Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8R922G)

• DOT Name: Asparagine synthetase (ASNS)
• Synonyms: EC 6.3.5.4; Cell cycle control protein TS11; Glutamine-dependent asparagine synthetase
• Gene Name: ASNS
• Related Disease: Congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome
• UniProt ID: ASNS_HUMAN
• PDB ID: 6GQ3
• EC Number: 6.3.5.4
• Pfam ID: PF00733 ; PF13537
• Sequence:
  MCGIWALFGSDDCLSVQCLSAMKIAHRGPDAFRFENVNGYTNCCFGFHRLAVVDPLFGMQ
  PIRVKKYPYLWLCYNGEIYNHKKMQQHFEFEYQTKVDGEIILHLYDKGGIEQTICMLDGV
  FAFVLLDTANKKVFLGRDTYGVRPLFKAMTEDGFLAVCSEAKGLVTLKHSATPFLKVEPF
  LPGHYEVLDLKPNGKVASVEMVKYHHCRDVPLHALYDNVEKLFPGFEIETVKNNLRILFN
  NAVKKRLMTDRRIGCLLSGGLDSSLVAATLLKQLKEAQVQYPLQTFAIGMEDSPDLLAAR
  KVADHIGSEHYEVLFNSEEGIQALDEVIFSLETYDITTVRASVGMYLISKYIRKNTDSVV
  IFSGEGSDELTQGYIYFHKAPSPEKAEEESERLLRELYLFDVLRADRTTAAHGLELRVPF
  LDHRFSSYYLSLPPEMRIPKNGIEKHLLRETFEDSNLIPKEILWRPKEAFSDGITSVKNS
  WFKILQEYVEHQVDDAMMANAAQKFPFNTPKTKEGYYYRQVFERHYPGRADWLSHYWMPK
  WINATDPSARTLTHYKSAVKA
• KEGG Pathway:
  Alanine, aspartate and glutamate metabolism (hsa00250)
  Metabolic pathways (hsa01100)
  Biosynthesis of amino acids (hsa01230)
• Reactome Pathway:
  Aspartate and asparagine metabolism (R-HSA-8963693)
  Response of EIF2AK4 (GCN2) to amino acid deficiency (R-HSA-9633012)
  Response of EIF2AK1 (HRI) to heme deficiency (R-HSA-9648895)
  ATF4 activates genes in response to endoplasmic reticulum stress (R-HSA-380994)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome	DISATWAP	Definitive	Autosomal recessive	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Asparagine synthetase (ASNS) affects the response to substance of Mitoxantrone.	[61]

