Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM0V5AO)

• DOT Name: Integrin alpha-10 (ITGA10)
• Gene Name: ITGA10
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Advanced cancer
  Melanoma
  Neoplasm
• UniProt ID: ITA10_HUMAN
• Pfam ID: PF01839 ; PF08441 ; PF20805 ; PF00092
• Sequence:
  MELPFVTHLFLPLVFLTGLCSPFNLDEHHPRLFPGPPEAEFGYSVLQHVGGGQRWMLVGA
  PWDGPSGDRRGDVYRCPVGGAHNAPCAKGHLGDYQLGNSSHPAVNMHLGMSLLETDGDGG
  FMACAPLWSRACGSSVFSSGICARVDASFQPQGSLAPTAQRCPTYMDVVIVLDGSNSIYP
  WSEVQTFLRRLVGKLFIDPEQIQVGLVQYGESPVHEWSLGDFRTKEEVVRAAKNLSRREG
  RETKTAQAIMVACTEGFSQSHGGRPEAARLLVVVTDGESHDGEELPAALKACEAGRVTRY
  GIAVLGHYLRRQRDPSSFLREIRTIASDPDERFFFNVTDEAALTDIVDALGDRIFGLEGS
  HAENESSFGLEMSQIGFSTHRLKDGILFGMVGAYDWGGSVLWLEGGHRLFPPRMALEDEF
  PPALQNHAAYLGYSVSSMLLRGGRRLFLSGAPRFRHRGKVIAFQLKKDGAVRVAQSLQGE
  QIGSYFGSELCPLDTDRDGTTDVLLVAAPMFLGPQNKETGRVYVYLVGQQSLLTLQGTLQ
  PEPPQDARFGFAMGALPDLNQDGFADVAVGAPLEDGHQGALYLYHGTQSGVRPHPAQRIA
  AASMPHALSYFGRSVDGRLDLDGDDLVDVAVGAQGAAILLSSRPIVHLTPSLEVTPQAIS
  VVQRDCRRRGQEAVCLTAALCFQVTSRTPGRWDHQFYMRFTASLDEWTAGARAAFDGSGQ
  RLSPRRLRLSVGNVTCEQLHFHVLDTSDYLRPVALTVTFALDNTTKPGPVLNEGSPTSIQ
  KLVPFSKDCGPDNECVTDLVLQVNMDIRGSRKAPFVVRGGRRKVLVSTTLENRKENAYNT
  SLSLIFSRNLHLASLTPQRESPIKVECAAPSAHARLCSVGHPVFQTGAKVTFLLEFEFSC
  SSLLSQVFVKLTASSDSLERNGTLQDNTAQTSAYIQYEPHLLFSSESTLHRYEVHPYGTL
  PVGPGPEFKTTLRVQNLGCYVVSGLIISALLPAVAHGGNYFLSLSQVITNNASCIVQNLT
  EPPGPPVHPEELQHTNRLNGSNTQCQVVRCHLGQLAKGTEVSVGLLRLVHNEFFRRAKFK
  SLTVVSTFELGTEEGSVLQLTEASRWSESLLEVVQTRPILISLWILIGSVLGGLLLLALL
  VFCLWKLGFFAHKKIPEEEKREEKLEQ
• Function: Integrin alpha-10/beta-1 is a receptor for collagen.
• Tissue Specificity: Widely expressed with highest expression in muscle and heart. Found in articular cartilage.
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Regulation of actin cytoskeleton (hsa04810)
  Cytoskeleton in muscle cells (hsa04820)
  Human papillomavirus infection (hsa05165)
  Hypertrophic cardiomyopathy (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway:
  CHL1 interactions (R-HSA-447041)
  Platelet Adhesion to exposed collagen (R-HSA-75892)
  Integrin cell surface interactions (R-HSA-216083)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[2]
Melanoma	DIS1RRCY	Limited	Genetic Variation	[3]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]

10 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 Integrin alpha-10 (ITGA10).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Integrin alpha-10 (ITGA10).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Integrin alpha-10 (ITGA10).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Integrin alpha-10 (ITGA10).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Integrin alpha-10 (ITGA10).	[8]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Integrin alpha-10 (ITGA10).	[9]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of Integrin alpha-10 (ITGA10).	[10]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Integrin alpha-10 (ITGA10).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Integrin alpha-10 (ITGA10).	[11]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Integrin alpha-10 (ITGA10).	[11]

References

• [1] Integrin 10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival.Cancers (Basel). 2019 Apr 25;11(4):587. doi: 10.3390/cancers11040587.
• [2] Integrin-10 Dependency Identifies RAC and RICTOR as Therapeutic Targets in High-Grade Myxofibrosarcoma.Cancer Discov. 2016 Oct;6(10):1148-1165. doi: 10.1158/2159-8290.CD-15-1481. Epub 2016 Aug 30.
• [3] Integrin genes and susceptibility to human melanoma.Mutagenesis. 2012 May;27(3):367-73. doi: 10.1093/mutage/ger090. Epub 2011 Dec 20.
• [4] 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.
• [5] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [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] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [10] Ultradian cortisol pulsatility encodes a distinct, biologically important signal. PLoS One. 2011 Jan 18;6(1):e15766.
• [11] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.