Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQFN1TC)

• DOT Name: Cordon-bleu protein-like 1 (COBLL1)
• Gene Name: COBLL1
• Related Disease:
  Autism spectrum disorder
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Castration-resistant prostate carcinoma
  Prostate cancer
  Prostate carcinoma
  Tourette syndrome
  Non-insulin dependent diabetes
• UniProt ID: COBL1_HUMAN
• PDB ID: 2DAJ
• Pfam ID: PF09469
• Sequence:
  MDGRTPRPQDAPARRKPKAKAPLPPAETKYTDVSSAADSVESTAFIMEQKENMIDKDVEL
  SVVLPGDIIKSTTVHGSKPMMDLLIFLCAQYHLNPSSYTIDLLSAEQNHIKFKPNTPIGM
  LEVEKVILKPKMLDKKKPTPIIPEKTVRVVINFKKTQKTIVRVSPHASLQELAPIICSKC
  EFDPLHTLLLKDYQSQEPLDLTKSLNDLGLRELYAMDVNRESCQISQNLDIMKEKENKGF
  FSFFQRSKKKRDQTASAPATPLVNKHRPTFTRSNTISKPYISNTLPSDAPKKRRAPLPPM
  PASQSVPQDLAHIQERPASCIVKSMSVDETDKSPCEAGRVRAGSLQLSSMSAGNSSLRRT
  KRKAPSPPSKIPPHQSDENSRVTALQPVDGVPPDSASEANSPEELSSPAGISSDYSLEEI
  DEKEELSEVPKVEAENISPKSQDIPFVSTDIINTLKNDPDSALGNGSGEFSQNSMEEKQE
  TKSTDGQEPHSVVYDTSNGKKVVDSIRNLKSLGPNQENVVQNEIIVYPENTEDNMKNGVK
  KTEINVEGVAKNNNIDMEVERPSNSEAHETDTAISYKENHLAASSVPDQKLNQPSAEKTK
  DAAIQTTPSCNSFDGKHQDHNLSDSKVEECVQTSNNNISTQHSCLSSQDSVNTSREFRSQ
  GTLIIHSEDPLTVKDPICAHGNDDLLPPVDRIDKNSTASYLKNYPLYRQDYNPKPKPSNE
  ITREYIPKIGMTTYKIVPPKSLEISKDWQSETIEYKDDQDMHALGKKHTHENVKETAIQT
  EDSAISESPEEPLPNLKPKPNLRTEHQVPSSVSSPDDAMVSPLKPAPKMTRDTGTAPFAP
  NLEEINNILESKFKSRASNAQAKPSSFFLQMQKRVSGHYVTSAAAKSVHAAPNPAPKELT
  NKEAERDMLPSPEQTLSPLSKMPHSVPQPLVEKTDDDVIGQAPAEASPPPIAPKPVTIPA
  SQVSTQNLKTLKTFGAPRPYSSSGPSPFALAVVKRSQSFSKERTESPSASALVQPPANTE
  EGKTHSVNKFVDIPQLGVSDKENNSAHNEQNSQIPTPTDGPSFTVMRQSSLTFQSSDPEQ
  MRQSLLTAIRSGEAAAKLKRVTIPSNTISVNGRSRLSHSMSPDAQDGH

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[1]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Strong	Biomarker	[2]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Posttranslational Modification	[3]
Prostate cancer	DISF190Y	Strong	Altered Expression	[3]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[3]
Tourette syndrome	DISX9D54	Strong	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[4]

5 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 Cordon-bleu protein-like 1 (COBLL1).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Cordon-bleu protein-like 1 (COBLL1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cordon-bleu protein-like 1 (COBLL1).	[21]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Cordon-bleu protein-like 1 (COBLL1).	[20]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Cordon-bleu protein-like 1 (COBLL1).	[24]

16 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 Cordon-bleu protein-like 1 (COBLL1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cordon-bleu protein-like 1 (COBLL1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cordon-bleu protein-like 1 (COBLL1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cordon-bleu protein-like 1 (COBLL1).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cordon-bleu protein-like 1 (COBLL1).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cordon-bleu protein-like 1 (COBLL1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Cordon-bleu protein-like 1 (COBLL1).	[12]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cordon-bleu protein-like 1 (COBLL1).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Cordon-bleu protein-like 1 (COBLL1).	[14]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Cordon-bleu protein-like 1 (COBLL1).	[15]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Cordon-bleu protein-like 1 (COBLL1).	[16]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Cordon-bleu protein-like 1 (COBLL1).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cordon-bleu protein-like 1 (COBLL1).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cordon-bleu protein-like 1 (COBLL1).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cordon-bleu protein-like 1 (COBLL1).	[22]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Cordon-bleu protein-like 1 (COBLL1).	[23]

References

• [1] Heterozygous deletion of SCN2A and SCN3A in a patient with autism spectrum disorder and Tourette syndrome: a case report.BMC Psychiatry. 2018 Aug 2;18(1):248. doi: 10.1186/s12888-018-1822-8.
• [2] Cobll1 is linked to drug resistance and blastic transformation in chronic myeloid leukemia.Leukemia. 2017 Jul;31(7):1532-1539. doi: 10.1038/leu.2017.72. Epub 2017 Feb 24.
• [3] COBLL1 modulates cell morphology and facilitates androgen receptor genomic binding in advanced prostate cancer.Proc Natl Acad Sci U S A. 2018 May 8;115(19):4975-4980. doi: 10.1073/pnas.1721957115. Epub 2018 Apr 23.
• [4] Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population.Nat Genet. 2019 Mar;51(3):379-386. doi: 10.1038/s41588-018-0332-4. Epub 2019 Feb 4.
• [5] 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.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] 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.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] 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.
• [12] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [13] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [14] 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.
• [15] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [16] 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.
• [17] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [18] 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.
• [19] 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.
• [20] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [21] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [22] 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.
• [23] 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.
• [24] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.