Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOXC51H)

• DOT Name: Metalloproteinase inhibitor 1 (TIMP1)
• Synonyms: Erythroid-potentiating activity; EPA; Fibroblast collagenase inhibitor; Collagenase inhibitor; Tissue inhibitor of metalloproteinases 1; TIMP-1
• Gene Name: TIMP1
• Related Disease:
  Chronic obstructive pulmonary disease
  Dilated cardiomyopathy 1A
  Inflammatory bowel disease
  Lung cancer
  Lung carcinoma
  Melanoma
  Squamous cell carcinoma
  Type-1 diabetes
  Vascular disease
  Alcoholic cirrhosis of liver
  Alzheimer disease
  Astrocytoma
  Atherosclerosis
  Autoimmune disease
  Breast neoplasm
  Cardiac disease
  Cholangitis
  Cholestasis
  Colon cancer
  Colorectal neoplasm
  Glioblastoma multiforme
  Hepatocellular carcinoma
  High blood pressure
  IgA nephropathy
  Keratoconus
  Metastatic malignant neoplasm
  Multiple sclerosis
  Myocardial infarction
  Osteoarthritis
  Pancreatic cancer
  Pulmonary fibrosis
  Rheumatoid arthritis
  Stroke
  Systemic sclerosis
  Thyroid gland papillary carcinoma
  Thyroid tumor
  Wilson disease
  Calcinosis
  Colon carcinoma
  Familial tumoral calcinosis
  Gastric ulcer
  Heart valve disorder
  Adult respiratory distress syndrome
  Carcinoma
  Varicose veins
• UniProt ID: TIMP1_HUMAN
• PDB ID: 1D2B; 1OO9; 1UEA; 2J0T; 3MA2; 3V96; 6MAV; 6N9D; 7S7L; 7S7M
• Pfam ID: PF00965
• Sequence:
  MAPFEPLASGILLLLWLIAPSRACTCVPPHPQTAFCNSDLVIRAKFVGTPEVNQTTLYQR
  YEIKMTKMYKGFQALGDAADIRFVYTPAMESVCGYFHRSHNRSEEFLIAGKLQDGLLHIT
  TCSFVAPWNSLSLAQRRGFTKTYTVGCEECTVFPCLSIPCKLQSGTHCLWTDQLLQGSEK
  GFQSRHLACLPREPGLCTWQSLRSQIA
• Function: Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16. Does not act on MMP14. Also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signaling cascades via CD63 and ITGB1. Plays a role in integrin signaling. Mediates erythropoiesis in vitro; but, unlike IL3, it is species-specific, stimulating the growth and differentiation of only human and murine erythroid progenitors.
• Tissue Specificity: Detected in rheumatoid synovial fluid (at protein level).
• KEGG Pathway: HIF-1 sig.ling pathway (hsa04066)
• Reactome Pathway:
  Activation of Matrix Metalloproteinases (R-HSA-1592389)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Interleukin-10 signaling (R-HSA-6783783)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic obstructive pulmonary disease	DISQCIRF	Definitive	Biomarker	[1]
Dilated cardiomyopathy 1A	DIS0RK9Z	Definitive	Biomarker	[2]
Inflammatory bowel disease	DISGN23E	Definitive	Altered Expression	[3]
Lung cancer	DISCM4YA	Definitive	Biomarker	[4]
Lung carcinoma	DISTR26C	Definitive	Biomarker	[4]
Melanoma	DIS1RRCY	Definitive	Altered Expression	[5]
Squamous cell carcinoma	DISQVIFL	Definitive	Altered Expression	[6]
Type-1 diabetes	DIS7HLUB	Definitive	Biomarker	[7]
Vascular disease	DISVS67S	Definitive	Biomarker	[8]
Alcoholic cirrhosis of liver	DISQ1WRT	Strong	Biomarker	[9]
Alzheimer disease	DISF8S70	Strong	Biomarker	[10]
Astrocytoma	DISL3V18	Strong	Biomarker	[11]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[12]
Autoimmune disease	DISORMTM	Strong	Biomarker	[13]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[14]
Cardiac disease	DISVO1I5	Strong	Biomarker	[15]
Cholangitis	DIS9U3YN	Strong	Biomarker	[16]
Cholestasis	DISDJJWE	Strong	Biomarker	[17]
Colon cancer	DISVC52G	Strong	Altered Expression	[18]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[19]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[20]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[21]
High blood pressure	DISY2OHH	Strong	Biomarker	[22]
IgA nephropathy	DISZ8MTK	Strong	Biomarker	[23]
Keratoconus	DISOONXH	Strong	Altered Expression	[24]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[25]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[26]
Myocardial infarction	DIS655KI	Strong	Biomarker	[27]
Osteoarthritis	DIS05URM	Strong	Biomarker	[28]
Pancreatic cancer	DISJC981	Strong	Biomarker	[29]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[30]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[31]
Stroke	DISX6UHX	Strong	Altered Expression	[32]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[33]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Biomarker	[25]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[34]
Wilson disease	DISVS9H7	Strong	Biomarker	[35]
Calcinosis	DISQP4OR	moderate	Biomarker	[36]
Colon carcinoma	DISJYKUO	moderate	Altered Expression	[18]
