Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZY5SC9)

• DOT Name: Hepatic triacylglycerol lipase (LIPC)
• Synonyms: HL; Hepatic lipase; EC 3.1.1.3; Lipase member C; Lysophospholipase; EC 3.1.1.5; Phospholipase A1; EC 3.1.1.32
• Gene Name: LIPC
• Related Disease:
  Cerebrovascular disease
  Hyperlipoproteinemia
  Advanced cancer
  Arteriosclerosis
  Atrial fibrillation
  Cardiac failure
  Cardiovascular disease
  Chronic renal failure
  Classic Hodgkin lymphoma
  Colon cancer
  Colon carcinoma
  Coronary atherosclerosis
  End-stage renal disease
  Familial hypercholesterolemia
  Focal segmental glomerulosclerosis
  High blood pressure
  Hyperalphalipoproteinemia
  Hypercholesterolemia, autosomal dominant, type B
  Hypercholesterolemia, familial, 1
  Hyperinsulinemia
  Hyperlipidemia
  Hyperlipidemia due to hepatic triglyceride lipase deficiency
  Hyperlipidemia, familial combined, LPL related
  Hypertension, pregnancy-induced
  Hypothyroidism
  Myocardial infarction
  Myocardial ischemia
  Neoplasm
  Neovascular age-related macular degeneration
  Nephropathy
  Nephrotic syndrome
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Peripheral arterial disease
  Pre-eclampsia
  Stroke
  Type-1/2 diabetes
  Vascular disease
  Coronary heart disease
  Diabetic kidney disease
  Obesity
  Type-1 diabetes
  Atherosclerosis
  Glycogen storage disease type II
  Ischemia
  Schizophrenia
• UniProt ID: LIPC_HUMAN
• EC Number: 3.1.1.3; 3.1.1.32; 3.1.1.5
• Pfam ID: PF00151 ; PF01477
• Sequence:
  MDTSPLCFSILLVLCIFIQSSALGQSLKPEPFGRRAQAVETNKTLHEMKTRFLLFGETNQ
  GCQIRINHPDTLQECGFNSSLPLVMIIHGWSVDGVLENWIWQMVAALKSQPAQPVNVGLV
  DWITLAHDHYTIAVRNTRLVGKEVAALLRWLEESVQLSRSHVHLIGYSLGAHVSGFAGSS
  IGGTHKIGRITGLDAAGPLFEGSAPSNRLSPDDANFVDAIHTFTREHMGLSVGIKQPIGH
  YDFYPNGGSFQPGCHFLELYRHIAQHGFNAITQTIKCSHERSVHLFIDSLLHAGTQSMAY
  PCGDMNSFSQGLCLSCKKGRCNTLGYHVRQEPRSKSKRLFLVTRAQSPFKVYHYQFKIQF
  INQTETPIQTTFTMSLLGTKEKMQKIPITLGKGIASNKTYSFLITLDVDIGELIMIKFKW
  ENSAVWANVWDTVQTIIPWSTGPRHSGLVLKTIRVKAGETQQRMTFCSENTDDLLLRPTQ
  EKIFVKCEIKSKTSKRKIR
• Function: Catalyzes the hydrolysis of triglycerides and phospholipids present in circulating plasma lipoproteins, including chylomicrons, intermediate density lipoproteins (IDL), low density lipoproteins (LDL) of large size and high density lipoproteins (HDL), releasing free fatty acids (FFA) and smaller lipoprotein particles. Also exhibits lysophospholipase activity. Can hydrolyze both neutral lipid and phospholipid substrates but shows a greater binding affinity for neutral lipid substrates than phospholipid substrates. In native LDL, preferentially hydrolyzes the phosphatidylcholine species containing polyunsaturated fatty acids at sn-2 position.
• KEGG Pathway:
  Glycerolipid metabolism (hsa00561)
  Metabolic pathways (hsa01100)
  Cholesterol metabolism (hsa04979)
• Reactome Pathway:
  Chylomicron clearance (R-HSA-8964026)
  Assembly of active LPL and LIPC lipase complexes (R-HSA-8963889)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebrovascular disease	DISAB237	Definitive	Genetic Variation	[1]
Hyperlipoproteinemia	DISVBLBO	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[4]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[5]
Cardiac failure	DISDC067	Strong	Genetic Variation	[5]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[6]
Chronic renal failure	DISGG7K6	Strong	Biomarker	[7]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Genetic Variation	[8]
Colon cancer	DISVC52G	Strong	Altered Expression	[9]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[9]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[10]
End-stage renal disease	DISXA7GG	Strong	Biomarker	[7]
Familial hypercholesterolemia	DISC06IX	Strong	Posttranslational Modification	[11]
Focal segmental glomerulosclerosis	DISJNHH0	Strong	Biomarker	[12]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[13]
Hyperalphalipoproteinemia	DISPUX00	Strong	Genetic Variation	[14]
Hypercholesterolemia, autosomal dominant, type B	DISNFXJZ	Strong	Biomarker	[15]
Hypercholesterolemia, familial, 1	DISU411W	Strong	Posttranslational Modification	[11]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[16]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[17]
Hyperlipidemia due to hepatic triglyceride lipase deficiency	DISA68R2	Strong	Autosomal recessive	[18]
Hyperlipidemia, familial combined, LPL related	DISL1CE3	Strong	Genetic Variation	[19]
Hypertension, pregnancy-induced	DISHNU25	Strong	Genetic Variation	[20]
Hypothyroidism	DISR0H6D	Strong	Biomarker	[21]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[22]
Myocardial ischemia	DISFTVXF	Strong	Genetic Variation	[23]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Neovascular age-related macular degeneration	DIS5S9R7	Strong	Genetic Variation	[24]
Nephropathy	DISXWP4P	Strong	Genetic Variation	[25]
Nephrotic syndrome	DISSPSC2	Strong	Biomarker	[26]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[27]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[3]
Peripheral arterial disease	DIS78WFB	Strong	Genetic Variation	[28]
Pre-eclampsia	DISY7Q29	Strong	Genetic Variation	[29]
Stroke	DISX6UHX	Strong	Genetic Variation	[5]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[5]
Vascular disease	DISVS67S	Strong	Genetic Variation	[30]
Coronary heart disease	DIS5OIP1	moderate	Altered Expression	[11]
Diabetic kidney disease	DISJMWEY	moderate	Genetic Variation	[25]
Obesity	DIS47Y1K	moderate	Biomarker	[31]
Type-1 diabetes	DIS7HLUB	moderate	Biomarker	[32]
Atherosclerosis	DISMN9J3	Limited	Biomarker	[4]
Glycogen storage disease type II	DISXZPBC	Limited	Biomarker	[33]
Ischemia	DIS5XOOY	Limited	Biomarker	[34]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Hepatic triacylglycerol lipase (LIPC).	[36]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Hepatic triacylglycerol lipase (LIPC).	[42]

