Details of Drug Off-Target (DOT)

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

• DOT Name: NPC intracellular cholesterol transporter 1 (NPC1)
• Synonyms: Niemann-Pick C1 protein
• Gene Name: NPC1
• Related Disease:
  Niemann-Pick disease, type C1
  Pulmonary disease
  Advanced cancer
  Alzheimer disease
  Atherosclerosis
  Brucellosis
  Burkitt lymphoma
  Carcinoma
  Cardiovascular disease
  Cerebellar ataxia
  Coronary atherosclerosis
  Coronary heart disease
  Crohn disease
  Dementia
  Depression
  Epithelial neoplasm
  Fatty liver disease
  Gastric cancer
  Gastrointestinal stromal tumour
  Hepatitis B virus infection
  Liver cirrhosis
  Lung cancer
  Lung carcinoma
  Lysosomal storage disease
  Metastatic malignant neoplasm
  Nervous system disease
  Niemann-pick disease
  Niemann-Pick disease, type C2
  Non-insulin dependent diabetes
  Pancreatic cancer
  Plasma cell myeloma
  Progressive supranuclear palsy
  Schizophrenia
  Sensory ataxia
  Stomach cancer
  Tauopathy
  Colorectal carcinoma
  High blood pressure
  Lysosomal lipid storage disorder
  Movement disorder
  Stroke
  Niemann-Pick disease type C, adult neurologic onset
  Niemann-Pick disease type C, juvenile neurologic onset
  Niemann-Pick disease type C, late infantile neurologic onset
  Niemann-Pick disease type C, severe early infantile neurologic onset
  Niemann-Pick disease type C, severe perinatal form
  Adenocarcinoma
  Anxiety
  Anxiety disorder
  Ebola virus infection
  Epstein barr virus infection
  Hepatitis C virus infection
  Neuroblastoma
  Obesity
• UniProt ID: NPC1_HUMAN
• PDB ID: 3GKH; 3GKI; 3GKJ; 3JD8; 5F18; 5F1B; 5HNS; 5JNX; 5KWY; 5U73; 5U74; 6UOX; 6W5R; 6W5S; 6W5T; 6W5U; 6W5V; 8EUS
• Pfam ID: PF16414 ; PF02460 ; PF12349
• Sequence:
  MTARGLALGLLLLLLCPAQVFSQSCVWYGECGIAYGDKRYNCEYSGPPKPLPKDGYDLVQ
  ELCPGFFFGNVSLCCDVRQLQTLKDNLQLPLQFLSRCPSCFYNLLNLFCELTCSPRQSQF
  LNVTATEDYVDPVTNQTKTNVKELQYYVGQSFANAMYNACRDVEAPSSNDKALGLLCGKD
  ADACNATNWIEYMFNKDNGQAPFTITPVFSDFPVHGMEPMNNATKGCDESVDEVTAPCSC
  QDCSIVCGPKPQPPPPPAPWTILGLDAMYVIMWITYMAFLLVFFGAFFAVWCYRKRYFVS
  EYTPIDSNIAFSVNASDKGEASCCDPVSAAFEGCLRRLFTRWGSFCVRNPGCVIFFSLVF
  ITACSSGLVFVRVTTNPVDLWSAPSSQARLEKEYFDQHFGPFFRTEQLIIRAPLTDKHIY
  QPYPSGADVPFGPPLDIQILHQVLDLQIAIENITASYDNETVTLQDICLAPLSPYNTNCT
  ILSVLNYFQNSHSVLDHKKGDDFFVYADYHTHFLYCVRAPASLNDTSLLHDPCLGTFGGP
  VFPWLVLGGYDDQNYNNATALVITFPVNNYYNDTEKLQRAQAWEKEFINFVKNYKNPNLT
  ISFTAERSIEDELNRESDSDVFTVVISYAIMFLYISLALGHMKSCRRLLVDSKVSLGIAG
  ILIVLSSVACSLGVFSYIGLPLTLIVIEVIPFLVLAVGVDNIFILVQAYQRDERLQGETL
  DQQLGRVLGEVAPSMFLSSFSETVAFFLGALSVMPAVHTFSLFAGLAVFIDFLLQITCFV
  SLLGLDIKRQEKNRLDIFCCVRGAEDGTSVQASESCLFRFFKNSYSPLLLKDWMRPIVIA
  IFVGVLSFSIAVLNKVDIGLDQSLSMPDDSYMVDYFKSISQYLHAGPPVYFVLEEGHDYT
  SSKGQNMVCGGMGCNNDSLVQQIFNAAQLDNYTRIGFAPSSWIDDYFDWVKPQSSCCRVD
  NITDQFCNASVVDPACVRCRPLTPEGKQRPQGGDFMRFLPMFLSDNPNPKCGKGGHAAYS
  SAVNILLGHGTRVGATYFMTYHTVLQTSADFIDALKKARLIASNVTETMGINGSAYRVFP
  YSVFYVFYEQYLTIIDDTIFNLGVSLGAIFLVTMVLLGCELWSAVIMCATIAMVLVNMFG
  VMWLWGISLNAVSLVNLVMSCGISVEFCSHITRAFTVSMKGSRVERAEEALAHMGSSVFS
  GITLTKFGGIVVLAFAKSQIFQIFYFRMYLAMVLLGATHGLIFLPVLLSYIGPSVNKAKS
  CATEERYKGTERERLLNF
• Function: Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment. Unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes is transferred by NPC2 to the cholesterol-binding pocket in the N-terminal domain of NPC1. Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket. Binds oxysterol with higher affinity than cholesterol. May play a role in vesicular trafficking in glia, a process that may be crucial for maintaining the structural and functional integrity of nerve terminals (Probable). Inhibits cholesterol-mediated mTORC1 activation throught its interaction with SLC38A9 ; (Microbial infection) Acts as an endosomal entry receptor for ebolavirus.
• KEGG Pathway:
  Virion - Ebolavirus and Lyssavirus (hsa03265)
  Lysosome (hsa04142)
  Cholesterol metabolism (hsa04979)
• Reactome Pathway: LDL clearance (R-HSA-8964038)

