Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQL5SPX)

• DOT Name: Angiopoietin-related protein 4 (ANGPTL4)
• Synonyms: Angiopoietin-like protein 4; Hepatic fibrinogen/angiopoietin-related protein; HFARP
• Gene Name: ANGPTL4
• UniProt ID: ANGL4_HUMAN
• PDB ID: 6EUB; 6U0A; 6U1U; 6U73
• Pfam ID: PF00147
• Sequence:
  MSGAPTAGAALMLCAATAVLLSAQGGPVQSKSPRFASWDEMNVLAHGLLQLGQGLREHAE
  RTRSQLSALERRLSACGSACQGTEGSTDLPLAPESRVDPEVLHSLQTQLKAQNSRIQQLF
  HKVAQQQRHLEKQHLRIQHLQSQFGLLDHKHLDHEVAKPARRKRLPEMAQPVDPAHNVSR
  LHRLPRDCQELFQVGERQSGLFEIQPQGSPPFLVNCKMTSDGGWTVIQRRHDGSVDFNRP
  WEAYKAGFGDPHGEFWLGLEKVHSITGDRNSRLAVQLRDWDGNAELLQFSVHLGGEDTAY
  SLQLTAPVAGQLGATTVPPSGLSVPFSTWDQDHDLRRDKNCAKSLSGGWWFGTCSHSNLN
  GQYFRSIPQQRQKLKKGIFWKTWRGRYYPLQATTMLIQPMAAEAAS
• Function: Mediates inactivation of the lipoprotein lipase LPL, and thereby plays a role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism. May also play a role in regulating glucose homeostasis and insulin sensitivity (Probable). Inhibits proliferation, migration, and tubule formation of endothelial cells and reduces vascular leakage. Upon heterologous expression, inhibits the adhesion of endothelial cell to the extracellular matrix (ECM), and inhibits the reorganization of the actin cytoskeleton, formation of actin stress fibers and focal adhesions in endothelial cells that have adhered to ANGPTL4-containing ECM (in vitro). Depending on context, may modulate tumor-related angiogenesis; [ANGPTL4 N-terminal chain]: Mediates inactivation of the lipoprotein lipase LPL, and thereby plays an important role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism. Has higher activity in LPL inactivation than the uncleaved protein.
• Tissue Specificity: Detected in blood plasma (at protein level) . Detected in liver . Detected in white fat tissue and placenta . Expressed at high levels in the placenta, heart, liver, muscle, pancreas and lung but expressed poorly in the brain and kidney.
• KEGG Pathway:
  PPAR sig.ling pathway (hsa03320)
  Cholesterol metabolism (hsa04979)
• Reactome Pathway:
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  Assembly of active LPL and LIPC lipase complexes (R-HSA-8963889)
  Regulation of CDH11 function (R-HSA-9762292)
  PPARA activates gene expression (R-HSA-1989781)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Angiopoietin-related protein 4 (ANGPTL4) affects the response to substance of Fluorouracil.	[39]
Aspirin	DM672AH	Approved	Angiopoietin-related protein 4 (ANGPTL4) increases the Capillary leak syndrome ADR of Aspirin.	[40]

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 Angiopoietin-related protein 4 (ANGPTL4).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Angiopoietin-related protein 4 (ANGPTL4).	[28]

42 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 Angiopoietin-related protein 4 (ANGPTL4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[11]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[12]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[13]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[14]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[15]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[16]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[17]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[7]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[14]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[7]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[7]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[18]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[7]
Vandetanib	DMRICNP	Approved	Vandetanib increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[19]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[20]
Fenfluramine	DM0762O	Phase 3	Fenfluramine decreases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[23]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[24]
GW-501516	DMPL2KM	Discontinued in Phase 4	GW-501516 increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[25]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[26]
Nimesulide	DMR1NMD	Terminated	Nimesulide increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[29]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[30]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[31]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[32]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[33]
Manganese	DMKT129	Investigative	Manganese increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[34]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[35]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[36]
Fibrates	DMFNTMY	Investigative	Fibrates increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[37]
GW0742X	DMGKEO5	Investigative	GW0742X increases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[27]
GSK-0660	DMNIVOX	Investigative	GSK-0660 decreases the expression of Angiopoietin-related protein 4 (ANGPTL4).	[38]

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