Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRU7THO)

• DOT Name: Bile salt export pump (ABCB11)
• Synonyms: EC 7.6.2.-; ATP-binding cassette sub-family B member 11
• Gene Name: ABCB11
• Related Disease:
  Progressive familial intrahepatic cholestasis type 2
  Benign recurrent intrahepatic cholestasis type 2
• UniProt ID: ABCBB_HUMAN
• PDB ID: 6LR0; 7DV5; 7E1A; 8PM6; 8PMD; 8PMJ
• EC Number: 7.6.2.-
• Pfam ID: PF00664 ; PF00005
• Sequence:
  MSDSVILRSIKKFGEENDGFESDKSYNNDKKSRLQDEKKGDGVRVGFFQLFRFSSSTDIW
  LMFVGSLCAFLHGIAQPGVLLIFGTMTDVFIDYDVELQELQIPGKACVNNTIVWTNSSLN
  QNMTNGTRCGLLNIESEMIKFASYYAGIAVAVLITGYIQICFWVIAAARQIQKMRKFYFR
  RIMRMEIGWFDCNSVGELNTRFSDDINKINDAIADQMALFIQRMTSTICGFLLGFFRGWK
  LTLVIISVSPLIGIGAATIGLSVSKFTDYELKAYAKAGVVADEVISSMRTVAAFGGEKRE
  VERYEKNLVFAQRWGIRKGIVMGFFTGFVWCLIFLCYALAFWYGSTLVLDEGEYTPGTLV
  QIFLSVIVGALNLGNASPCLEAFATGRAAATSIFETIDRKPIIDCMSEDGYKLDRIKGEI
  EFHNVTFHYPSRPEVKILNDLNMVIKPGEMTALVGPSGAGKSTALQLIQRFYDPCEGMVT
  VDGHDIRSLNIQWLRDQIGIVEQEPVLFSTTIAENIRYGREDATMEDIVQAAKEANAYNF
  IMDLPQQFDTLVGEGGGQMSGGQKQRVAIARALIRNPKILLLDMATSALDNESEAMVQEV
  LSKIQHGHTIISVAHRLSTVRAADTIIGFEHGTAVERGTHEELLERKGVYFTLVTLQSQG
  NQALNEEDIKDATEDDMLARTFSRGSYQDSLRASIRQRSKSQLSYLVHEPPLAVVDHKST
  YEEDRKDKDIPVQEEVEPAPVRRILKFSAPEWPYMLVGSVGAAVNGTVTPLYAFLFSQIL
  GTFSIPDKEEQRSQINGVCLLFVAMGCVSLFTQFLQGYAFAKSGELLTKRLRKFGFRAML
  GQDIAWFDDLRNSPGALTTRLATDASQVQGAAGSQIGMIVNSFTNVTVAMIIAFSFSWKL
  SLVILCFFPFLALSGATQTRMLTGFASRDKQALEMVGQITNEALSNIRTVAGIGKERRFI
  EALETELEKPFKTAIQKANIYGFCFAFAQCIMFIANSASYRYGGYLISNEGLHFSYVFRV
  ISAVVLSATALGRAFSYTPSYAKAKISAARFFQLLDRQPPISVYNTAGEKWDNFQGKIDF
  VDCKFTYPSRPDSQVLNGLSVSISPGQTLAFVGSSGCGKSTSIQLLERFYDPDQGKVMID
  GHDSKKVNVQFLRSNIGIVSQEPVLFACSIMDNIKYGDNTKEIPMERVIAAAKQAQLHDF
  VMSLPEKYETNVGSQGSQLSRGEKQRIAIARAIVRDPKILLLDEATSALDTESEKTVQVA
  LDKAREGRTCIVIAHRLSTIQNADIIAVMAQGVVIEKGTHEELMAQKGAYYKLVTTGSPI
  S
• Function: Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner. Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts. Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion.
• Tissue Specificity: Expressed predominantly, if not exclusively in the liver, where it was further localized to the canalicular microvilli and to subcanalicular vesicles of the hepatocytes by in situ.
