Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3A21CM)

• DOT Name: SHC SH2 domain-binding protein 1 (SHCBP1)
• Gene Name: SHCBP1
• UniProt ID: SHCBP_HUMAN
• Pfam ID: PF13229
• Sequence:
  MADGSLTGGGLEAAAMAPERMGWAVEQELASLEKGLFQDEDSCSDCSYRDKPGSSLQSFM
  PEGKTFFPEIFQTNQLLFYERFRAYQDYILADCKASEVQEFTAEFLEKVLEPSGWRAVWH
  TNVFKVLVEITDVDFAALKAVVRLAEPYLCDSQVSTFTMECMKELLDLKEHRLPLQELWV
  VFDDSGVFDQTALAIEHVRFFYQNIWRSWDEEEEDEYDYFVRCVEPRLRLHYDILEDRVP
  SGLIVDYHNLLSQCEESYRKFLNLRSSLSNCNSDSEQENISMVEGLKLYSEMEQLKQKLK
  LIENPLLRYVFGYQKNSNIQAKGVRSSGQKITHVVSSTMMAGLLRSLLTDRLCQEPGEEE
  REIQFHSDPLSAINACFEGDTVIVCPGHYVVHGTFSIADSIELEGYGLPDDIVIEKRGKG
  DTFVDCTGADIKISGIKFVQHDAVEGILIVHRGKTTLENCVLQCETTGVTVRTSAEFLMK
  NSDLYGAKGAGIEIYPGSQCTLSDNGIHHCKEGILIKDFLDEHYDIPKISMVNNIIHNNE
  GYGVVLVKPTIFSDLQENAEDGTEENKALKIQTSGEPDVAERVDLEELIECATGKMELCA
  RTDPSEQVEGNCEIVNELIAASTQKGQIKKKRLSELGITQADDNLMSQEMFVGIVGNQFK
  WNGKGSFGTFLF
• Function: May play a role in signaling pathways governing cellular proliferation, cell growth and differentiation. May be a component of a novel signaling pathway downstream of Shc. Acts as a positive regulator of FGF signaling in neural progenitor cells.

Molecular Interaction Atlas (MIA) of This DOT

27 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 SHC SH2 domain-binding protein 1 (SHCBP1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[11]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[12]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[13]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[14]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[15]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[16]
Methamphetamine	DMPM4SK	Approved	Methamphetamine decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[17]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[18]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[22]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[24]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[25]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[26]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of SHC SH2 domain-binding protein 1 (SHCBP1).	[27]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of SHC SH2 domain-binding protein 1 (SHCBP1).	[23]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Global gene expression profiles induced by phytoestrogens in human breast cancer cells. Endocr Relat Cancer. 2008 Mar;15(1):161-73.
• [8] 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.
• [9] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [10] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [11] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [12] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [13] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [14] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [15] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [16] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [17] Methamphetamine alters the normal progression by inducing cell cycle arrest in astrocytes. PLoS One. 2014 Oct 7;9(10):e109603.
• [18] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [19] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [20] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [25] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [26] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [27] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.