Molecular Interaction Atlas (MIA) of This DOT

54 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Niemann-Pick disease, type C1	DIS9HUE3	Definitive	Autosomal recessive	[1]
Pulmonary disease	DIS6060I	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[4]
Atherosclerosis	DISMN9J3	Strong	Therapeutic	[5]
Brucellosis	DISEAYGH	Strong	Biomarker	[6]
Burkitt lymphoma	DIS9D5XU	Strong	Genetic Variation	[7]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[8]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[9]
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[10]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[11]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[12]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[13]
Dementia	DISXL1WY	Strong	Genetic Variation	[14]
Depression	DIS3XJ69	Strong	Altered Expression	[15]
Epithelial neoplasm	DIS0T594	Strong	Biomarker	[16]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[17]
Gastric cancer	DISXGOUK	Strong	Biomarker	[18]
Gastrointestinal stromal tumour	DIS6TJYS	Strong	Biomarker	[19]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[20]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[21]
Lung cancer	DISCM4YA	Strong	Biomarker	[18]
Lung carcinoma	DISTR26C	Strong	Biomarker	[22]
Lysosomal storage disease	DIS6QM6U	Strong	Biomarker	[23]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[24]
Nervous system disease	DISJ7GGT	Strong	Genetic Variation	[25]
Niemann-pick disease	DISKS5FO	Strong	Biomarker	[26]
Niemann-Pick disease, type C2	DISLYVZZ	Strong	Biomarker	[27]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[28]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[29]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[30]
Progressive supranuclear palsy	DISO5KRQ	Strong	Biomarker	[31]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[32]
Sensory ataxia	DISSMCYQ	Strong	Biomarker	[33]
Stomach cancer	DISKIJSX	Strong	Biomarker	[18]
Tauopathy	DISY2IPA	Strong	Biomarker	[34]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[35]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[36]
Lysosomal lipid storage disorder	DISXQRTX	moderate	Genetic Variation	[37]
Movement disorder	DISOJJ2D	moderate	Genetic Variation	[38]
Stroke	DISX6UHX	moderate	Biomarker	[39]
Niemann-Pick disease type C, adult neurologic onset	DISVQ9PR	Supportive	Autosomal recessive	[40]
Niemann-Pick disease type C, juvenile neurologic onset	DISBAITH	Supportive	Autosomal recessive	[40]
Niemann-Pick disease type C, late infantile neurologic onset	DISOO4DE	Supportive	Autosomal recessive	[40]
Niemann-Pick disease type C, severe early infantile neurologic onset	DISK3V8S	Supportive	Autosomal recessive	[40]
Niemann-Pick disease type C, severe perinatal form	DISOIE66	Supportive	Autosomal recessive	[40]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[41]
Anxiety	DISIJDBA	Limited	Biomarker	[42]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[42]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[43]
Epstein barr virus infection	DISOO0WT	Limited	Genetic Variation	[44]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[45]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[46]
Obesity	DIS47Y1K	Limited	Biomarker	[28]

This DOT Affected the Regulation of Drug Effects of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Daunorubicin	DMQUSBT	Approved	NPC intracellular cholesterol transporter 1 (NPC1) increases the secretion of Daunorubicin.	[70]
ANW-32821	DMMJOZD	Phase 2	NPC intracellular cholesterol transporter 1 (NPC1) increases the secretion of ANW-32821.	[70]

23 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 NPC intracellular cholesterol transporter 1 (NPC1).	[47]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[48]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[49]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[50]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[51]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[52]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[53]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[54]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[55]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[56]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[57]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[58]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[59]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[60]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[61]
GSK618334	DMJPXZ4	Phase 1	GSK618334 increases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[62]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[63]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[64]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[65]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[66]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[67]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[68]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 increases the expression of NPC intracellular cholesterol transporter 1 (NPC1).	[69]

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