Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMMV6WZ)

• DOT Name: Lysine-rich coiled-coil protein 1 (KRCC1)
• Synonyms: Cryptogenic hepatitis-binding protein 2
• Gene Name: KRCC1
• UniProt ID: KRCC1_HUMAN
• Sequence:
  MKHSKKTYDSFQDELEDYIKVQKARGLEPKTCFRKMKGDYLETCGYKGEVNSRPTYRMFD
  QRLPSETIQTYPRSCNIPQTVENRLPQWLPAHDSRLRLDSLSYCQFTRDCFSEKPVPLNF
  NQQEYICGSHGVEHRVYKHFSSDNSTSTHQASHKQIHQKRKRHPEEGREKSEEERSKHKR
  KKSCEEIDLDKHKSIQRKKTEVEIETVHVSTEKLKNRKEKKSRDVVSKKEERKRTKKKKE
  QGQERTEEEMLWDQSILGF

Molecular Interaction Atlas (MIA) of This DOT

20 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 Lysine-rich coiled-coil protein 1 (KRCC1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[8]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[16]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[17]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[18]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Lysine-rich coiled-coil protein 1 (KRCC1).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [8] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [9] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] 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.
• [13] Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S. Toxicol In Vitro. 2015 Aug;29(5):1060-9.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [18] 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.