17 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 Hepatic triacylglycerol lipase (LIPC).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Hepatic triacylglycerol lipase (LIPC).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Hepatic triacylglycerol lipase (LIPC).	[39]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Hepatic triacylglycerol lipase (LIPC).	[40]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Hepatic triacylglycerol lipase (LIPC).	[41]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Hepatic triacylglycerol lipase (LIPC).	[43]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Hepatic triacylglycerol lipase (LIPC).	[44]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Hepatic triacylglycerol lipase (LIPC).	[45]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Hepatic triacylglycerol lipase (LIPC).	[46]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Hepatic triacylglycerol lipase (LIPC).	[47]
Bezafibrate	DMZDCS0	Approved	Bezafibrate increases the activity of Hepatic triacylglycerol lipase (LIPC).	[48]
CS-038	DM67P0F	Phase 3	CS-038 increases the expression of Hepatic triacylglycerol lipase (LIPC).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Hepatic triacylglycerol lipase (LIPC).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Hepatic triacylglycerol lipase (LIPC).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Hepatic triacylglycerol lipase (LIPC).	[50]
Oleic acid	DM54O1Z	Investigative	Oleic acid decreases the expression of Hepatic triacylglycerol lipase (LIPC).	[51]
Farnesol	DMV2X1B	Investigative	Farnesol increases the expression of Hepatic triacylglycerol lipase (LIPC).	[52]

References

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