Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHJ9MCZ)

• DOT Name: Diablo IAP-binding mitochondrial protein (DIABLO)
• Synonyms: Diablo homolog, mitochondrial; Direct IAP-binding protein with low pI; Second mitochondria-derived activator of caspase; Smac
• Gene Name: DIABLO
• Related Disease:
  Autosomal dominant nonsyndromic hearing loss 64
  Autosomal dominant nonsyndromic hearing loss
  Nonsyndromic genetic hearing loss
• UniProt ID: DBLOH_HUMAN
• PDB ID: 1FEW; 1G3F; 1G73; 1OXQ; 1TW6; 1XB0; 1XB1; 3D9U; 3UIH; 3UIJ; 4TX5; 6JX6; 8ATO; 8AUW; 8E2I; 8E2J
• Pfam ID: PF09057
• Sequence:
  MAALKSWLSRSVTSFFRYRQCLCVPVVANFKKRCFSELIRPWHKTVTIGFGVTLCAVPIA
  QKSEPHSLSSEALMRRAVSLVTDSTSTFLSQTTYALIEAITEYTKAVYTLTSLYRQYTSL
  LGKMNSEEEDEVWQVIIGARAEMTSKHQEYLKLETTWMTAVGLSEMAAEAAYQTGADQAS
  ITARNHIQLVKLQVEEVHQLSRKAETKLAEAQIEELRQKTQEEGEERAESEQEAYLRED
• Function: Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases; [Isoform 3]: Attenuates the stability and apoptosis-inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation; [Isoform 1]: Defective in the capacity to down-regulate the XIAP/BIRC4 abundance.
• Tissue Specificity: Ubiquitously expressed with highest expression in testis. Expression is also high in heart, liver, kidney, spleen, prostate and ovary. Low in brain, lung, thymus and peripheral blood leukocytes. Isoform 3 is ubiquitously expressed.
• KEGG Pathway:
  Apoptosis (hsa04210)
  Apoptosis - multiple species (hsa04215)
• Reactome Pathway:
  SMAC (DIABLO) binds to IAPs (R-HSA-111463)
  SMAC(DIABLO)-mediated dissociation of IAP (R-HSA-111464)
  SMAC, XIAP-regulated apoptotic response (R-HSA-111469)
  Regulation of the apoptosome activity (R-HSA-9627069)
  Release of apoptotic factors from the mitochondria (R-HSA-111457)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal dominant nonsyndromic hearing loss 64	DISX8RZZ	Moderate	Autosomal dominant	[1]
Autosomal dominant nonsyndromic hearing loss	DISYC1G0	Supportive	Autosomal dominant	[1]
Nonsyndromic genetic hearing loss	DISZX61P	Limited	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Diablo IAP-binding mitochondrial protein (DIABLO) increases the response to substance of Cisplatin.	[42]
PEITC	DMOMN31	Phase 2	Diablo IAP-binding mitochondrial protein (DIABLO) affects the binding of PEITC.	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[10]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[11]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[13]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[14]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[15]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[4]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[17]
Melatonin	DMKWFBT	Approved	Melatonin increases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[21]
Adenosine	DMM2NSK	Approved	Adenosine increases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[22]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[26]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[28]
Dioscin	DM5H2W9	Preclinical	Dioscin increases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[32]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[33]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[34]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[36]
(E)-4-(3,5-dimethoxystyryl)phenol	DMYXI2V	Investigative	(E)-4-(3,5-dimethoxystyryl)phenol increases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[38]
Morin	DM2OGZ5	Investigative	Morin increases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[39]
Corosolic acid	DM563PZ	Investigative	Corosolic acid decreases the expression of Diablo IAP-binding mitochondrial protein (DIABLO).	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Dexamethasone	DMMWZET	Approved	Dexamethasone affects the localization of Diablo IAP-binding mitochondrial protein (DIABLO).	[12]
Dasatinib	DMJV2EK	Approved	Dasatinib affects the localization of Diablo IAP-binding mitochondrial protein (DIABLO).	[16]
Simvastatin	DM30SGU	Approved	Simvastatin affects the localization of Diablo IAP-binding mitochondrial protein (DIABLO).	[18]
Sorafenib	DMS8IFC	Approved	Sorafenib affects the localization of Diablo IAP-binding mitochondrial protein (DIABLO).	[19]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide affects the localization of Diablo IAP-binding mitochondrial protein (DIABLO).	[20]
Bendamustine hydrochloride	DMFH15Z	Approved	Bendamustine hydrochloride increases the localization of Diablo IAP-binding mitochondrial protein (DIABLO).	[23]
Resveratrol	DM3RWXL	Phase 3	Resveratrol affects the localization of Diablo IAP-binding mitochondrial protein (DIABLO).	[24]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate affects the localization of Diablo IAP-binding mitochondrial protein (DIABLO).	[25]
Flavopiridol	DMKSUOI	Phase 2	Flavopiridol affects the localization of Diablo IAP-binding mitochondrial protein (DIABLO).	[27]
AEW-541	DMQF982	Phase 1	AEW-541 affects the localization of Diablo IAP-binding mitochondrial protein (DIABLO).	[16]
Spermine	DMD4BFY	Terminated	Spermine affects the localization of Diablo IAP-binding mitochondrial protein (DIABLO).	[30]
F-12509A	DM3786U	Terminated	F-12509A affects the localization of Diablo IAP-binding mitochondrial protein (DIABLO).	[31]
Paraquat	DMR8O3X	Investigative	Paraquat increases the transport of Diablo IAP-binding mitochondrial protein (DIABLO).	[35]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde affects the localization of Diablo IAP-binding mitochondrial protein (DIABLO).	[37]
BADGE	DMCK5DG	Investigative	BADGE affects the localization of Diablo IAP-binding mitochondrial protein (DIABLO).	[40]

References

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