Familial tumoral calcinosis	DISYJZKG	moderate	Biomarker	[36]
Gastric ulcer	DISBBGVO	moderate	Biomarker	[37]
Heart valve disorder	DIS84O7T	moderate	Biomarker	[36]
Adult respiratory distress syndrome	DISIJV47	Limited	Biomarker	[38]
Carcinoma	DISH9F1N	Limited	Altered Expression	[39]
Varicose veins	DISIMBN2	Limited	Biomarker	[40]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Pentoxifylline	DMU3DNC	Approved	Metalloproteinase inhibitor 1 (TIMP1) increases the Iron and trace metal metabolism disorders ADR of Pentoxifylline.	[109]

2 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 Metalloproteinase inhibitor 1 (TIMP1).	[41]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Metalloproteinase inhibitor 1 (TIMP1).	[86]

76 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 Metalloproteinase inhibitor 1 (TIMP1).	[42]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[43]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[44]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Metalloproteinase inhibitor 1 (TIMP1).	[45]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[46]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[47]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[48]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[49]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[50]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[51]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[52]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[53]
Marinol	DM70IK5	Approved	Marinol increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[54]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[55]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[56]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[57]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[58]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[59]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[60]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[61]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[62]
Nicotine	DMWX5CO	Approved	Nicotine affects the expression of Metalloproteinase inhibitor 1 (TIMP1).	[63]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[64]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[65]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[66]
Sulindac	DM2QHZU	Approved	Sulindac affects the expression of Metalloproteinase inhibitor 1 (TIMP1).	[67]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[68]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[42]
Vitamin C	DMXJ7O8	Approved	Vitamin C increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[69]
Dinoprostone	DMTYOPD	Approved	Dinoprostone increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[54]
Ampicillin	DMHWE7P	Approved	Ampicillin decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[70]
Isoproterenol	DMK7MEY	Approved	Isoproterenol decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[71]
Artesunate	DMR27C8	Approved	Artesunate increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[72]
Flurbiprofen	DMGN4BY	Approved	Flurbiprofen increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[73]
Lamivudine	DMI347A	Approved	Lamivudine decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[74]
Meclizine	DMS7T13	Approved	Meclizine affects the expression of Metalloproteinase inhibitor 1 (TIMP1).	[67]
Methazolamide	DM7J2TA	Approved	Methazolamide affects the expression of Metalloproteinase inhibitor 1 (TIMP1).	[67]
Megestrol	DMDH9KX	Approved	Megestrol affects the expression of Metalloproteinase inhibitor 1 (TIMP1).	[67]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[75]
Beclomethasone dipropionate	DM5NW1E	Phase 4	Beclomethasone dipropionate increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[76]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[77]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[43]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[78]
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[72]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[79]
Thymoquinone	DMVDTR2	Phase 2/3	Thymoquinone increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[80]
Verapamil	DMA7PEW	Phase 2/3 Trial	Verapamil affects the expression of Metalloproteinase inhibitor 1 (TIMP1).	[67]
