Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLGH7EW)

• DOT Name: Brain-derived neurotrophic factor (BDNF)
• Synonyms: BDNF; Abrineurin
• Gene Name: BDNF
• UniProt ID: BDNF_HUMAN
• PDB ID: 1B8M; 1BND
• Pfam ID: PF00243
• Sequence:
  MTILFLTMVISYFGCMKAAPMKEANIRGQGGLAYPGVRTHGTLESVNGPKAGSRGLTSLA
  DTFEHVIEELLDEDQKVRPNEENNKDADLYTSRVMLSSQVPLEPPLLFLLEEYKNYLDAA
  NMSMRVRRHSDPARRGELSVCDSISEWVTAADKKTAVDMSGGTVTVLEKVPVSKGQLKQY
  FYETKCNPMGYTKEGCRGIDKRHWNSQCRTTQSYVRALTMDSKKRIGWRFIRIDTSCVCT
  LTIKRGR
• Function: Important signaling molecule that activates signaling cascades downstream of NTRK2. During development, promotes the survival and differentiation of selected neuronal populations of the peripheral and central nervous systems. Participates in axonal growth, pathfinding and in the modulation of dendritic growth and morphology. Major regulator of synaptic transmission and plasticity at adult synapses in many regions of the CNS. The versatility of BDNF is emphasized by its contribution to a range of adaptive neuronal responses including long-term potentiation (LTP), long-term depression (LTD), certain forms of short-term synaptic plasticity, as well as homeostatic regulation of intrinsic neuronal excitability; [BDNF precursor form]: Important signaling molecule that activates signaling cascades downstream of NTRK2. Activates signaling cascades via the heterodimeric receptor formed by NGFR and SORCS2. Signaling via NGFR and SORCS2 plays a role in synaptic plasticity and long-term depression (LTD). Binding to NGFR and SORCS2 promotes neuronal apoptosis. Promotes neuronal growth cone collapse.
• Tissue Specificity: Detected in blood plasma and in saliva (at protein level) . Brain. Highly expressed in hippocampus, amygdala, cerebral cortex and cerebellum. Also expressed in heart, lung, skeletal muscle, testis, prostate and placenta.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  cAMP sig.ling pathway (hsa04024)
  PI3K-Akt sig.ling pathway (hsa04151)
  Neurotrophin sig.ling pathway (hsa04722)
  Huntington disease (hsa05016)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Cocaine addiction (hsa05030)
  Alcoholism (hsa05034)
• Reactome Pathway:
  BDNF activates NTRK2 (TRKB) signaling (R-HSA-9024909)
  Activated NTRK2 signals through RAS (R-HSA-9026519)
  Activated NTRK2 signals through PLCG1 (R-HSA-9026527)
  Activated NTRK2 signals through PI3K (R-HSA-9028335)
  Activated NTRK2 signals through FRS2 and FRS3 (R-HSA-9028731)
  Activated NTRK2 signals through FYN (R-HSA-9032500)
  NTRK2 activates RAC1 (R-HSA-9032759)
  Activated NTRK2 signals through CDK5 (R-HSA-9032845)
  NPAS4 regulates expression of target genes (R-HSA-9768919)
  MECP2 regulates transcription of neuronal ligands (R-HSA-9022702)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cocaine	DMSOX7I	Approved	Brain-derived neurotrophic factor (BDNF) decreases the response to substance of Cocaine.	[41]
Methamphetamine	DMPM4SK	Approved	Brain-derived neurotrophic factor (BDNF) increases the response to substance of Methamphetamine.	[42]
Fluoxetine	DM3PD2C	Approved	Brain-derived neurotrophic factor (BDNF) increases the response to substance of Fluoxetine.	[43]
Dextroamphetamine	DMMIHVP	Approved	Brain-derived neurotrophic factor (BDNF) affects the response to substance of Dextroamphetamine.	[45]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Brain-derived neurotrophic factor (BDNF) affects the response to substance of Chlorpromazine.	[46]
Lithium	DMZ3OU6	Phase 2	Brain-derived neurotrophic factor (BDNF) increases the response to substance of Lithium.	[47]

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Nitric Oxide	DM1RBYG	Approved	Brain-derived neurotrophic factor (BDNF) increases the chemical synthesis of Nitric Oxide.	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Brain-derived neurotrophic factor (BDNF).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Brain-derived neurotrophic factor (BDNF).	[2]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Brain-derived neurotrophic factor (BDNF).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Brain-derived neurotrophic factor (BDNF).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Brain-derived neurotrophic factor (BDNF).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Brain-derived neurotrophic factor (BDNF).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Brain-derived neurotrophic factor (BDNF).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Brain-derived neurotrophic factor (BDNF).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Brain-derived neurotrophic factor (BDNF).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Brain-derived neurotrophic factor (BDNF).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Brain-derived neurotrophic factor (BDNF).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Brain-derived neurotrophic factor (BDNF).	[10]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Brain-derived neurotrophic factor (BDNF).	[11]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Brain-derived neurotrophic factor (BDNF).	[5]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Brain-derived neurotrophic factor (BDNF).	[12]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Brain-derived neurotrophic factor (BDNF).	[13]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Brain-derived neurotrophic factor (BDNF).	[14]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Brain-derived neurotrophic factor (BDNF).	[17]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Brain-derived neurotrophic factor (BDNF).	[18]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Brain-derived neurotrophic factor (BDNF).	[19]
Haloperidol	DM96SE0	Approved	Haloperidol increases the expression of Brain-derived neurotrophic factor (BDNF).	[20]
Olanzapine	DMPFN6Y	Approved	Olanzapine increases the expression of Brain-derived neurotrophic factor (BDNF).	[20]
Heroin diacetylmorphine	DMDBWHY	Approved	Heroin diacetylmorphine decreases the expression of Brain-derived neurotrophic factor (BDNF).	[21]
Bupivacaine	DM4PRFC	Approved	Bupivacaine decreases the expression of Brain-derived neurotrophic factor (BDNF).	[23]
Cabergoline	DMQ4HIN	Approved	Cabergoline increases the expression of Brain-derived neurotrophic factor (BDNF).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Brain-derived neurotrophic factor (BDNF).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Brain-derived neurotrophic factor (BDNF).	[26]
PF-3758309	DM36PKZ	Phase 1	PF-3758309 increases the expression of Brain-derived neurotrophic factor (BDNF).	[28]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Brain-derived neurotrophic factor (BDNF).	[29]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Brain-derived neurotrophic factor (BDNF).	[31]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Brain-derived neurotrophic factor (BDNF).	[32]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Brain-derived neurotrophic factor (BDNF).	[33]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Brain-derived neurotrophic factor (BDNF).	[34]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Brain-derived neurotrophic factor (BDNF).	[35]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Brain-derived neurotrophic factor (BDNF).	[36]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Brain-derived neurotrophic factor (BDNF).	[37]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of Brain-derived neurotrophic factor (BDNF).	[38]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the expression of Brain-derived neurotrophic factor (BDNF).	[39]
methylglyoxal	DMRC3OZ	Investigative	methylglyoxal increases the expression of Brain-derived neurotrophic factor (BDNF).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Nicotine	DMWX5CO	Approved	Nicotine increases the secretion of Brain-derived neurotrophic factor (BDNF).	[15]
Malathion	DMXZ84M	Approved	Malathion decreases the secretion of Brain-derived neurotrophic factor (BDNF).	[16]
Clopidogrel	DMOL54H	Approved	Clopidogrel decreases the secretion of Brain-derived neurotrophic factor (BDNF).	[22]

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