Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4ZMG0Q)

• DOT Name: Argininosuccinate synthase (ASS1)
• Synonyms: EC 6.3.4.5; Citrulline--aspartate ligase
• Gene Name: ASS1
• Related Disease:
  Argininosuccinate synthase deficiency
  Citrullinemia
  Acute myelogenous leukaemia
  Adult glioblastoma
  Advanced cancer
  Argininosuccinic aciduria
  Arteriosclerosis
  Atherosclerosis
  Bladder cancer
  Bone osteosarcoma
  Breast cancer
  Clear cell renal carcinoma
  Colorectal neoplasm
  Endometrial carcinoma
  Epithelial ovarian cancer
  Glioblastoma multiforme
  Inborn error of metabolism
  Intellectual disability
  Leukemia
  Liver failure
  Lung cancer
  Malignant pleural mesothelioma
  Melanoma
  Mesothelioma
  Metabolic disorder
  Nasopharyngeal carcinoma
  Non-small-cell lung cancer
  Osteosarcoma
  Small lymphocytic lymphoma
  Small-cell lung cancer
  Systemic lupus erythematosus
  Urinary bladder cancer
  Urinary bladder neoplasm
  Uveitis
  Colorectal carcinoma
  Lung carcinoma
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Acute neonatal citrullinemia type I
  Adult-onset citrullinemia type I
  Gastric cancer
  Lymphoma
  Matthew-Wood syndrome
  Pancreatic cancer
  Stomach cancer
  Urea cycle disorder
• UniProt ID: ASSY_HUMAN
• PDB ID: 2NZ2
• EC Number: 6.3.4.5
• Pfam ID: PF20979 ; PF00764
• Sequence:
  MSSKGSVVLAYSGGLDTSCILVWLKEQGYDVIAYLANIGQKEDFEEARKKALKLGAKKVF
  IEDVSREFVEEFIWPAIQSSALYEDRYLLGTSLARPCIARKQVEIAQREGAKYVSHGATG
  KGNDQVRFELSCYSLAPQIKVIAPWRMPEFYNRFKGRNDLMEYAKQHGIPIPVTPKNPWS
  MDENLMHISYEAGILENPKNQAPPGLYTKTQDPAKAPNTPDILEIEFKKGVPVKVTNVKD
  GTTHQTSLELFMYLNEVAGKHGVGRIDIVENRFIGMKSRGIYETPAGTILYHAHLDIEAF
  TMDREVRKIKQGLGLKFAELVYTGFWHSPECEFVRHCIAKSQERVEGKVQVSVLKGQVYI
  LGRESPLSLYNEELVSMNVQGDYEPTDATGFININSLRLKEYHRLQSKVTAK
• Function: One of the enzymes of the urea cycle, the metabolic pathway transforming neurotoxic amonia produced by protein catabolism into inocuous urea in the liver of ureotelic animals. Catalyzes the formation of arginosuccinate from aspartate, citrulline and ATP and together with ASL it is responsible for the biosynthesis of arginine in most body tissues.
• Tissue Specificity: Expressed in adult liver.
• KEGG Pathway:
  Arginine biosynthesis (hsa00220)
  Alanine, aspartate and glutamate metabolism (hsa00250)
  Metabolic pathways (hsa01100)
  Biosynthesis of amino acids (hsa01230)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway: Urea cycle (R-HSA-70635)
• BioCyc Pathway: MetaCyc:HS05425-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Argininosuccinate synthase deficiency	DIS6MQUG	Definitive	Autosomal recessive	[1]
Citrullinemia	DISX1GZ8	Definitive	Genetic Variation	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Argininosuccinic aciduria	DIS141BY	Strong	Biomarker	[6]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[7]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[7]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[8]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[9]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[12]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[13]
Epithelial ovarian cancer	DIS56MH2	Strong	Posttranslational Modification	[14]
Glioblastoma multiforme	DISK8246	Strong	Posttranslational Modification	[15]
Inborn error of metabolism	DISO5FAY	Strong	Biomarker	[16]
Intellectual disability	DISMBNXP	Strong	Biomarker	[17]
Leukemia	DISNAKFL	Strong	Altered Expression	[18]
Liver failure	DISLGEL6	Strong	Biomarker	[19]
Lung cancer	DISCM4YA	Strong	Biomarker	[20]
Malignant pleural mesothelioma	DIST2R60	Strong	Biomarker	[21]
Melanoma	DIS1RRCY	Strong	Altered Expression	[22]
Mesothelioma	DISKWK9M	Strong	Biomarker	[23]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[24]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[25]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[21]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[9]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[26]
Small-cell lung cancer	DISK3LZD	Strong	Altered Expression	[27]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[28]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[8]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[8]
Uveitis	DISV0RYS	Strong	Biomarker	[29]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[30]
Lung carcinoma	DISTR26C	moderate	Biomarker	[20]
Ovarian cancer	DISZJHAP	moderate	Posttranslational Modification	[14]
Ovarian neoplasm	DISEAFTY	moderate	Posttranslational Modification	[14]
Prostate cancer	DISF190Y	moderate	Biomarker	[31]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[31]
Renal cell carcinoma	DISQZ2X8	moderate	Biomarker	[11]
Acute neonatal citrullinemia type I	DISQC3Q0	Supportive	Autosomal recessive	[32]
Adult-onset citrullinemia type I	DISSA99C	Supportive	Autosomal recessive	[32]
Gastric cancer	DISXGOUK	Limited	Biomarker	[33]
Lymphoma	DISN6V4S	Limited	Altered Expression	[34]
Matthew-Wood syndrome	DISA7HR7	Limited	Altered Expression	[25]
Pancreatic cancer	DISJC981	Limited	Biomarker	[35]
Stomach cancer	DISKIJSX	Limited	Biomarker	[33]
Urea cycle disorder	DIS5O5V0	Limited	Altered Expression	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Argininosuccinate synthase (ASS1) affects the response to substance of Topotecan.	[64]
Mitoxantrone	DMM39BF	Approved	Argininosuccinate synthase (ASS1) affects the response to substance of Mitoxantrone.	[64]