Contigoside B	DMX9V8K	Phase 2/3	Contigoside B increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[81]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[82]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[83]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[84]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[85]
Arecoline	DMFJZK3	Phase 1	Arecoline increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[87]
PGF2alpha	DM4XAU7	Clinical trial	PGF2alpha decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[64]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[89]
Piperazinyl methyl quinazolinone derivative 2	DM913KS	Patented	Piperazinyl methyl quinazolinone derivative 2 decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[90]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[91]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[58]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[92]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[93]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[94]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[95]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate affects the activity of Metalloproteinase inhibitor 1 (TIMP1).	[96]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[97]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[99]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[100]
Oleic acid	DM54O1Z	Investigative	Oleic acid increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[101]
PD98059	DMZC90M	Investigative	PD98059 decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[102]
NAPQI	DM8F5LR	Investigative	NAPQI increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[103]
I-BET151	DMYRUH2	Investigative	I-BET151 decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[104]
PFI-1	DMVFK3J	Investigative	PFI-1 decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[104]
Anandamide	DMCKH3P	Investigative	Anandamide increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[54]
ROLIPRAM	DMJ03UM	Investigative	ROLIPRAM decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[105]
LY2109761	DMAWTG3	Investigative	LY2109761 increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[106]
RGD	DMFASRB	Investigative	RGD decreases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[107]
trichloroethanol	DMNALMF	Investigative	trichloroethanol increases the expression of Metalloproteinase inhibitor 1 (TIMP1).	[108]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Metastat	DMTQ4PN	Phase 1	Metastat decreases the secretion of Metalloproteinase inhibitor 1 (TIMP1).	[88]
D-glucose	DMMG2TO	Investigative	D-glucose increases the secretion of Metalloproteinase inhibitor 1 (TIMP1).	[98]

References

• [1] Relationship Between Circulating Serpina3g, Matrix Metalloproteinase-9, and Tissue Inhibitor of Metalloproteinase-1 and -2 with Chronic Obstructive Pulmonary Disease Severity.Biomolecules. 2019 Feb 13;9(2):62. doi: 10.3390/biom9020062.
• [2] Tissue Inhibitor of Matrix Metalloproteinase-1 Promotes Myocardial Fibrosis by Mediating CD63-Integrin 1 Interaction.Hypertension. 2017 Jun;69(6):1092-1103. doi: 10.1161/HYPERTENSIONAHA.117.09045. Epub 2017 Apr 3.
• [3] TIMP1 mRNA in tumor-educated platelets is diagnostic biomarker for colorectal cancer.Aging (Albany NY). 2019 Oct 22;11(20):8998-9012. doi: 10.18632/aging.102366. Epub 2019 Oct 22.
• [4] VAMP8, a vesicle-SNARE required for RAB37-mediated exocytosis, possesses a tumor metastasis suppressor function.Cancer Lett. 2018 Nov 28;437:79-88. doi: 10.1016/j.canlet.2018.08.023. Epub 2018 Aug 27.
• [5] Effects of nano-encapsulated curcumin-chrysin on telomerase, MMPs and TIMPs gene expression in mouse B16F10 melanoma tumour model.Artif Cells Nanomed Biotechnol. 2018;46(sup2):75-86. doi: 10.1080/21691401.2018.1452021. Epub 2018 Apr 1.
• [6] High levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the serum are associated with poor prognosis in HPV-negative squamous cell oropharyngeal cancer.Cancer Immunol Immunother. 2019 Aug;68(8):1263-1272. doi: 10.1007/s00262-019-02362-4. Epub 2019 Jun 25.
• [7] Urine Levels of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Children with Type 1 Diabetes Mellitus.J Clin Res Pediatr Endocrinol. 2019 May 28;11(2):157-163. doi: 10.4274/jcrpe.galenos.2018.2018.0221. Epub 2018 Nov 6.
• [8] Investigation of the molecular mechanisms preceding PDE4 inhibitor-induced vasculopathy in rats: tissue inhibitor of metalloproteinase 1, a potential predictive biomarker.Toxicol Sci. 2007 Nov;100(1):238-47. doi: 10.1093/toxsci/kfm161. Epub 2007 Jun 14.
