Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5CZWKY)

• DOT Name: Platelet glycoprotein 4 (CD36)
• Synonyms: Fatty acid translocase; FAT; Glycoprotein IIIb; GPIIIB; Leukocyte differentiation antigen CD36; PAS IV; PAS-4; Platelet collagen receptor; Platelet glycoprotein IV; GPIV; Thrombospondin receptor; CD antigen CD36
• Gene Name: CD36
• Related Disease: Platelet-type bleeding disorder 10
• UniProt ID: CD36_HUMAN
• PDB ID: 5LGD
• Pfam ID: PF01130
• Sequence:
  MGCDRNCGLIAGAVIGAVLAVFGGILMPVGDLLIQKTIKKQVVLEEGTIAFKNWVKTGTE
  VYRQFWIFDVQNPQEVMMNSSNIQVKQRGPYTYRVRFLAKENVTQDAEDNTVSFLQPNGA
  IFEPSLSVGTEADNFTVLNLAVAAASHIYQNQFVQMILNSLINKSKSSMFQVRTLRELLW
  GYRDPFLSLVPYPVTTTVGLFYPYNNTADGVYKVFNGKDNISKVAIIDTYKGKRNLSYWE
  SHCDMINGTDAASFPPFVEKSQVLQFFSSDICRSIYAVFESDVNLKGIPVYRFVLPSKAF
  ASPVENPDNYCFCTEKIISKNCTSYGVLDISKCKEGRPVYISLPHFLYASPDVSEPIDGL
  NPNEEEHRTYLDIEPITGFTLQFAKRLQVNLLVKPSEKIQVLKNLKRNYIVPILWLNETG
  TIGDEKANMFRSQVTGKINLLGLIEMILLSVGVVMFVAFMISYCACRSKTIK
• Function: Multifunctional glycoprotein that acts as a receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipidic nature such as oxidized low-density lipoprotein (oxLDL), anionic phospholipids, long-chain fatty acids and bacterial diacylated lipopeptides. They are generally multivalent and can therefore engage multiple receptors simultaneously, the resulting formation of CD36 clusters initiates signal transduction and internalization of receptor-ligand complexes. The dependency on coreceptor signaling is strongly ligand specific. Cellular responses to these ligands are involved in angiogenesis, inflammatory response, fatty acid metabolism, taste and dietary fat processing in the intestine (Probable). Binds long-chain fatty acids and facilitates their transport into cells, thus participating in muscle lipid utilization, adipose energy storage, and gut fat absorption. Mechanistically, binding of fatty acids activates downstream kinase LYN, which phosphorylates the palmitoyltransferase ZDHHC5 and inactivates it, resulting in the subsequent depalmitoylation of CD36 and caveolar endocytosis. In the small intestine, plays a role in proximal absorption of dietary fatty acid and cholesterol for optimal chylomicron formation, possibly through the activation of MAPK1/3 (ERK1/2) signaling pathway. Involved in oral fat perception and preferences. Detection into the tongue of long-chain fatty acids leads to a rapid and sustained rise in flux and protein content of pancreatobiliary secretions. In taste receptor cells, mediates the induction of an increase in intracellular calcium levels by long-chain fatty acids, leading to the activation of the gustatory neurons in the nucleus of the solitary tract. Important factor in both ventromedial hypothalamus neuronal sensing of long-chain fatty acid and the regulation of energy and glucose homeostasis. Receptor for thrombospondins, THBS1 and THBS2, mediating their antiangiogenic effects. Involved in inducing apoptosis in podocytes in response to elevated free fatty acids, acting together with THBS1. As a coreceptor for TLR4:TLR6 heterodimer, promotes inflammation in monocytes/macrophages. Upon ligand binding, such as oxLDL or amyloid-beta 42, interacts with the heterodimer TLR4:TLR6, the complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion, through the priming and activation of the NLRP3 inflammasome. Selective and nonredundant sensor of microbial diacylated lipopeptide that signal via TLR2:TLR6 heterodimer, this cluster triggers signaling from the cell surface, leading to the NF-kappa-B-dependent production of TNF, via MYD88 signaling pathway and subsequently is targeted to the Golgi in a lipid-raft dependent pathway ; (Microbial infection) Directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes and the internalization of particles independently of TLR signaling.
• KEGG Pathway:
  PPAR sig.ling pathway (hsa03320)
  Phagosome (hsa04145)
  Efferocytosis (hsa04148)
  AMPK sig.ling pathway (hsa04152)
  ECM-receptor interaction (hsa04512)
  Hematopoietic cell lineage (hsa04640)
  Adipocytokine sig.ling pathway (hsa04920)
  Insulin resistance (hsa04931)
  Fat digestion and absorption (hsa04975)
  Cholesterol metabolism (hsa04979)
  Malaria (hsa05144)
  Diabetic cardiomyopathy (hsa05415)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Cross-presentation of particulate exogenous antigens (phagosomes) (R-HSA-1236973)
  ER-Phagosome pathway (R-HSA-1236974)
  MyD88 (R-HSA-166058)
  Toll Like Receptor TLR6 (R-HSA-168188)
  PPARA activates gene expression (R-HSA-1989781)
  Scavenging by Class B Receptors (R-HSA-3000471)
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  Intracellular metabolism of fatty acids regulates insulin secretion (R-HSA-434313)
  MyD88 deficiency (TLR2/4) (R-HSA-5602498)
  IRAK4 deficiency (TLR2/4) (R-HSA-5603041)
  Regulation of TLR by endogenous ligand (R-HSA-5686938)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Neutrophil degranulation (R-HSA-6798695)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Platelet-type bleeding disorder 10	DISNNCXT	Strong	Autosomal recessive	[1]

