Details of Drug Off-Target (DOT)

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

• DOT Name: Adenylosuccinate lyase (ADSL)
• Synonyms: ADSL; ASL; EC 4.3.2.2; Adenylosuccinase; ASase
• Gene Name: ADSL
• Related Disease:
  Adenylosuccinate lyase deficiency
  Metabolic disorder
  Molybdenum cofactor deficiency
  Phosphoribosylpyrophosphate synthetase superactivity
  Argininosuccinic aciduria
  Chronic graft versus host disease
  Dementia
  Endometrial cancer
  Endometrial carcinoma
  Inborn error of metabolism
  Intellectual disability
  Major depressive disorder
  Meningeal tuberculosis
  Triple negative breast cancer
  Autism
  Breast cancer
  Nervous system disease
• UniProt ID: PUR8_HUMAN
• PDB ID: 2J91; 2VD6; 4FFX; 4FLC
• EC Number: 4.3.2.2
• Pfam ID: PF10397 ; PF00206
• Sequence:
  MAAGGDHGSPDSYRSPLASRYASPEMCFVFSDRYKFRTWRQLWLWLAEAEQTLGLPITDE
  QIQEMKSNLENIDFKMAAEEEKRLRHDVMAHVHTFGHCCPKAAGIIHLGATSCYVGDNTD
  LIILRNALDLLLPKLARVISRLADFAKERASLPTLGFTHFQPAQLTTVGKRCCLWIQDLC
  MDLQNLKRVRDDLRFRGVKGTTGTQASFLQLFEGDDHKVEQLDKMVTEKAGFKRAFIITG
  QTYTRKVDIEVLSVLASLGASVHKICTDIRLLANLKEMEEPFEKQQIGSSAMPYKRNPMR
  SERCCSLARHLMTLVMDPLQTASVQWFERTLDDSANRRICLAEAFLTADTILNTLQNISE
  GLVVYPKVIERRIRQELPFMATENIIMAMVKAGGSRQDCHEKIRVLSQQAASVVKQEGGD
  NDLIERIQVDAYFSPIHSQLDHLLDPSSFTGRASQQVQRFLEEEVYPLLKPYESVMKVKA
  ELCL
• Function: Catalyzes two non-sequential steps in de novo AMP synthesis: converts (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate (SAICAR) to fumarate plus 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide, and thereby also contributes to de novo IMP synthesis, and converts succinyladenosine monophosphate (SAMP) to AMP and fumarate.
• Tissue Specificity: Ubiquitously expressed. Both isoforms are produced by all tissues. Isoform 2 is 10-fold less abundant than isoform 1.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Alanine, aspartate and glutamate metabolism (hsa00250)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)
• BioCyc Pathway: MetaCyc:HS02059-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenylosuccinate lyase deficiency	DIS6XHJX	Definitive	Autosomal recessive	[1]
Metabolic disorder	DIS71G5H	Definitive	Biomarker	[2]
Molybdenum cofactor deficiency	DISKS8QN	Definitive	Altered Expression	[3]
Phosphoribosylpyrophosphate synthetase superactivity	DISD5WC1	Definitive	Biomarker	[3]
Argininosuccinic aciduria	DIS141BY	Strong	Altered Expression	[4]
Chronic graft versus host disease	DIS1MM9J	Strong	Biomarker	[5]
Dementia	DISXL1WY	Strong	Biomarker	[6]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[7]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[7]
Inborn error of metabolism	DISO5FAY	Strong	Biomarker	[8]
Intellectual disability	DISMBNXP	Strong	Biomarker	[9]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[10]
Meningeal tuberculosis	DIS8KHDE	Strong	Biomarker	[11]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[12]
Autism	DISV4V1Z	Limited	Biomarker	[4]
Breast cancer	DIS7DPX1	Limited	Biomarker	[13]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[14]

12 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 Adenylosuccinate lyase (ADSL).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Adenylosuccinate lyase (ADSL).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Adenylosuccinate lyase (ADSL).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Adenylosuccinate lyase (ADSL).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Adenylosuccinate lyase (ADSL).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Adenylosuccinate lyase (ADSL).	[20]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Adenylosuccinate lyase (ADSL).	[21]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Adenylosuccinate lyase (ADSL).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Adenylosuccinate lyase (ADSL).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Adenylosuccinate lyase (ADSL).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Adenylosuccinate lyase (ADSL).	[27]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Adenylosuccinate lyase (ADSL).	[28]

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 Adenylosuccinate lyase (ADSL).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Adenylosuccinate lyase (ADSL).	[26]

References

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• [12] Prolyl hydroxylase substrate adenylosuccinate lyase is an oncogenic driver in triple negative breast cancer.Nat Commun. 2019 Nov 15;10(1):5177. doi: 10.1038/s41467-019-13168-4.
• [13] A comparison of succinyladenylate lyase activity and serum sialic acid as markers of malignancy.Biochem Med. 1985 Dec;34(3):327-34. doi: 10.1016/0006-2944(85)90095-x.
• [14] Inhibition of defective adenylosuccinate lyase by HNE: a neurological disease that may be affected by oxidative stress.Biofactors. 2005;24(1-4):131-6. doi: 10.1002/biof.5520240115.
• [15] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [16] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [17] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
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• [21] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [22] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
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