Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8VACT2)

DOT Name	Arylacetamide deacetylase (AADAC)
Synonyms	EC 3.1.1.3
Gene Name	AADAC
Related Disease	Neuroblastoma ( ) Acute monocytic leukemia ( ) Acute myelogenous leukaemia ( ) Advanced cancer ( ) Bladder cancer ( ) Bone osteosarcoma ( ) Breast cancer ( ) Breast carcinoma ( ) Cholangiocarcinoma ( ) Clear cell renal carcinoma ( ) Cutaneous leishmaniasis ( ) Dorfman-Chanarin disease ( ) Esophageal squamous cell carcinoma ( ) Fatty liver disease ( ) Hepatocellular carcinoma ( ) HIV infectious disease ( ) Liver cirrhosis ( ) Malignant soft tissue neoplasm ( ) Myelodysplastic syndrome ( ) Neoplasm ( ) Osteosarcoma ( ) Relapsing-remitting multiple sclerosis ( ) Renal cell carcinoma ( ) Rhabdomyosarcoma ( ) Sarcoma ( ) Testicular cancer ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Colon cancer ( ) Colon carcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Metastatic malignant neoplasm ( ) Hemoglobinopathy ( ) Melanoma ( ) Myeloproliferative neoplasm ( ) Tourette syndrome ( )
UniProt ID	AAAD_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	3.1.1.3
Pfam ID	PF07859
Sequence	MGRKSLYLLIVGILIAYYIYTPLPDNVEEPWRMMWINAHLKTIQNLATFVELLGLHHFMD SFKVVGSFDEVPPTSDENVTVTETKFNNILVRVYVPKRKSEALRRGLFYIHGGGWCVGSA ALSGYDLLSRWTADRLDAVVVSTNYRLAPKYHFPIQFEDVYNALRWFLRKKVLAKYGVNP ERIGISGDSAGGNLAAAVTQQLLDDPDVKIKLKIQSLIYPALQPLDVDLPSYQENSNFLF LSKSLMVRFWSEYFTTDRSLEKAMLSRQHVPVESSHLFKFVNWSSLLPERFIKGHVYNNP NYGSSELAKKYPGFLDVRAAPLLADDNKLRGLPLTYVITCQYDLLRDDGLMYVTRLRNTG VQVTHNHVEDGFHGAFSFLGLKISHRLINQYIEWLKENL
Function	Displays cellular triglyceride lipase activity in liver, increases the levels of intracellular fatty acids derived from the hydrolysis of newly formed triglyceride stores and plays a role in very low-density lipoprotein assembly. Displays serine esterase activity in liver. Deacetylates a variety of arylacetamide substrates, including xenobiotic compounds and procarcinogens, converting them to the primary arylamide compounds and increasing their toxicity.
Tissue Specificity	Detected in liver (at protein level). Mainly expressed in liver, small intestine, colon, adrenal gland and bladder.