• [9] Protective effect of genistein isolated from Hydrocotyle sibthorpioides on hepatic injury and fibrosis induced by chronic alcohol in rats.Toxicol Lett. 2013 Feb 27;217(2):102-10. doi: 10.1016/j.toxlet.2012.12.014. Epub 2012 Dec 26.
• [10] Identification of Blood Biomarkers for Alzheimer's Disease Through Computational Prediction and Experimental Validation.Front Neurol. 2019 Jan 8;9:1158. doi: 10.3389/fneur.2018.01158. eCollection 2018.
• [11] Co-expression of TIMP-1 and its cell surface binding partner CD63 in glioblastomas.BMC Cancer. 2018 Mar 9;18(1):270. doi: 10.1186/s12885-018-4179-y.
• [12] Electronegative LDL induces MMP-9 and TIMP-1 release in monocytes through CD14 activation: Inhibitory effect of glycosaminoglycan sulodexide.Biochim Biophys Acta Mol Basis Dis. 2018 Dec;1864(12):3559-3567. doi: 10.1016/j.bbadis.2018.09.022. Epub 2018 Sep 19.
• [13] The Balance of Tissue Inhibitor of Metalloproteinase-1 and Matrix Metalloproteinase-9 in the Autoimmune Inner Ear Disease Patients.J Interferon Cytokine Res. 2017 Aug;37(8):354-361. doi: 10.1089/jir.2017.0053. Epub 2017 Jul 11.
• [14] Tumor tissue inhibitor of metalloproteinases-1 (TIMP-1) in hormone-independent breast cancer might originate in stromal cells, and improves stratification of prognosis together with nodal status.Exp Cell Res. 2012 Jun 10;318(10):1094-103. doi: 10.1016/j.yexcr.2012.03.009. Epub 2012 Mar 23.
• [15] Proteolytic biomarkers are related to prognosis in COPD- report from a population-based cohort.Respir Res. 2018 Apr 12;19(1):64. doi: 10.1186/s12931-018-0772-5.
• [16] Toxicogenomic analysis reveals profibrogenic effects of trichloroethylene in autoimmune-mediated cholangitis in mice.Toxicol Sci. 2014 Oct;141(2):515-23. doi: 10.1093/toxsci/kfu148. Epub 2014 Jul 23.
• [17] Tissue inhibitor of metalloproteinase-1 messenger RNA expression is enhanced relative to interstitial collagenase messenger RNA in experimental liver injury and fibrosis.Hepatology. 1996 Jul;24(1):176-84. doi: 10.1002/hep.510240129.
• [18] Ca(2+)/calmodulin-dependent protein kinase II regulates colon cancer proliferation and migration via ERK1/2 and p38 pathways.World J Gastroenterol. 2017 Sep 7;23(33):6111-6118. doi: 10.3748/wjg.v23.i33.6111.
• [19] Prognostic values of matrix metalloproteinase family expression in human colorectal carcinoma.J Surg Res. 2008 May 1;146(1):32-42. doi: 10.1016/j.jss.2007.02.011. Epub 2007 May 31.
• [20] Overexpression of TIMP-1 and Sensitivity to Topoisomerase Inhibitors in Glioblastoma Cell Lines.Pathol Oncol Res. 2019 Jan;25(1):59-69. doi: 10.1007/s12253-017-0312-5. Epub 2017 Sep 30.
• [21] Melatonin maximizes the therapeutic potential of non-preconditioned MSCs in a DEN-induced rat model of HCC.Biomed Pharmacother. 2019 Jun;114:108732. doi: 10.1016/j.biopha.2019.108732. Epub 2019 Mar 27.
• [22] MMP-9 and TIMP-1 in placenta of hypertensive disorder complicating pregnancy.Exp Ther Med. 2019 Jul;18(1):637-641. doi: 10.3892/etm.2019.7591. Epub 2019 May 17.
• [23] Analysis of the differential urinary protein profile in IgA nephropathy patients of Uygur ethnicity.BMC Nephrol. 2018 Dec 14;19(1):358. doi: 10.1186/s12882-018-1139-3.
