD1, AKT1, the TSC1-TSC2 complex and the GTPase RHEB. Plays an important role in responses to cellular energy levels and cellular stress, including responses to hypoxia and DNA damage. Regulates p53/TP53-mediated apoptosis in response to DNA damage via its effect on mTORC1 activity. Its role in the response to hypoxia depends on the cell type; it mediates mTORC1 inhibition in fibroblasts and thymocytes, but not in hepatocytes. Required for mTORC1-mediated defense against viral protein synthesis and virus replication. Inhibits neuronal differentiation and neurite outgrowth mediated by NGF via its effect on mTORC1 activity. Required for normal neuron migration during embryonic brain development. Plays a role in neuronal cell death.
Tissue Specificity	Broadly expressed, with lowest levels in brain, skeletal muscle and intestine. Up-regulated in substantia nigra neurons from Parkinson disease patients (at protein level).
KEGG Pathway	Autophagy - animal (hsa04140 ) mTOR sig.ling pathway (hsa04150 ) PI3K-Akt sig.ling pathway (hsa04151 ) MicroR.s in cancer (hsa05206 )
Reactome Pathway	TP53 Regulates Metabolic Genes (R-HSA-5628897 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	DNA damage-inducible transcript 4 protein (DDIT4) affects the response to substance of Etoposide.	[61]
Mitomycin	DMH0ZJE	Approved	DNA damage-inducible transcript 4 protein (DDIT4) affects the response to substance of Mitomycin.	[61]
Topotecan	DMP6G8T	Approved	DNA damage-inducible transcript 4 protein (DDIT4) affects the response to substance of Topotecan.	[61]
Mitoxantrone	DMM39BF	Approved	DNA damage-inducible transcript 4 protein (DDIT4) affects the response to substance of Mitoxantrone.	[61]
Cyclophosphamide	DM4O2Z7	Approved	DNA damage-inducible transcript 4 protein (DDIT4) affects the response to substance of Cyclophosphamide.	[61]
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71 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 DNA damage-inducible transcript 4 protein (DDIT4).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[12]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[13]
Marinol	DM70IK5	Approved	Marinol decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[15]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[16]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[17]
Menadione	DMSJDTY	Approved	Menadione affects the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[18]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[19]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[20]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[21]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[22]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[23]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[24]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[25]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[26]
Cidofovir	DMA13GD	Approved	Cidofovir affects the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[15]
Gemcitabine	DMSE3I7	Approved	Gemcitabine affects the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[27]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[15]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[28]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[15]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[15]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[29]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[30]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[30]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[6]
Sorafenib	DMS8IFC	Approved	Sorafenib increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[31]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[32]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[6]
Orlistat	DMRJSP8	Approved	Orlistat increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[33]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[34]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[35]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[36]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[37]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[39]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[40]
LY294002	DMY1AFS	Phase 1	LY294002 decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[41]
Arecoline	DMFJZK3	Phase 1	Arecoline increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[42]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[43]
T83193	DMHO29Y	Patented	T83193 increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[44]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[45]
HELENALIN	DMMCI4H	Terminated	HELENALIN increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[47]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[48]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[49]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[50]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[51]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[52]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[53]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[54]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[55]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[56]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[9]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[12]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[44]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[57]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[52]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[58]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[59]
AM251	DMTAWHL	Investigative	AM251 increases the expression of DNA damage-inducible transcript 4 protein (DDIT4).	[60]
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⏷ Show the Full List of 71 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the ubiquitination of DNA damage-inducible transcript 4 protein (DDIT4).	[8]
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