Reactome Pathway	Phase I - Functionalization of compounds (R-HSA-211945 )

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Neuroblastoma	DISVZBI4	Definitive	Biomarker	[1]
Acute monocytic leukemia	DIS28NEL	Strong	Genetic Variation	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	Strong	Biomarker	[4]
Bone osteosarcoma	DIST1004	Strong	Posttranslational Modification	[5]
Breast cancer	DIS7DPX1	Strong	Posttranslational Modification	[6]
Breast carcinoma	DIS2UE88	Strong	Posttranslational Modification	[6]
Cholangiocarcinoma	DIS71F6X	Strong	Posttranslational Modification	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[8]
Cutaneous leishmaniasis	DISRK7TS	Strong	Genetic Variation	[9]
Dorfman-Chanarin disease	DISKKT3R	Strong	Biomarker	[10]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[3]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
HIV infectious disease	DISO97HC	Strong	Biomarker	[12]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[10]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Altered Expression	[13]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Osteosarcoma	DISLQ7E2	Strong	Posttranslational Modification	[5]
Relapsing-remitting multiple sclerosis	DISSXFCF	Strong	Biomarker	[15]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[8]
Rhabdomyosarcoma	DISNR7MS	Strong	Altered Expression	[16]
Sarcoma	DISZDG3U	Strong	Altered Expression	[13]
Testicular cancer	DIS6HNYO	Strong	Altered Expression	[13]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[4]
Colon cancer	DISVC52G	moderate	Biomarker	[17]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[17]
Lung cancer	DISCM4YA	moderate	Biomarker	[17]
Lung carcinoma	DISTR26C	moderate	Biomarker	[17]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[17]
Hemoglobinopathy	DISCT4GX	Limited	Biomarker	[18]
Melanoma	DIS1RRCY	Limited	Biomarker	[19]
Myeloproliferative neoplasm	DIS5KAPA	Limited	Biomarker	[20]
Tourette syndrome	DISX9D54	No Known	Unknown	[21]
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⏷ Show the Full List of 37 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Biotransformations of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Rifampicin	DM5DSFZ	Approved	Arylacetamide deacetylase (AADAC) decreases the acetylation of Rifampicin.	[29]
Flutamide	DMK0O7U	Approved	Arylacetamide deacetylase (AADAC) increases the hydrolysis of Flutamide.	[30]
Rifapentine	DMCHV4I	Approved	Arylacetamide deacetylase (AADAC) decreases the acetylation of Rifapentine.	[29]
Phenacetin	DMRQAM0	Withdrawn from market	Arylacetamide deacetylase (AADAC) increases the hydrolysis of Phenacetin.	[30]
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1 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 Arylacetamide deacetylase (AADAC).	[22]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Arylacetamide deacetylase (AADAC).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Arylacetamide deacetylase (AADAC).	[24]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Arylacetamide deacetylase (AADAC).	[23]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Arylacetamide deacetylase (AADAC).	[25]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Arylacetamide deacetylase (AADAC).	[26]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Arylacetamide deacetylase (AADAC).	[26]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Arylacetamide deacetylase (AADAC).	[26]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Arylacetamide deacetylase (AADAC).	[27]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Arylacetamide deacetylase (AADAC).	[28]
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⏷ Show the Full List of 9 Drug(s)

References

1	Genome-wide promoter methylation analysis in neuroblastoma identifies prognostic methylation biomarkers.Genome Biol. 2012 Oct 3;13(10):R95. doi: 10.1186/gb-2012-13-10-r95.
2	Early induction intensification with cladribine, cytarabine, and mitoxantrone (CLAM) in AML patients treated with the DAC induction regimen: a prospective, non-randomized, phase II study of the Polish Adult Leukemia Group (PALG).Leuk Lymphoma. 2020 Mar;61(3):588-603. doi: 10.1080/10428194.2019.1678151. Epub 2019 Oct 29.
3	Decitabine enhances tumor recognition by T cells through upregulating the MAGE-A3 expression in esophageal carcinoma.Biomed Pharmacother. 2019 Apr;112:108632. doi: 10.1016/j.biopha.2019.108632. Epub 2019 Feb 20.
4	The epigenetically regulated effects of Wnt antagonists on the expression of genes in the apoptosis pathway in human bladder cancer cell line (T24).DNA Cell Biol. 2014 Jul;33(7):408-17. doi: 10.1089/dna.2013.2285. Epub 2014 Mar 25.
5	Activation of Estrogen Receptor Alpha by Decitabine Inhibits Osteosarcoma Growth and Metastasis.Cancer Res. 2019 Mar 15;79(6):1054-1068. doi: 10.1158/0008-5472.CAN-18-1255. Epub 2018 Dec 28.
6	Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment.PLoS One. 2011;6(11):e27355. doi: 10.1371/journal.pone.0027355. Epub 2011 Nov 4.
7	Targeted drug regulation on methylation of p53-BAX mitochondrial apoptosis pathway affects the growth of cholangiocarcinoma cells.J Int Med Res. 2012;40(1):67-75. doi: 10.1177/147323001204000107.
8	DNA methyltransferase inhibitor-mediated apoptosis in the Wnt/-catenin signal pathway in a renal cell carcinoma cell line.Exp Biol Med (Maywood). 2013 Sep;238(9):1009-16. doi: 10.1177/1535370213498984. Epub 2013 Aug 23.