• [24] Role of extracellular matrix remodelling gene SNPs in keratoconus.Br J Biomed Sci. 2020 Jan;77(1):13-18. doi: 10.1080/09674845.2019.1654346. Epub 2019 Aug 29.
• [25] Role of matrix metalloproteinases and their inhibitors in the development of cervical metastases in papillary thyroid cancer.Clin Otolaryngol. 2020 Jan;45(1):55-62. doi: 10.1111/coa.13466. Epub 2019 Nov 13.
• [26] Orthologous proteins of experimental de- and remyelination are differentially regulated in the CSF proteome of multiple sclerosis subtypes.PLoS One. 2018 Aug 16;13(8):e0202530. doi: 10.1371/journal.pone.0202530. eCollection 2018.
• [27] The impact of age on cardiac function and extracellular matrix component expression in adverse post-infarction remodeling in mice.Exp Gerontol. 2019 May;119:193-202. doi: 10.1016/j.exger.2019.02.008. Epub 2019 Feb 11.
• [28] Effects of Controlling Abnormal Joint Movement on Expression of MMP13 and TIMP-1 in Osteoarthritis.Cartilage. 2020 Jan;11(1):98-107. doi: 10.1177/1947603518783449. Epub 2018 Jun 25.
• [29] Elevated systemic levels of the matrix metalloproteinase inhibitor TIMP-1 correlate with clinical markers of cachexia in patients with chronic pancreatitis and pancreatic cancer.BMC Cancer. 2018 Feb 2;18(1):128. doi: 10.1186/s12885-018-4055-9.
• [30] Therapeutic effects of obeticholic acid (OCA) treatment in a bleomycin-induced pulmonary fibrosis rat model.J Endocrinol Invest. 2019 Mar;42(3):283-294. doi: 10.1007/s40618-018-0913-1. Epub 2018 Jun 19.
• [31] MMP-8 and TIMP-1 are associated to periodontal inflammation in patients with rheumatoid arthritis under methotrexate immunosuppression - First results of a cross-sectional study.J Microbiol Immunol Infect. 2019 Jun;52(3):386-394. doi: 10.1016/j.jmii.2017.07.016. Epub 2017 Sep 4.
• [32] Effect of simvastatin on MMPs and TIMPs in human brain endothelial cells and experimental stroke.Transl Stroke Res. 2015 Apr;6(2):156-9. doi: 10.1007/s12975-014-0381-7. Epub 2014 Dec 5.
• [33] Attenuation of aquaporin-3 and epidermal growth factor receptor expression and activation in systemic sclerosis dermal fibroblasts.J Cell Physiol. 2019 Aug;234(8):12876-12883. doi: 10.1002/jcp.27952. Epub 2018 Dec 7.
• [34] BRAFV600E mutation, TIMP-1 upregulation, and NF-B activation: closing the loop on the papillary thyroid cancer trilogy.Endocr Relat Cancer. 2011 Nov 14;18(6):669-85. doi: 10.1530/ERC-11-0076. Print 2011 Dec.
• [35] Elevated copper impairs hepatic nuclear receptor function in Wilson's disease.J Clin Invest. 2015 Sep;125(9):3449-60. doi: 10.1172/JCI78991. Epub 2015 Aug 4.
• [36] Raloxifene attenuates Gas6 and apoptosis in experimental aortic valve disease in renal failure.Am J Physiol Heart Circ Physiol. 2011 May;300(5):H1829-40. doi: 10.1152/ajpheart.00240.2010. Epub 2011 Feb 18.
• [37] Spatial and temporal pattern of expression of interstitial collagenase, stromelysin/transin, gelatinase A, and TIMP-1 during experimental gastric ulcer healing.Digestion. 2004;70(2):127-38. doi: 10.1159/000080931. Epub 2004 Sep 16.
• [38] MicroRNA and mRNA expression profiling in rat acute respiratory distress syndrome.BMC Med Genomics. 2014 Jul 28;7:46. doi: 10.1186/1755-8794-7-46.
• [39] SCCRO (DCUN1D1) induces extracellular matrix invasion by activating matrix metalloproteinase 2.Clin Cancer Res. 2008 Nov 1;14(21):6780-9. doi: 10.1158/1078-0432.CCR-08-0719.
