Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKGI7BS)

• DOT Name: Serpin H1 (SERPINH1)
• Synonyms: 47 kDa heat shock protein; Arsenic-transactivated protein 3; AsTP3; Cell proliferation-inducing gene 14 protein; Collagen-binding protein; Colligin; Rheumatoid arthritis-related antigen RA-A47
• Gene Name: SERPINH1
• Related Disease:
  Osteogenesis imperfecta type 10
  Osteogenesis imperfecta type 3
• UniProt ID: SERPH_HUMAN
• Pfam ID: PF00079
• Sequence:
  MRSLLLLSAFCLLEAALAAEVKKPAAAAAPGTAEKLSPKAATLAERSAGLAFSLYQAMAK
  DQAVENILVSPVVVASSLGLVSLGGKATTASQAKAVLSAEQLRDEEVHAGLGELLRSLSN
  STARNVTWKLGSRLYGPSSVSFADDFVRSSKQHYNCEHSKINFRDKRSALQSINEWAAQT
  TDGKLPEVTKDVERTDGALLVNAMFFKPHWDEKFHHKMVDNRGFMVTRSYTVGVMMMHRT
  GLYNYYDDEKEKLQIVEMPLAHKLSSLIILMPHHVEPLERLEKLLTKEQLKIWMGKMQKK
  AVAISLPKGVVEVTHDLQKHLAGLGLTEAIDKNKADLSRMSGKKDLYLASVFHATAFELD
  TDGNPFDQDIYGREELRSPKLFYADHPFIFLVRDTQSGSLLFIGRLVRPKGDKMRDEL
• Function: Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen.
• Reactome Pathway: Collagen biosynthesis and modifying enzymes (R-HSA-1650814)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Osteogenesis imperfecta type 10	DISULIR7	Strong	Autosomal recessive	[1]
Osteogenesis imperfecta type 3	DISFJVSJ	Supportive	Autosomal dominant	[2]

22 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 Serpin H1 (SERPINH1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serpin H1 (SERPINH1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serpin H1 (SERPINH1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Serpin H1 (SERPINH1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Serpin H1 (SERPINH1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Serpin H1 (SERPINH1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Serpin H1 (SERPINH1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Serpin H1 (SERPINH1).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serpin H1 (SERPINH1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Serpin H1 (SERPINH1).	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Serpin H1 (SERPINH1).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Serpin H1 (SERPINH1).	[15]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Serpin H1 (SERPINH1).	[16]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Serpin H1 (SERPINH1).	[17]
Glucosamine	DM4ZLFD	Approved	Glucosamine increases the expression of Serpin H1 (SERPINH1).	[18]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Serpin H1 (SERPINH1).	[19]
NVP-AUY922	DMTYXQF	Phase 2	NVP-AUY922 decreases the expression of Serpin H1 (SERPINH1).	[20]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Serpin H1 (SERPINH1).	[22]
SB 203580	DMAET6F	Terminated	SB 203580 decreases the expression of Serpin H1 (SERPINH1).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Serpin H1 (SERPINH1).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Serpin H1 (SERPINH1).	[25]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Serpin H1 (SERPINH1).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Serpin H1 (SERPINH1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Serpin H1 (SERPINH1).	[21]

References

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• [5] 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.
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• [11] 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.
• [12] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [13] Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
• [14] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [15] 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.
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• [18] Glucosamine-induced endoplasmic reticulum dysfunction is associated with accelerated atherosclerosis in a hyperglycemic mouse model. Diabetes. 2006 Jan;55(1):93-101.
• [19] Resveratrol inhibits fibrogenesis and induces apoptosis in keloid fibroblasts. Wound Repair Regen. 2013 Jul-Aug;21(4):616-23. doi: 10.1111/wrr.12062.
• [20] Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry. Cells. 2019 Jul 31;8(8):806. doi: 10.3390/cells8080806.
• [21] 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.
• [22] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [23] Phenotypic switching of VEGF and collagen XVIII during hypoxia in head and neck squamous carcinoma cells. Oral Oncol. 2003 Dec;39(8):862-9. doi: 10.1016/s1368-8375(03)00110-6.
• [24] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [25] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [26] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.