Details of Drug Off-Target (DOT)

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

• DOT Name: Cadherin-11 (CDH11)
• Synonyms: OSF-4; Osteoblast cadherin; OB-cadherin
• Gene Name: CDH11
• Related Disease:
  Elsahy-Waters syndrome
  Teebi hypertelorism syndrome 2
• UniProt ID: CAD11_HUMAN
• Pfam ID: PF01049 ; PF00028
• Sequence:
  MKENYCLQAALVCLGMLCHSHAFAPERRGHLRPSFHGHHEKGKEGQVLQRSKRGWVWNQF
  FVIEEYTGPDPVLVGRLHSDIDSGDGNIKYILSGEGAGTIFVIDDKSGNIHATKTLDREE
  RAQYTLMAQAVDRDTNRPLEPPSEFIVKVQDINDNPPEFLHETYHANVPERSNVGTSVIQ
  VTASDADDPTYGNSAKLVYSILEGQPYFSVEAQTGIIRTALPNMDREAKEEYHVVIQAKD
  MGGHMGGLSGTTKVTITLTDVNDNPPKFPQSVYQMSVSEAAVPGEEVGRVKAKDPDIGEN
  GLVTYNIVDGDGMESFEITTDYETQEGVIKLKKPVDFETKRAYSLKVEAANVHIDPKFIS
  NGPFKDTVTVKISVEDADEPPMFLAPSYIHEVQENAAAGTVVGRVHAKDPDAANSPIRYS
  IDRHTDLDRFFTINPEDGFIKTTKPLDREETAWLNITVFAAEIHNRHQEAKVPVAIRVLD
  VNDNAPKFAAPYEGFICESDQTKPLSNQPIVTISADDKDDTANGPRFIFSLPPEIIHNPN
  FTVRDNRDNTAGVYARRGGFSRQKQDLYLLPIVISDGGIPPMSSTNTLTIKVCGCDVNGA
  LLSCNAEAYILNAGLSTGALIAILACIVILLVIVVLFVTLRRQKKEPLIVFEEEDVRENI
  ITYDDEGGGEEDTEAFDIATLQNPDGINGFIPRKDIKPEYQYMPRPGLRPAPNSVDVDDF
  INTRIQEADNDPTAPPYDSIQIYGYEGRGSVAGSLSSLESATTDSDLDYDYLQNWGPRFK
  KLADLYGSKDTFDDDS
• Function: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. Required for proper focal adhesion assembly. Involved in the regulation of cell migration.
• Tissue Specificity: Expressed mainly in brain but also found in other tissues. Expressed in neuroblasts. In the embryo from 67 to 72 days of gestation, detected at high levels in facial mesenchyme including the central palatal mesenchyme, dental mesenchyme, the eye and optic muscle, and the tongue (at protein level) .
• Reactome Pathway:
  CDH11 homotypic and heterotypic interactions (R-HSA-9833576)
  Adherens junctions interactions (R-HSA-418990)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Elsahy-Waters syndrome	DISFWWGF	Definitive	Autosomal recessive	[1]
Teebi hypertelorism syndrome 2	DISBU3V7	Strong	Autosomal dominant	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Dexamethasone	DMMWZET	Approved	Cadherin-11 (CDH11) increases the Bone disorder ADR of Dexamethasone.	[22]

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 Cadherin-11 (CDH11).	[3]

22 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 Cadherin-11 (CDH11).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cadherin-11 (CDH11).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cadherin-11 (CDH11).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cadherin-11 (CDH11).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Cadherin-11 (CDH11).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cadherin-11 (CDH11).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Cadherin-11 (CDH11).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cadherin-11 (CDH11).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Cadherin-11 (CDH11).	[11]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Cadherin-11 (CDH11).	[12]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Cadherin-11 (CDH11).	[13]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Cadherin-11 (CDH11).	[14]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Cadherin-11 (CDH11).	[15]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Cadherin-11 (CDH11).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Cadherin-11 (CDH11).	[17]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Cadherin-11 (CDH11).	[11]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Cadherin-11 (CDH11).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Cadherin-11 (CDH11).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cadherin-11 (CDH11).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cadherin-11 (CDH11).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cadherin-11 (CDH11).	[11]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Cadherin-11 (CDH11).	[4]

References

• [1] Detailed clinical and radiological features of the first patient with Elsahy-Waters syndrome in East Asia. Am J Med Genet A. 2021 Dec;185(12):3909-3915. doi: 10.1002/ajmg.a.62423. Epub 2021 Jul 19.
• [2] Pathogenic variants in CDH11 impair cell adhesion and cause Teebi hypertelorism syndrome. Hum Genet. 2021 Jul;140(7):1061-1076. doi: 10.1007/s00439-021-02274-3. Epub 2021 Apr 3.
• [3] 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.
• [4] Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals. Int J Mol Sci. 2021 Oct 12;22(20):11005. doi: 10.3390/ijms222011005.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] 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.
• [7] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [8] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [11] Extended treatment with physiologic concentrations of dietary phytochemicals results in altered gene expression, reduced growth, and apoptosis of cancer cells. Mol Cancer Ther. 2007 Nov;6(11):3071-9. doi: 10.1158/1535-7163.MCT-07-0117.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] 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.
• [14] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [15] Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009 Aug 21;138(4):645-659. doi: 10.1016/j.cell.2009.06.034. Epub 2009 Aug 13.
• [16] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [17] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [18] Regulation of aryl hydrocarbon receptor function by selective estrogen receptor modulators. Mol Endocrinol. 2010 Jan;24(1):33-46.
• [19] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [20] 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.
• [21] 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.
• [22] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.