91 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 Asparagine synthetase (ASNS).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Asparagine synthetase (ASNS).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Asparagine synthetase (ASNS).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Asparagine synthetase (ASNS).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Asparagine synthetase (ASNS).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Asparagine synthetase (ASNS).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Asparagine synthetase (ASNS).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Asparagine synthetase (ASNS).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Asparagine synthetase (ASNS).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Asparagine synthetase (ASNS).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Asparagine synthetase (ASNS).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Asparagine synthetase (ASNS).	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Asparagine synthetase (ASNS).	[14]
Marinol	DM70IK5	Approved	Marinol affects the expression of Asparagine synthetase (ASNS).	[15]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Asparagine synthetase (ASNS).	[16]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Asparagine synthetase (ASNS).	[17]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Asparagine synthetase (ASNS).	[18]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Asparagine synthetase (ASNS).	[19]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Asparagine synthetase (ASNS).	[20]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Asparagine synthetase (ASNS).	[21]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Asparagine synthetase (ASNS).	[22]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Asparagine synthetase (ASNS).	[23]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Asparagine synthetase (ASNS).	[24]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Asparagine synthetase (ASNS).	[14]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Asparagine synthetase (ASNS).	[14]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Asparagine synthetase (ASNS).	[25]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Asparagine synthetase (ASNS).	[26]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Asparagine synthetase (ASNS).	[27]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Asparagine synthetase (ASNS).	[28]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Asparagine synthetase (ASNS).	[29]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Asparagine synthetase (ASNS).	[30]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Asparagine synthetase (ASNS).	[31]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Asparagine synthetase (ASNS).	[31]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Asparagine synthetase (ASNS).	[32]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Asparagine synthetase (ASNS).	[31]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Asparagine synthetase (ASNS).	[31]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Asparagine synthetase (ASNS).	[33]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Asparagine synthetase (ASNS).	[31]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Asparagine synthetase (ASNS).	[34]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Asparagine synthetase (ASNS).	[35]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Asparagine synthetase (ASNS).	[17]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Asparagine synthetase (ASNS).	[32]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Asparagine synthetase (ASNS).	[14]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of Asparagine synthetase (ASNS).	[36]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Asparagine synthetase (ASNS).	[28]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil decreases the expression of Asparagine synthetase (ASNS).	[31]
Sertraline	DM0FB1J	Approved	Sertraline increases the expression of Asparagine synthetase (ASNS).	[28]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Asparagine synthetase (ASNS).	[14]
Bexarotene	DMOBIKY	Approved	Bexarotene decreases the expression of Asparagine synthetase (ASNS).	[37]
Ampicillin	DMHWE7P	Approved	Ampicillin decreases the expression of Asparagine synthetase (ASNS).	[38]
Tetracycline	DMZA017	Approved	Tetracycline increases the expression of Asparagine synthetase (ASNS).	[17]
Thioridazine	DM35M8J	Approved	Thioridazine increases the expression of Asparagine synthetase (ASNS).	[17]
Imipramine	DM2NUH3	Approved	Imipramine increases the expression of Asparagine synthetase (ASNS).	[28]
Clomipramine	DMINRKW	Approved	Clomipramine increases the expression of Asparagine synthetase (ASNS).	[17]
Erythromycin	DM4K7GQ	Approved	Erythromycin decreases the expression of Asparagine synthetase (ASNS).	[17]
Loratadine	DMF3AN7	Approved	Loratadine increases the expression of Asparagine synthetase (ASNS).	[28]
Pentamidine	DMHZJCG	Approved	Pentamidine increases the expression of Asparagine synthetase (ASNS).	[28]
Quinidine	DMLPICK	Approved	Quinidine increases the expression of Asparagine synthetase (ASNS).	[28]
Flecainide	DMSQDLE	Approved	Flecainide increases the expression of Asparagine synthetase (ASNS).	[28]
Perhexiline	DMINO7Z	Approved	Perhexiline increases the expression of Asparagine synthetase (ASNS).	[17]
Doxepin	DMPI98T	Approved	Doxepin increases the expression of Asparagine synthetase (ASNS).	[39]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Asparagine synthetase (ASNS).	[40]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Asparagine synthetase (ASNS).	[12]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Asparagine synthetase (ASNS).	[41]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine increases the expression of Asparagine synthetase (ASNS).	[17]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Asparagine synthetase (ASNS).	[8]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Asparagine synthetase (ASNS).	[17]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Asparagine synthetase (ASNS).	[12]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Asparagine synthetase (ASNS).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Asparagine synthetase (ASNS).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Asparagine synthetase (ASNS).	[42]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Asparagine synthetase (ASNS).	[43]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Asparagine synthetase (ASNS).	[45]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Asparagine synthetase (ASNS).	[46]
ZIMELIDINE	DMNI3U2	Withdrawn from market	ZIMELIDINE increases the expression of Asparagine synthetase (ASNS).	[28]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Asparagine synthetase (ASNS).	[47]
Nobiletin	DM7R3B6	Preclinical	Nobiletin increases the expression of Asparagine synthetase (ASNS).	[48]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Asparagine synthetase (ASNS).	[49]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Asparagine synthetase (ASNS).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Asparagine synthetase (ASNS).	[50]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Asparagine synthetase (ASNS).	[51]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Asparagine synthetase (ASNS).	[52]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Asparagine synthetase (ASNS).	[53]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Asparagine synthetase (ASNS).	[32]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Asparagine synthetase (ASNS).	[54]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Asparagine synthetase (ASNS).	[55]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Asparagine synthetase (ASNS).	[56]
D-glucose	DMMG2TO	Investigative	D-glucose affects the expression of Asparagine synthetase (ASNS).	[57]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Asparagine synthetase (ASNS).	[58]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID increases the expression of Asparagine synthetase (ASNS).	[59]
N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE	DM2D4KY	Investigative	N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE increases the expression of Asparagine synthetase (ASNS).	[60]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Asparagine synthetase (ASNS).	[44]

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