• [40] Identification of differentially expressed genes in human varicose veins: involvement of matrix gla protein in extracellular matrix remodeling.J Vasc Res. 2007;44(6):444-59. doi: 10.1159/000106189. Epub 2007 Jul 20.
• [41] 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.
• [42] Phenytoin and cyclosporin A suppress the expression of MMP-1, TIMP-1, and cathepsin L, but not cathepsin B in cultured gingival fibroblasts. J Periodontol. 2000 Jun;71(6):955-60. doi: 10.1902/jop.2000.71.6.955.
• [43] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [44] 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.
• [45] 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.
• [46] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [47] In vitro evaluation of biomarkers for cisplatin-induced nephrotoxicity using HK-2 human kidney epithelial cells. Toxicol Lett. 2013 Mar 13;217(3):235-42. doi: 10.1016/j.toxlet.2012.12.015. Epub 2012 Dec 31.
• [48] Analysis of estrogen agonism and antagonism of tamoxifen, raloxifene, and ICI182780 in endometrial cancer cells: a putative role for the epidermal growth factor receptor ligand amphiregulin. J Soc Gynecol Investig. 2005 Oct;12(7):e55-67.
• [49] 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.
• [50] Dietary supplementation with the anti-tumour promoter quercetin: its effects on matrix metalloproteinase gene regulation. Mutat Res. 2001 Sep 1;480-481:269-76. doi: 10.1016/s0027-5107(01)00184-1.
• [51] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [52] Arsenic trioxide (As2O3) inhibits invasion of HT1080 human fibrosarcoma cells: role of nuclear factor-kappaB and reactive oxygen species. J Cell Biochem. 2005 Aug 1;95(5):955-69. doi: 10.1002/jcb.20452.
• [53] Triclosan and bisphenol a affect decidualization of human endometrial stromal cells. Mol Cell Endocrinol. 2016 Feb 15;422:74-83. doi: 10.1016/j.mce.2015.11.017. Epub 2015 Nov 19.
• [54] R(+)-methanandamide and other cannabinoids induce the expression of cyclooxygenase-2 and matrix metalloproteinases in human nonpigmented ciliary epithelial cells. J Pharmacol Exp Ther. 2006 Mar;316(3):1219-28.
• [55] Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
• [56] Inhibition of invasion and induction of apoptosis by selenium in human malignant brain tumour cells in vitro. Int J Oncol. 2007 May;30(5):1263-71.
• [57] The impact of luteal phase support on gene expression of extracellular matrix protein and adhesion molecules in the human endometrium during the window of implantation following controlled ovarian stimulation with a GnRH antagonist protocol. Fertil Steril. 2010 Nov;94(6):2264-71. doi: 10.1016/j.fertnstert.2010.01.068. Epub 2010 Mar 12.
• [58] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [59] Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1. FASEB J. 2012 Apr;26(4):1535-48. doi: 10.1096/fj.11-198184. Epub 2011 Dec 23.
• [60] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [61] 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.
• [62] Aspirin inhibits MMP-2 and MMP-9 expressions and activities through upregulation of PPARalpha/gamma and TIMP gene expressions in ox-LDL-stimulated macrophages derived from human monocytes. Pharmacology. 2009;83(1):18-25. doi: 10.1159/000166183. Epub 2008 Oct 30.
• [63] Effects of nicotine and lipopolysaccharide on the expression of matrix metalloproteinases, plasminogen activators, and their inhibitors in human osteoblasts. Arch Oral Biol. 2009 Feb;54(2):146-55.
• [64] Matrix metalloproteinase (MMP)-2 and MMP-9 and their inhibitor, TIMP-1, in human term decidua and fetal membranes: the effect of prostaglandin F(2alpha) and indomethacin. Mol Hum Reprod. 2001 Dec;7(12):1187-93. doi: 10.1093/molehr/7.12.1187.
• [65] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [66] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [67] Discovery of molecular mechanisms of neuroprotection using cell-based bioassays and oligonucleotide arrays. Physiol Genomics. 2002 Oct 29;11(2):45-52. doi: 10.1152/physiolgenomics.00064.2002.
