Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7NQWJK)

• DOT Name: Activity-dependent neuroprotector homeobox protein 2 (ADNP2)
• Synonyms: ADNP homeobox protein 2; Zinc finger protein 508
• Gene Name: ADNP2
• Related Disease: Schizophrenia
• UniProt ID: ADNP2_HUMAN
• Pfam ID: PF19627
• Sequence:
  MFQIPVENLDNIRKVRKKVKGILVDIGLDSCKELLKDLKGFDPGEKYFHNTSWGDVSLWE
  PSGKKVRYRTKPYCCGLCKYSTKVLTSFKNHLHRYHEDEIDQELVIPCPNCVFASQPKVV
  GRHFRMFHAPVRKVQNYTVNILGETKSSRSDVISFTCLKCNFSNTLYYSMKKHVLVAHFH
  YLINSYFGLRTEEMGEQPKTNDTVSIEKIPPPDKYYCKKCNANASSQDALMYHILTSDIH
  RDLENKLRSVISEHIKRTGLLKQTHIAPKPAAHLAAPANGSAPSAPAQPPCFHLALPQNS
  PSPAAGQPVTVAQGAPGSLTHSPPAAGQSHMTLVSSPLPVGQNSLTLQPPAPQPVFLSHG
  VPLHQSVNPPVLPLSQPVGPVNKSVGTSVLPINQTVRPGVLPLTQPVGPINRPVGPGVLP
  VSPSVTPGVLQAVSPGVLSVSRAVPSGVLPAGQMTPAGQMTPAGVIPGQTATSGVLPTGQ
  MVQSGVLPVGQTAPSRVLPPGQTAPLRVISAGQVVPSGLLSPNQTVSSSAVVPVNQGVNS
  GVLQLSQPVVSGVLPVGQPVRPGVLQLNQTVGTNILPVNQPVRPGASQNTTFLTSGSILR
  QLIPTGKQVNGIPTYTLAPVSVTLPVPPGGLATVAPPQMPIQLLPSGAAAPMAGSMPGMP
  SPPVLVNAAQSVFVQASSSAADTNQVLKQAKQWKTCPVCNELFPSNVYQVHMEVAHKHSE
  SKSGEKLEPEKLAACAPFLKWMREKTVRCLSCKCLVSEEELIHHLLMHGLGCLFCPCTFH
  DIKGLSEHSRNRHLGKKKLPMDYSNRGFQLDVDANGNLLFPHLDFITILPKEKLGEREVY
  LAILAGIHSKSLVPVYVKVRPQAEGTPGSTGKRVSTCPFCFGPFVTTEAYELHLKERHHI
  MPTVHTVLKSPAFKCIHCCGVYTGNMTLAAIAVHLVRCRSAPKDSSSDLQAQPGFIHNSE
  LLLVSGEVMHDSSFSVKRKLPDGHLGAEDQRHGEEQPPILNADAAPGPEKVTSVVPFKRQ
  RNESRTEGPIVKDEALQILALDPKKYEGRSYEEKKQFLKDYFHKKPYPSKKEIELLSSLF
  WVWKIDVASFFGKRRYICMKAIKNHKPSVLLGFDMSELKNVKHRLNFEYEP
• Function: May be involved in transcriptional regulation. May play a role in neuronal function; perhaps involved in protection of brain tissues from oxidative stress. May be involved in erythroid differentiation.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	moderate	Biomarker	[1]

9 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 Activity-dependent neuroprotector homeobox protein 2 (ADNP2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Activity-dependent neuroprotector homeobox protein 2 (ADNP2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Activity-dependent neuroprotector homeobox protein 2 (ADNP2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Activity-dependent neuroprotector homeobox protein 2 (ADNP2).	[5]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Activity-dependent neuroprotector homeobox protein 2 (ADNP2).	[6]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Activity-dependent neuroprotector homeobox protein 2 (ADNP2).	[4]
Lithium	DMZ3OU6	Phase 2	Lithium increases the expression of Activity-dependent neuroprotector homeobox protein 2 (ADNP2).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Activity-dependent neuroprotector homeobox protein 2 (ADNP2).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Activity-dependent neuroprotector homeobox protein 2 (ADNP2).	[10]

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 Activity-dependent neuroprotector homeobox protein 2 (ADNP2).	[7]

References

• [1] Autophagy has a key role in the pathophysiology of schizophrenia.Mol Psychiatry. 2015 Feb;20(1):126-32. doi: 10.1038/mp.2013.174. Epub 2013 Dec 24.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [7] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [8] Effect of mood stabilizers on gene expression in lymphoblastoid cells. J Neural Transm (Vienna). 2010 Feb;117(2):155-64.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.