Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTIZO7B)

• DOT Name: T-complex protein 11-like protein 2 (TCP11L2)
• Gene Name: TCP11L2
• Related Disease: Schizophrenia
• UniProt ID: T11L2_HUMAN
• Pfam ID: PF05794
• Sequence:
  MPFNGEKQCVGEDQPSDSDSSRFSESMASLSDYECSRQSFASDSSSKSSSPASTSPPRVV
  TFDEVMATARNLSNLTLAHEIAVNENFQLKQEALPEKSLAGRVKHIVHQAFWDVLDSELN
  ADPPEFEHAIKLFEEIREILLSFLTPGGNRLRNQICEVLDTDLIRQQAEHSAVDIQGLAN
  YVISTMGKLCAPVRDNDIRELKATGNIVEVLRQIFHVLDLMQMDMANFTIMSLRPHLQRQ
  LVEYERTKFQEILEETPSALDQTTEWIKESVNEELFSLSESALTPGAENTSKPSLSPTLV
  LNNSYLKLLQWDYQKKELPETLMTDGARLQELTEKLNQLKIIACLSLITNNMVGAITGGL
  PELASRLTRISAVLLEGMNKETFNLKEVLNSIGIQTCVEVNKTLMERGLPTLNAEIQANL
  IGQFSSIEEEDNPIWSLIDKRIKLYMRRLLCLPSPQKCMPPMPGGLAVIQQELEALGSQY
  ANIVNLNKQVYGPFYANILRKLLFNEEAMGKVDASPPTN
• Function: Promotes the migration of muscle-derived satellite cells (MDSCs) during differentiation throught interaction with FMNL2 and therefore may participate in microfilament assembly.

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	No Known	Unknown	[1]

19 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of T-complex protein 11-like protein 2 (TCP11L2).	[8]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[9]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[10]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[12]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[13]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[16]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[20]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of T-complex protein 11-like protein 2 (TCP11L2).	[21]

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 T-complex protein 11-like protein 2 (TCP11L2).	[15]

References

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• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [8] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [10] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [11] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Application of the adverse outcome pathway concept for investigating developmental neurotoxicity potential of Chinese herbal medicines by using human neural progenitor cells in vitro. Cell Biol Toxicol. 2023 Feb;39(1):319-343. doi: 10.1007/s10565-022-09730-4. Epub 2022 Jun 15.
• [14] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [15] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [16] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [17] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [18] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [19] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [21] Effects of nickel treatment on H3K4 trimethylation and gene expression. PLoS One. 2011 Mar 24;6(3):e17728. doi: 10.1371/journal.pone.0017728.