Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT83P1E0)

DOT Name Forkhead box protein C2 (FOXC2)
Synonyms Forkhead-related protein FKHL14; Mesenchyme fork head protein 1; MFH-1 protein; Transcription factor FKH-14
Gene Name FOXC2
Related Disease
Lymphedema-distichiasis syndrome ( )
UniProt ID
FOXC2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1D5V; 6AKO; 6AKP; 6LBM; 6O3T
Pfam ID
PF00250
Sequence
MQARYSVSDPNALGVVPYLSEQNYYRAAGSYGGMASPMGVYSGHPEQYSAGMGRSYAPYH
HHQPAAPKDLVKPPYSYIALITMAIQNAPEKKITLNGIYQFIMDRFPFYRENKQGWQNSI
RHNLSLNECFVKVPRDDKKPGKGSYWTLDPDSYNMFENGSFLRRRRRFKKKDVSKEKEER
AHLKEPPPAASKGAPATPHLADAPKEAEKKVVIKSEAASPALPVITKVETLSPESALQGS
PRSAASTPAGSPDGSLPEHHAAAPNGLPGFSVENIMTLRTSPPGGELSPGAGRAGLVVPP
LALPYAAAPPAAYGQPCAQGLEAGAAGGYQCSMRAMSLYTGAERPAHMCVPPALDEALSD
HPSGPTSPLSALNLAAGQEGALAATGHHHQHHGHHHPQAPPPPPAPQPQPTPQPGAAAAQ
AASWYLNHSGDLNHLPGHTFAAQQQTFPNVREMFNSHRLGIENSTLGESQVSGNASCQLP
YRSTPPLYRHAAPYSYDCTKY
Function Transcriptional activator.
Reactome Pathway
Formation of intermediate mesoderm (R-HSA-9761174 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Lymphedema-distichiasis syndrome DISUJCP4 Definitive Autosomal dominant [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 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 Forkhead box protein C2 (FOXC2). [2]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Forkhead box protein C2 (FOXC2). [2]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Forkhead box protein C2 (FOXC2). [3]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Forkhead box protein C2 (FOXC2). [4]
Cannabidiol DM0659E Approved Cannabidiol increases the expression of Forkhead box protein C2 (FOXC2). [5]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Forkhead box protein C2 (FOXC2). [2]
Thalidomide DM70BU5 Approved Thalidomide decreases the expression of Forkhead box protein C2 (FOXC2). [2]
Phenytoin DMNOKBV Approved Phenytoin decreases the expression of Forkhead box protein C2 (FOXC2). [2]
Nilotinib DM7HXWT Approved Nilotinib decreases the expression of Forkhead box protein C2 (FOXC2). [2]
Abacavir DMMN36E Approved Abacavir decreases the expression of Forkhead box protein C2 (FOXC2). [2]
Polyethylene glycol DM4I1JP Approved Polyethylene glycol decreases the expression of Forkhead box protein C2 (FOXC2). [2]
Dabigatran DMDI6R4 Approved Dabigatran decreases the expression of Forkhead box protein C2 (FOXC2). [2]
Belinostat DM6OC53 Phase 2 Belinostat increases the expression of Forkhead box protein C2 (FOXC2). [4]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Forkhead box protein C2 (FOXC2). [4]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Forkhead box protein C2 (FOXC2). [8]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Forkhead box protein C2 (FOXC2). [9]
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⏷ Show the Full List of 16 Drug(s)
2 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 decreases the methylation of Forkhead box protein C2 (FOXC2). [6]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Forkhead box protein C2 (FOXC2). [7]
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References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
3 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.
4 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.
5 Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
6 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.
7 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
8 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
9 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.