30 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 Argininosuccinate synthase (ASS1).	[37]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Argininosuccinate synthase (ASS1).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Argininosuccinate synthase (ASS1).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Argininosuccinate synthase (ASS1).	[40]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Argininosuccinate synthase (ASS1).	[41]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Argininosuccinate synthase (ASS1).	[42]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Argininosuccinate synthase (ASS1).	[43]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Argininosuccinate synthase (ASS1).	[39]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Argininosuccinate synthase (ASS1).	[44]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Argininosuccinate synthase (ASS1).	[45]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Argininosuccinate synthase (ASS1).	[46]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Argininosuccinate synthase (ASS1).	[47]
Selenium	DM25CGV	Approved	Selenium increases the expression of Argininosuccinate synthase (ASS1).	[48]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Argininosuccinate synthase (ASS1).	[44]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Argininosuccinate synthase (ASS1).	[49]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Argininosuccinate synthase (ASS1).	[50]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Argininosuccinate synthase (ASS1).	[51]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Argininosuccinate synthase (ASS1).	[52]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Argininosuccinate synthase (ASS1).	[44]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Argininosuccinate synthase (ASS1).	[53]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Argininosuccinate synthase (ASS1).	[41]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Argininosuccinate synthase (ASS1).	[56]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Argininosuccinate synthase (ASS1).	[57]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Argininosuccinate synthase (ASS1).	[37]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Argininosuccinate synthase (ASS1).	[58]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Argininosuccinate synthase (ASS1).	[59]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Argininosuccinate synthase (ASS1).	[60]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Argininosuccinate synthase (ASS1).	[61]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Argininosuccinate synthase (ASS1).	[62]
AM251	DMTAWHL	Investigative	AM251 increases the expression of Argininosuccinate synthase (ASS1).	[63]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Argininosuccinate synthase (ASS1).	[54]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Argininosuccinate synthase (ASS1).	[55]

References

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