Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTW0267)

• DOT Name: Lipoprotein lipase (LPL)
• Synonyms: LPL; EC 3.1.1.34; Phospholipase A1; EC 3.1.1.32
• Gene Name: LPL
• Related Disease:
  Familial lipoprotein lipase deficiency
  Hyperlipidemia, familial combined, LPL related
• UniProt ID: LIPL_HUMAN
• PDB ID: 6E7K; 6OAU; 6OAZ; 6OB0; 6WN4
• EC Number: 3.1.1.32; 3.1.1.34
• Pfam ID: PF00151 ; PF01477
• Sequence:
  MESKALLVLTLAVWLQSLTASRGGVAAADQRRDFIDIESKFALRTPEDTAEDTCHLIPGV
  AESVATCHFNHSSKTFMVIHGWTVTGMYESWVPKLVAALYKREPDSNVIVVDWLSRAQEH
  YPVSAGYTKLVGQDVARFINWMEEEFNYPLDNVHLLGYSLGAHAAGIAGSLTNKKVNRIT
  GLDPAGPNFEYAEAPSRLSPDDADFVDVLHTFTRGSPGRSIGIQKPVGHVDIYPNGGTFQ
  PGCNIGEAIRVIAERGLGDVDQLVKCSHERSIHLFIDSLLNEENPSKAYRCSSKEAFEKG
  LCLSCRKNRCNNLGYEINKVRAKRSSKMYLKTRSQMPYKVFHYQVKIHFSGTESETHTNQ
  AFEISLYGTVAESENIPFTLPEVSTNKTYSFLIYTEVDIGELLMLKLKWKSDSYFSWSDW
  WSSPGFAIQKIRVKAGETQKKVIFCSREKVSHLQKGKAPAVFVKCHDKSLNKKSG
• Function: Key enzyme in triglyceride metabolism. Catalyzes the hydrolysis of triglycerides from circulating chylomicrons and very low density lipoproteins (VLDL), and thereby plays an important role in lipid clearance from the blood stream, lipid utilization and storage. Although it has both phospholipase and triglyceride lipase activities it is primarily a triglyceride lipase with low but detectable phospholipase activity. Mediates margination of triglyceride-rich lipoprotein particles in capillaries. Recruited to its site of action on the luminal surface of vascular endothelium by binding to GPIHBP1 and cell surface heparan sulfate proteoglycans.
• Tissue Specificity: Detected in blood plasma . Detected in milk (at protein level) .
• KEGG Pathway:
  Glycerolipid metabolism (hsa00561)
  PPAR sig.ling pathway (hsa03320)
  Cholesterol metabolism (hsa04979)
  Alzheimer disease (hsa05010)
• Reactome Pathway:
  Assembly of active LPL and LIPC lipase complexes (R-HSA-8963889)
  Chylomicron remodeling (R-HSA-8963901)
  Retinoid metabolism and transport (R-HSA-975634)
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial lipoprotein lipase deficiency	DIS0M7NJ	Definitive	Autosomal recessive	[1]
Hyperlipidemia, familial combined, LPL related	DISL1CE3	Strong	Autosomal dominant	[1]

This DOT Affected the Drug Response of 11 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Lipoprotein lipase (LPL) increases the Vascular disorders ADR of Paclitaxel.	[43]
Ritonavir	DMU764S	Approved	Lipoprotein lipase (LPL) increases the Insulin resistance ADR of Ritonavir.	[43]
Etretinate	DM2CZFA	Approved	Lipoprotein lipase (LPL) increases the Lipid metabolism disorders ADR of Etretinate.	[43]
Adenosine triphosphate	DM79F6G	Approved	Lipoprotein lipase (LPL) affects the response to substance of Adenosine triphosphate.	[44]
Phenylephrine	DMZHUO5	Approved	Lipoprotein lipase (LPL) affects the response to substance of Phenylephrine.	[44]
Furosemide	DMMQ8ZG	Approved	Lipoprotein lipase (LPL) increases the Renal failure ADR of Furosemide.	[43]
Acetylcholine	DMDF79Z	Approved	Lipoprotein lipase (LPL) affects the response to substance of Acetylcholine.	[44]
Indinavir	DM0T3YH	Approved	Lipoprotein lipase (LPL) increases the Insulin resistance ADR of Indinavir.	[43]
Potassium chloride	DMMTAJC	Approved	Lipoprotein lipase (LPL) increases the response to substance of Potassium chloride.	[44]
Amprenavir	DMLMXE0	Approved	Lipoprotein lipase (LPL) increases the Insulin resistance ADR of Amprenavir.	[43]
VRX496	DMIO4V5	Approved	Lipoprotein lipase (LPL) increases the Insulin resistance ADR of VRX496.	[43]

