Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB4Y5RJ)

DOT Name Sterol O-acyltransferase 1 (SOAT1)
Synonyms EC 2.3.1.26; Acyl-coenzyme A:cholesterol acyltransferase 1; ACAT-1; Cholesterol acyltransferase 1
Gene Name SOAT1
Related Disease
Myelofibrosis ( )
Psoriasis ( )
Acute lymphocytic leukaemia ( )
Acute myelogenous leukaemia ( )
Adult glioblastoma ( )
Adult lymphoma ( )
Advanced cancer ( )
Alzheimer disease ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Autoimmune disease ( )
B-cell lymphoma ( )
Breast cancer ( )
Breast carcinoma ( )
Childhood acute lymphoblastic leukemia ( )
Classic Hodgkin lymphoma ( )
Colorectal carcinoma ( )
Diabetic kidney disease ( )
Head-neck squamous cell carcinoma ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Immunodeficiency ( )
Inflammatory bowel disease ( )
leukaemia ( )
Leukemia ( )
Lung cancer ( )
Lung carcinoma ( )
Lymphoma ( )
Myocardial infarction ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Pediatric lymphoma ( )
Plasma cell myeloma ( )
Primary myelofibrosis ( )
Rheumatoid arthritis ( )
Squamous cell carcinoma ( )
Systemic lupus erythematosus ( )
T-cell leukaemia ( )
Crohn disease ( )
Gastric cancer ( )
Pancreatic cancer ( )
Polycythemia vera ( )
Stomach cancer ( )
Type-1/2 diabetes ( )
Glioblastoma multiforme ( )
Myeloproliferative neoplasm ( )
Prostate cancer ( )
Prostate carcinoma ( )
UniProt ID
SOAT1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
6L47; 6L48; 6P2J; 6P2P; 6VUM
EC Number
2.3.1.26
Pfam ID
PF03062
Sequence
MVGEEKMSLRNRLSKSRENPEEDEDQRNPAKESLETPSNGRIDIKQLIAKKIKLTAEAEE
LKPFFMKEVGSHFDDFVTNLIEKSASLDNGGCALTTFSVLEGEKNNHRAKDLRAPPEQGK
IFIARRSLLDELLEVDHIRTIYHMFIALLILFILSTLVVDYIDEGRLVLEFSLLSYAFGK
FPTVVWTWWIMFLSTFSVPYFLFQHWATGYSKSSHPLIRSLFHGFLFMIFQIGVLGFGPT
YVVLAYTLPPASRFIIIFEQIRFVMKAHSFVRENVPRVLNSAKEKSSTVPIPTVNQYLYF
LFAPTLIYRDSYPRNPTVRWGYVAMKFAQVFGCFFYVYYIFERLCAPLFRNIKQEPFSAR
VLVLCVFNSILPGVLILFLTFFAFLHCWLNAFAEMLRFGDRMFYKDWWNSTSYSNYYRTW
NVVVHDWLYYYAYKDFLWFFSKRFKSAAMLAVFAVSAVVHEYALAVCLSFFYPVLFVLFM
FFGMAFNFIVNDSRKKPIWNVLMWTSLFLGNGVLLCFYSQEWYARQHCPLKNPTFLDYVR
PRSWTCRYVF
Function
Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol. Plays a role in lipoprotein assembly and dietary cholesterol absorption. Utilizes oleoyl-CoA ((9Z)-octadecenoyl-CoA) preferentially as susbstrate: shows a higher activity towards an acyl-CoA substrate with a double bond at the delta-9 position (9Z) than towards saturated acyl-CoA or an unsaturated acyl-CoA with a double bond at the delta-7 (7Z) or delta-11 (11Z) positions.