• [68] Capsaicin promotes a more aggressive gene expression phenotype and invasiveness in null-TRPV1 urothelial cancer cells. Carcinogenesis. 2011 May;32(5):686-94. doi: 10.1093/carcin/bgr025. Epub 2011 Feb 10.
• [69] Ascorbic acid induces collagenase-1 in human periodontal ligament cells but not in MC3T3-E1 osteoblast-like cells: potential association between collagenase expression and changes in alkaline phosphatase phenotype. J Bone Miner Res. 2003 Jan;18(1):67-77. doi: 10.1359/jbmr.2003.18.1.67.
• [70] 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.
• [71] Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo. Toxicol Appl Pharmacol. 2014 Jan 15;274(2):302-12.
• [72] Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway. Biomed Pharmacother. 2019 Jan;109:2043-2053. doi: 10.1016/j.biopha.2018.11.030. Epub 2018 Nov 26.
• [73] 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is up-regulated by flurbiprofen and other non-steroidal anti-inflammatory drugs in human colon cancer HT29 cells. Arch Biochem Biophys. 2009 Jul 15;487(2):139-45. doi: 10.1016/j.abb.2009.05.017. Epub 2009 Jun 6.
• [74] Effect of lamivudine treatment on plasma levels of transforming growth factor beta1, tissue inhibitor of metalloproteinases-1 and metalloproteinase-1 in patients with chronic hepatitis B. World J Gastroenterol. 2004 Sep 15;10(18):2661-5. doi: 10.3748/wjg.v10.i18.2661.
• [75] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [76] Inhaled corticosteroids decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in asthma. J Allergy Clin Immunol. 1999 Aug;104(2 Pt 1):356-63. doi: 10.1016/s0091-6749(99)70379-9.
• [77] Resveratrol modulates the angiogenic response to exercise training in skeletal muscles of aged men. Am J Physiol Heart Circ Physiol. 2014 Oct 15;307(8):H1111-9. doi: 10.1152/ajpheart.00168.2014. Epub 2014 Aug 15.
• [78] Anti-inflammatory effect of curcumin involves downregulation of MMP-9 in blood mononuclear cells. Int Immunopharmacol. 2007 Dec 15;7(13):1659-67. doi: 10.1016/j.intimp.2007.08.018. Epub 2007 Sep 14.
• [79] Genistein suppresses the invasive potential of human breast cancer cells through transcriptional regulation of metalloproteinases and their tissue inhibitors. Int J Oncol. 2005 Apr;26(4):1101-9. doi: 10.3892/ijo.26.4.1101.
• [80] Inhibition of NF-B and metastasis in irinotecan (CPT-11)-resistant LoVo colon cancer cells by thymoquinone via JNK and p38. Environ Toxicol. 2017 Feb;32(2):669-678. doi: 10.1002/tox.22268. Epub 2016 Apr 5.
• [81] Flavonoid glycosides isolated from Salicornia herbacea inhibit matrix metalloproteinase in HT1080 cells. Toxicol In Vitro. 2008 Oct;22(7):1742-8. doi: 10.1016/j.tiv.2008.07.013. Epub 2008 Jul 31.
• [82] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [83] Quercetin inhibits matrix metalloproteinase-1 expression in human vascular endothelial cells through extracellular signal-regulated kinase. Arch Biochem Biophys. 2001 Jul 1;391(1):72-8. doi: 10.1006/abbi.2001.2402.
• [84] 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.
• [85] The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models. Oncogene. 2016 Feb 18;35(7):833-45.
• [86] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [87] Oral submucous fibrosis: review on aetiology and pathogenesis. Oral Oncol. 2006 Jul;42(6):561-8.
• [88] Inhibition of cell proliferation, invasion, tumor growth and metastasis by an oral non-antimicrobial tetracycline analog (COL-3) in a metastatic prostate cancer model. Int J Cancer. 2002 Mar 10;98(2):297-309. doi: 10.1002/ijc.10168.
• [89] 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.