9	Salvage therapy with Sodium chlorosum (formerly DAC N-055) for cases of refractory lupoid cutaneous leishmaniasis: results from a compassionate use study with 0.09% Sodium chlorosum in amphiphilic basic cream.BMC Infect Dis. 2019 Nov 28;19(1):1005. doi: 10.1186/s12879-019-4518-x.
10	Liver cirrhosis in an infant with Chanarin-Dorfman syndrome caused by a novel splice-site mutation in ABHD5.Acta Paediatr. 2010 Oct;99(10):1592-4. doi: 10.1111/j.1651-2227.2010.01869.x.
11	Upregulation of miR-362-3p Modulates Proliferation and Anchorage-Independent Growth by Directly Targeting Tob2 in Hepatocellular Carcinoma.J Cell Biochem. 2015 Aug;116(8):1563-73. doi: 10.1002/jcb.25110.
12	A Population Pharmacokinetic Analysis Shows that Arylacetamide Deacetylase (AADAC) Gene Polymorphism and HIV Infection Affect the Exposure of Rifapentine.Antimicrob Agents Chemother. 2019 Mar 27;63(4):e01964-18. doi: 10.1128/AAC.01964-18. Print 2019 Apr.
13	Decitabine facilitates immune recognition of sarcoma cells by upregulating CT antigens, MHC molecules, and ICAM-1.Tumour Biol. 2014 Jun;35(6):5753-62. doi: 10.1007/s13277-014-1764-9. Epub 2014 Mar 2.
14	Establishment and molecular characterization of decitabine-resistant K562 cells.J Cell Mol Med. 2019 May;23(5):3317-3324. doi: 10.1111/jcmm.14221. Epub 2019 Feb 22.
15	Daclizumab and its use in multiple sclerosis treatment.Drugs Today (Barc). 2017 Jan;53(1):7-18. doi: 10.1358/dot.2017.53.1.2570979.
16	Therapeutic differentiation in a human rhabdomyosarcoma cell line selected for resistance to actinomycin D.Int J Cancer. 1998 Jan 30;75(3):379-83. doi: 10.1002/(sici)1097-0215(19980130)75:3<379::aid-ijc9>3.0.co;2-#.
17	DAC can restore expression of NALP1 to suppress tumor growth in colon cancer.Cell Death Dis. 2015 Jan 22;6(1):e1602. doi: 10.1038/cddis.2014.532.
18	In vivo effects of decitabine in myelodysplasia and acute myeloid leukemia: review of cytogenetic and molecular studies.Ann Hematol. 2005 Dec;84 Suppl 1:32-8. doi: 10.1007/s00277-005-0004-1.
19	Combining Type I Interferons and 5-Aza-2'-Deoxycitidine to Improve Anti-Tumor Response against Melanoma.J Invest Dermatol. 2017 Jan;137(1):159-169. doi: 10.1016/j.jid.2016.08.024. Epub 2016 Sep 10.
20	Suboptimal response rates to hypomethylating agent therapy in chronic myelomonocytic leukemia; a single institutional study of 121 patients.Am J Hematol. 2019 Jul;94(7):767-779. doi: 10.1002/ajh.25488. Epub 2019 May 3.
21	De novo single-nucleotide and copy number variation in discordant monozygotic twins reveals disease-related genes. Eur J Hum Genet. 2019 Jul;27(7):1121-1133. doi: 10.1038/s41431-019-0376-7. Epub 2019 Mar 18.
22	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
23	Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
24	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
25	Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
26	Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
27	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
28	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
29	Human arylacetamide deacetylase is responsible for deacetylation of rifamycins: rifampicin, rifabutin, and rifapentine. Biochem Pharmacol. 2011 Dec 1;82(11):1747-56.
30	Species differences in tissue distribution and enzyme activities of arylacetamide deacetylase in human, rat, and mouse. Drug Metab Dispos. 2012 Apr;40(4):671-9. doi: 10.1124/dmd.111.043067. Epub 2011 Dec 29.