KEGG Pathway
Steroid biosynthesis (hsa00100 )
Cholesterol metabolism (hsa04979 )
Reactome Pathway
LDL clearance (R-HSA-8964038 )
BioCyc Pathway
MetaCyc:HS00706-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Myelofibrosis DISIMP21 Definitive Biomarker [1]
Psoriasis DIS59VMN Definitive Biomarker [2]
Acute lymphocytic leukaemia DISPX75S Strong Altered Expression [3]
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [4]
Adult glioblastoma DISVP4LU Strong Biomarker [5]
Adult lymphoma DISK8IZR Strong Biomarker [6]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Alzheimer disease DISF8S70 Strong Biomarker [5]
Arteriosclerosis DISK5QGC Strong Biomarker [7]
Atherosclerosis DISMN9J3 Strong Biomarker [7]
Autoimmune disease DISORMTM Strong Genetic Variation [8]
B-cell lymphoma DISIH1YQ Strong Biomarker [9]
Breast cancer DIS7DPX1 Strong Biomarker [10]
Breast carcinoma DIS2UE88 Strong Biomarker [10]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Biomarker [11]
Classic Hodgkin lymphoma DISV1LU6 Strong Altered Expression [12]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [13]
Diabetic kidney disease DISJMWEY Strong Biomarker [14]
Head-neck squamous cell carcinoma DISF7P24 Strong Biomarker [15]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [16]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [17]
Immunodeficiency DIS093I0 Strong Biomarker [18]
Inflammatory bowel disease DISGN23E Strong Biomarker [19]
leukaemia DISS7D1V Strong Biomarker [20]
Leukemia DISNAKFL Strong Biomarker [20]
Lung cancer DISCM4YA Strong Biomarker [21]
Lung carcinoma DISTR26C Strong Biomarker [21]
Lymphoma DISN6V4S Strong Biomarker [6]
Myocardial infarction DIS655KI Strong Biomarker [22]
Neoplasm DISZKGEW Strong Biomarker [23]
Non-insulin dependent diabetes DISK1O5Z Strong Biomarker [24]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [21]
Pediatric lymphoma DIS51BK2 Strong Biomarker [6]
Plasma cell myeloma DIS0DFZ0 Strong Biomarker [25]
Primary myelofibrosis DIS6L0CN Strong Biomarker [1]
Rheumatoid arthritis DISTSB4J Strong Biomarker [26]
Squamous cell carcinoma DISQVIFL Strong Biomarker [27]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [28]
T-cell leukaemia DISJ6YIF Strong Biomarker [29]
Crohn disease DIS2C5Q8 moderate Biomarker [30]
Gastric cancer DISXGOUK moderate Biomarker [31]
Pancreatic cancer DISJC981 moderate Biomarker [32]
Polycythemia vera DISB5FPO moderate Altered Expression [33]
Stomach cancer DISKIJSX moderate Biomarker [31]
Type-1/2 diabetes DISIUHAP moderate Biomarker [14]
Glioblastoma multiforme DISK8246 Limited Biomarker [5]
Myeloproliferative neoplasm DIS5KAPA Limited Biomarker [34]
Prostate cancer DISF190Y Limited Biomarker [35]
Prostate carcinoma DISMJPLE Limited Biomarker [35]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Fluorouracil DMUM7HZ Approved Sterol O-acyltransferase 1 (SOAT1) affects the response to substance of Fluorouracil. [50]
Cyclophosphamide DM4O2Z7 Approved Sterol O-acyltransferase 1 (SOAT1) affects the response to substance of Cyclophosphamide. [50]
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13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Sterol O-acyltransferase 1 (SOAT1). [36]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Sterol O-acyltransferase 1 (SOAT1). [37]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Sterol O-acyltransferase 1 (SOAT1). [38]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Sterol O-acyltransferase 1 (SOAT1). [39]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Sterol O-acyltransferase 1 (SOAT1). [40]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Sterol O-acyltransferase 1 (SOAT1). [41]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Sterol O-acyltransferase 1 (SOAT1). [42]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Sterol O-acyltransferase 1 (SOAT1). [43]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Sterol O-acyltransferase 1 (SOAT1). [44]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Sterol O-acyltransferase 1 (SOAT1). [45]
Epanova DMHEAGL Approved Epanova decreases the expression of Sterol O-acyltransferase 1 (SOAT1). [46]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Sterol O-acyltransferase 1 (SOAT1). [47]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Sterol O-acyltransferase 1 (SOAT1). [49]
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⏷ Show the Full List of 13 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Sterol O-acyltransferase 1 (SOAT1). [48]
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References

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7 SOAT1 deficiency attenuates atherosclerosis by regulating inflammation and cholesterol transportation via HO-1 pathway.Biochem Biophys Res Commun. 2018 Jun 22;501(2):343-350. doi: 10.1016/j.bbrc.2018.03.137. Epub 2018 May 11.
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9 STAT3-coordinated migration facilitates the dissemination of diffuse large B-cell lymphomas.Nat Commun. 2018 Sep 12;9(1):3696. doi: 10.1038/s41467-018-06134-z.
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11 Promoter methylation and expression of SOCS3 affect the clinical outcome of pediatric acute lymphoblastic leukemia by JAK/STAT pathway.Biomed Pharmacother. 2019 Jul;115:108913. doi: 10.1016/j.biopha.2019.108913. Epub 2019 May 1.
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13 Overview of the oncogenic signaling pathways in colorectal cancer: Mechanistic insights.Semin Cancer Biol. 2019 Oct;58:65-79. doi: 10.1016/j.semcancer.2019.01.001. Epub 2019 Jan 8.
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25 Abnormal repression of SHP-1, SHP-2 and SOCS-1 transcription sustains the activation of the JAK/STAT3 pathway and the progression of the disease in multiple myeloma.PLoS One. 2017 Apr 3;12(4):e0174835. doi: 10.1371/journal.pone.0174835. eCollection 2017.
26 Systemic treatment with resveratrol alleviates adjuvant arthritis-interstitial lung disease in rats via modulation of JAK/STAT/RANKL signaling pathway.Pulm Pharmacol Ther. 2019 Jun;56:69-74. doi: 10.1016/j.pupt.2019.03.011. Epub 2019 Mar 28.
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32 A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors.Oncologist. 2019 Jan;24(1):14-e10. doi: 10.1634/theoncologist.2017-0665. Epub 2018 Aug 16.
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