• [90] A novel circular RNA confers trastuzumab resistance in human epidermal growth factor receptor 2-positive breast cancer through regulating ferroptosis. Environ Toxicol. 2022 Jul;37(7):1597-1607. doi: 10.1002/tox.23509. Epub 2022 Mar 2.
• [91] The effect of bisphenol a exposure onto endothelial and decidualized stromal cells on regulation of the invasion ability of trophoblastic spheroids in in?vitro co-culture model. Biochem Biophys Res Commun. 2019 Aug 20;516(2):506-514. doi: 10.1016/j.bbrc.2019.06.066. Epub 2019 Jun 21.
• [92] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [93] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [94] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [95] Deguelin inhibits the migration and invasion of U-2 OS human osteosarcoma cells via the inhibition of matrix metalloproteinase-2/-9 in vitro. Molecules. 2014 Oct 15;19(10):16588-608.
• [96] Methylparaben-induced decrease in collagen production and viability of cultured human dermal fibroblasts. J Appl Toxicol. 2017 Sep;37(9):1117-1124. doi: 10.1002/jat.3466. Epub 2017 Apr 6.
• [97] Paraquat exposure induces Parkinsonism by altering lipid profile and evoking neuroinflammation in the midbrain. Environ Int. 2022 Nov;169:107512. doi: 10.1016/j.envint.2022.107512. Epub 2022 Sep 8.
• [98] Calorie restriction-induced changes in the secretome of human adipocytes, comparison with resveratrol-induced secretome effects. Biochim Biophys Acta. 2014 Sep;1844(9):1511-22. doi: 10.1016/j.bbapap.2014.04.023. Epub 2014 May 5.
• [99] Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust. Clin Exp Otorhinolaryngol. 2015 Dec;8(4):345-53. doi: 10.3342/ceo.2015.8.4.345. Epub 2015 Nov 10.
• [100] 4-Hydroxynonenal as a selective pro-fibrogenic stimulus for activated human hepatic stellate cells. J Hepatol. 2004 Jan;40(1):60-8. doi: 10.1016/s0168-8278(03)00480-x.
• [101] Sorafenib reduces steatosis-induced fibrogenesis in a human 3D co-culture model of non-alcoholic fatty liver disease. Environ Toxicol. 2021 Feb;36(2):168-176. doi: 10.1002/tox.23021. Epub 2020 Sep 12.
• [102] Mechanisms of induction of human tissue inhibitor of metalloproteinases-1 (TIMP-1) gene expression by all-trans retinoic acid in combination with basic fibroblast growth factor. Eur J Biochem. 2000 Jul;267(13):4150-6. doi: 10.1046/j.1432-1327.2000.01459.x.
• [103] Long-term acetaminophen treatment induced liver fibrosis in mice and the involvement of Egr-1. Toxicology. 2017 May 1;382:47-58. doi: 10.1016/j.tox.2017.03.008. Epub 2017 Mar 9.
• [104] BRD4 is a novel therapeutic target for liver fibrosis. Proc Natl Acad Sci U S A. 2015 Dec 22;112(51):15713-8. doi: 10.1073/pnas.1522163112. Epub 2015 Dec 7.
• [105] Rolipram suppresses migration and invasion of human choriocarcinoma cells by inhibiting phosphodiesterase 4-mediated epithelial-mesenchymal transition. J Biochem Mol Toxicol. 2023 Jul;37(7):e23363. doi: 10.1002/jbt.23363. Epub 2023 Apr 5.
• [106] In vitro and ex vivo anti-fibrotic effects of LY2109761, a small molecule inhibitor against TGF-. Toxicol Appl Pharmacol. 2018 Sep 15;355:127-137. doi: 10.1016/j.taap.2018.07.001. Epub 2018 Jul 3.
• [107] Arg-Gly-Asp (RGD) peptide ameliorates carbon tetrachloride-induced liver fibrosis via inhibition of collagen production and acceleration of collagenase activity. Int J Mol Med. 2004 Dec;14(6):1049-53.
• [108] Trichloroethanol up-regulates matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in HaCaT cells. Toxicol In Vitro. 2011 Dec;25(8):1638-43. doi: 10.1016/j.tiv.2011.06.015. Epub 2011 Jun 30.
• [109] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.