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 Platelet glycoprotein 4 (CD36).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Platelet glycoprotein 4 (CD36).	[35]

59 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 Platelet glycoprotein 4 (CD36).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Platelet glycoprotein 4 (CD36).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Platelet glycoprotein 4 (CD36).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Platelet glycoprotein 4 (CD36).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Platelet glycoprotein 4 (CD36).	[7]
Triclosan	DMZUR4N	Approved	Triclosan affects the expression of Platelet glycoprotein 4 (CD36).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Platelet glycoprotein 4 (CD36).	[9]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Platelet glycoprotein 4 (CD36).	[10]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Platelet glycoprotein 4 (CD36).	[11]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Platelet glycoprotein 4 (CD36).	[12]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Platelet glycoprotein 4 (CD36).	[13]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Platelet glycoprotein 4 (CD36).	[14]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Platelet glycoprotein 4 (CD36).	[9]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Platelet glycoprotein 4 (CD36).	[15]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Platelet glycoprotein 4 (CD36).	[16]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Platelet glycoprotein 4 (CD36).	[17]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Platelet glycoprotein 4 (CD36).	[18]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Platelet glycoprotein 4 (CD36).	[19]
Bezafibrate	DMZDCS0	Approved	Bezafibrate increases the expression of Platelet glycoprotein 4 (CD36).	[20]
Vitamin B3	DMQVRZH	Approved	Vitamin B3 increases the expression of Platelet glycoprotein 4 (CD36).	[21]
Allopurinol	DMLPAOB	Approved	Allopurinol decreases the expression of Platelet glycoprotein 4 (CD36).	[9]
Tolcapone	DM8MNVO	Approved	Tolcapone increases the expression of Platelet glycoprotein 4 (CD36).	[22]
Candesartan	DMRK8OT	Approved	Candesartan increases the expression of Platelet glycoprotein 4 (CD36).	[23]
Asasantin	DMCZIHT	Approved	Asasantin decreases the expression of Platelet glycoprotein 4 (CD36).	[24]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Platelet glycoprotein 4 (CD36).	[25]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of Platelet glycoprotein 4 (CD36).	[26]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Platelet glycoprotein 4 (CD36).	[27]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Platelet glycoprotein 4 (CD36).	[28]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Platelet glycoprotein 4 (CD36).	[29]
Telmisartan	DMS3GX2	Phase 3 Trial	Telmisartan increases the expression of Platelet glycoprotein 4 (CD36).	[23]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone decreases the expression of Platelet glycoprotein 4 (CD36).	[30]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of Platelet glycoprotein 4 (CD36).	[31]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Platelet glycoprotein 4 (CD36).	[32]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate decreases the expression of Platelet glycoprotein 4 (CD36).	[18]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram decreases the expression of Platelet glycoprotein 4 (CD36).	[33]
Netoglitazone	DM8H7OA	Phase 2	Netoglitazone increases the expression of Platelet glycoprotein 4 (CD36).	[34]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Platelet glycoprotein 4 (CD36).	[36]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Platelet glycoprotein 4 (CD36).	[37]
Eugenol	DM7US1H	Patented	Eugenol decreases the expression of Platelet glycoprotein 4 (CD36).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Platelet glycoprotein 4 (CD36).	[38]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Platelet glycoprotein 4 (CD36).	[39]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Platelet glycoprotein 4 (CD36).	[8]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Platelet glycoprotein 4 (CD36).	[40]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug affects the expression of Platelet glycoprotein 4 (CD36).	[41]
U0126	DM31OGF	Investigative	U0126 increases the expression of Platelet glycoprotein 4 (CD36).	[32]
Oleic acid	DM54O1Z	Investigative	Oleic acid increases the expression of Platelet glycoprotein 4 (CD36).	[42]
PD98059	DMZC90M	Investigative	PD98059 increases the expression of Platelet glycoprotein 4 (CD36).	[32]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Platelet glycoprotein 4 (CD36).	[42]
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Investigative	15-deoxy-Delta(12, 14)-prostaglandin J(2) increases the expression of Platelet glycoprotein 4 (CD36).	[43]
27-hydroxycholesterol	DM2L6OZ	Investigative	27-hydroxycholesterol increases the expression of Platelet glycoprotein 4 (CD36).	[44]
Choline	DM5D9YK	Investigative	Choline affects the expression of Platelet glycoprotein 4 (CD36).	[45]
Hydroxydimethylarsine Oxide	DMPS2B1	Investigative	Hydroxydimethylarsine Oxide decreases the expression of Platelet glycoprotein 4 (CD36).	[46]
CITCO	DM0N634	Investigative	CITCO increases the expression of Platelet glycoprotein 4 (CD36).	[42]
Anandamide	DMCKH3P	Investigative	Anandamide increases the expression of Platelet glycoprotein 4 (CD36).	[47]
Erythropoietin	DM3R8YL	Investigative	Erythropoietin increases the expression of Platelet glycoprotein 4 (CD36).	[23]
24(S)-hydroxycholesterol	DMGMWA6	Investigative	24(S)-hydroxycholesterol increases the expression of Platelet glycoprotein 4 (CD36).	[44]
7alpha-hydroxycholesterol	DMH6LD0	Investigative	7alpha-hydroxycholesterol increases the expression of Platelet glycoprotein 4 (CD36).	[44]
24(S), 25-epoxycholesterol	DMW2KI5	Investigative	24(S), 25-epoxycholesterol decreases the expression of Platelet glycoprotein 4 (CD36).	[17]
arvanil	DMO5LUF	Investigative	arvanil increases the expression of Platelet glycoprotein 4 (CD36).	[47]

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