47 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 Lipoprotein lipase (LPL).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Lipoprotein lipase (LPL).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lipoprotein lipase (LPL).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Lipoprotein lipase (LPL).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Lipoprotein lipase (LPL).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Lipoprotein lipase (LPL).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Lipoprotein lipase (LPL).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Lipoprotein lipase (LPL).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Lipoprotein lipase (LPL).	[10]
Marinol	DM70IK5	Approved	Marinol increases the expression of Lipoprotein lipase (LPL).	[11]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Lipoprotein lipase (LPL).	[6]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Lipoprotein lipase (LPL).	[12]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Lipoprotein lipase (LPL).	[13]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Lipoprotein lipase (LPL).	[14]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Lipoprotein lipase (LPL).	[15]
Zidovudine	DM4KI7O	Approved	Zidovudine decreases the expression of Lipoprotein lipase (LPL).	[16]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Lipoprotein lipase (LPL).	[17]
Bezafibrate	DMZDCS0	Approved	Bezafibrate increases the activity of Lipoprotein lipase (LPL).	[18]
Melatonin	DMKWFBT	Approved	Melatonin decreases the expression of Lipoprotein lipase (LPL).	[19]
Orlistat	DMRJSP8	Approved	Orlistat decreases the activity of Lipoprotein lipase (LPL).	[20]
Hesperetin	DMKER83	Approved	Hesperetin decreases the expression of Lipoprotein lipase (LPL).	[21]
Nevirapine	DM6HX9B	Approved	Nevirapine increases the expression of Lipoprotein lipase (LPL).	[22]
Efavirenz	DMC0GSJ	Approved	Efavirenz decreases the expression of Lipoprotein lipase (LPL).	[22]
Benzbromarone	DMC3YUA	Approved	Benzbromarone increases the expression of Lipoprotein lipase (LPL).	[23]
Ciprofibrate	DMGC5DB	Approved	Ciprofibrate increases the activity of Lipoprotein lipase (LPL).	[24]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Lipoprotein lipase (LPL).	[9]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Lipoprotein lipase (LPL).	[25]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Lipoprotein lipase (LPL).	[26]
ANW-32821	DMMJOZD	Phase 2	ANW-32821 increases the expression of Lipoprotein lipase (LPL).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Lipoprotein lipase (LPL).	[28]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Lipoprotein lipase (LPL).	[29]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Lipoprotein lipase (LPL).	[30]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Lipoprotein lipase (LPL).	[31]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Lipoprotein lipase (LPL).	[33]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Lipoprotein lipase (LPL).	[34]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of Lipoprotein lipase (LPL).	[35]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Lipoprotein lipase (LPL).	[15]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Lipoprotein lipase (LPL).	[36]
GW-3965	DMG60ET	Investigative	GW-3965 increases the expression of Lipoprotein lipase (LPL).	[36]
MANGIFERIN	DMWAF5Z	Investigative	MANGIFERIN increases the expression of Lipoprotein lipase (LPL).	[37]
Hydroxydimethylarsine Oxide	DMPS2B1	Investigative	Hydroxydimethylarsine Oxide decreases the expression of Lipoprotein lipase (LPL).	[38]
T0901317	DMZQVDI	Investigative	T0901317 increases the expression of Lipoprotein lipase (LPL).	[17]
25-hydroxycholesterol	DMCHAQ7	Investigative	25-hydroxycholesterol decreases the expression of Lipoprotein lipase (LPL).	[39]
BADGE	DMCK5DG	Investigative	BADGE increases the expression of Lipoprotein lipase (LPL).	[40]
isobutylmethylxanthine	DM46F5X	Investigative	isobutylmethylxanthine increases the expression of Lipoprotein lipase (LPL).	[41]
7alpha-hydroxycholesterol	DMH6LD0	Investigative	7alpha-hydroxycholesterol decreases the expression of Lipoprotein lipase (LPL).	[39]
T0070907	DMTKSVO	Investigative	T0070907 decreases the expression of Lipoprotein lipase (LPL).	[42]

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 Lipoprotein lipase (LPL).	[32]

References

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