• KEGG Pathway:
  Endocrine resistance (hsa01522)
  ABC transporters (hsa02010)
  Bile secretion (hsa04976)
  Cholesterol metabolism (hsa04979)
• Reactome Pathway:
  Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol (R-HSA-193368)
  Defective ABCB11 causes PFIC2 and BRIC2 (R-HSA-5678520)
  Recycling of bile acids and salts (R-HSA-159418)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Progressive familial intrahepatic cholestasis type 2	DISU4A6Q	Definitive	Autosomal recessive	[1]
Benign recurrent intrahepatic cholestasis type 2	DISCNRNR	Strong	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ginsenoside Re	DM46FVD	Investigative	Bile salt export pump (ABCB11) increases the transport of Ginsenoside Re.	[29]
Glycocholic acid	DM0SXNM	Investigative	Bile salt export pump (ABCB11) affects the transport of Glycocholic acid.	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Bile salt export pump (ABCB11).	[3]

99 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 Bile salt export pump (ABCB11).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Bile salt export pump (ABCB11).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Bile salt export pump (ABCB11).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Bile salt export pump (ABCB11).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Bile salt export pump (ABCB11).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Bile salt export pump (ABCB11).	[9]
Progesterone	DMUY35B	Approved	Progesterone decreases the activity of Bile salt export pump (ABCB11).	[10]
Menadione	DMSJDTY	Approved	Menadione decreases the expression of Bile salt export pump (ABCB11).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Bile salt export pump (ABCB11).	[11]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the activity of Bile salt export pump (ABCB11).	[12]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the activity of Bile salt export pump (ABCB11).	[10]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the activity of Bile salt export pump (ABCB11).	[13]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Bile salt export pump (ABCB11).	[14]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the activity of Bile salt export pump (ABCB11).	[13]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the activity of Bile salt export pump (ABCB11).	[10]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the activity of Bile salt export pump (ABCB11).	[15]
Clozapine	DMFC71L	Approved	Clozapine decreases the activity of Bile salt export pump (ABCB11).	[16]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the activity of Bile salt export pump (ABCB11).	[13]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Bile salt export pump (ABCB11).	[17]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the activity of Bile salt export pump (ABCB11).	[13]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Bile salt export pump (ABCB11).	[18]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the activity of Bile salt export pump (ABCB11).	[13]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Bile salt export pump (ABCB11).	[9]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the activity of Bile salt export pump (ABCB11).	[15]
Vinblastine	DM5TVS3	Approved	Vinblastine decreases the activity of Bile salt export pump (ABCB11).	[10]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the activity of Bile salt export pump (ABCB11).	[13]
Liothyronine	DM6IR3P	Approved	Liothyronine decreases the activity of Bile salt export pump (ABCB11).	[19]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the activity of Bile salt export pump (ABCB11).	[19]
Sorafenib	DMS8IFC	Approved	Sorafenib decreases the activity of Bile salt export pump (ABCB11).	[13]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid increases the expression of Bile salt export pump (ABCB11).	[20]
Gefitinib	DM15F0X	Approved	Gefitinib decreases the activity of Bile salt export pump (ABCB11).	[13]
Imatinib	DM7RJXL	Approved	Imatinib decreases the activity of Bile salt export pump (ABCB11).	[13]
Ritonavir	DMU764S	Approved	Ritonavir decreases the activity of Bile salt export pump (ABCB11).	[13]
Nefazodone	DM4ZS8M	Approved	Nefazodone decreases the activity of Bile salt export pump (ABCB11).	[21]
Chenodiol	DMQ8JIK	Approved	Chenodiol increases the expression of Bile salt export pump (ABCB11).	[22]
Bosentan	DMIOGBU	Approved	Bosentan decreases the expression of Bile salt export pump (ABCB11).	[23]
Lovastatin	DM9OZWQ	Approved	Lovastatin decreases the activity of Bile salt export pump (ABCB11).	[15]
Bezafibrate	DMZDCS0	Approved	Bezafibrate decreases the expression of Bile salt export pump (ABCB11).	[24]
Olanzapine	DMPFN6Y	Approved	Olanzapine decreases the activity of Bile salt export pump (ABCB11).	[16]
Deoxycholic acid	DM3GYAL	Approved	Deoxycholic acid increases the expression of Bile salt export pump (ABCB11).	[20]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus decreases the activity of Bile salt export pump (ABCB11).	[15]
Atazanavir	DMSYRBX	Approved	Atazanavir decreases the activity of Bile salt export pump (ABCB11).	[10]
Methimazole	DM25FL8	Approved	Methimazole increases the expression of Bile salt export pump (ABCB11).	[25]
Omeprazole	DM471KJ	Approved	Omeprazole decreases the activity of Bile salt export pump (ABCB11).	[13]
Clotrimazole	DMMFCIH	Approved	Clotrimazole decreases the activity of Bile salt export pump (ABCB11).	[10]
Nifedipine	DMSVOZT	Approved	Nifedipine decreases the activity of Bile salt export pump (ABCB11).	[10]
Clavulanate	DM2FGRT	Approved	Clavulanate decreases the expression of Bile salt export pump (ABCB11).	[7]
Lapatinib	DM3BH1Y	Approved	Lapatinib decreases the activity of Bile salt export pump (ABCB11).	[13]
Clofibrate	DMPC1J7	Approved	Clofibrate decreases the activity of Bile salt export pump (ABCB11).	[13]
Nelfinavir mesylate	DMFX6G8	Approved	Nelfinavir mesylate decreases the activity of Bile salt export pump (ABCB11).	[13]
Efavirenz	DMC0GSJ	Approved	Efavirenz decreases the activity of Bile salt export pump (ABCB11).	[10]
Naproxen	DMZ5RGV	Approved	Naproxen decreases the activity of Bile salt export pump (ABCB11).	[10]
Erythromycin	DM4K7GQ	Approved	Erythromycin decreases the activity of Bile salt export pump (ABCB11).	[10]
Budesonide	DMJIBAW	Approved	Budesonide decreases the activity of Bile salt export pump (ABCB11).	[10]
Atenolol	DMNKG1Z	Approved	Atenolol decreases the activity of Bile salt export pump (ABCB11).	[10]
Loratadine	DMF3AN7	Approved	Loratadine decreases the activity of Bile salt export pump (ABCB11).	[15]
Flucloxacillin	DMNUWST	Approved	Flucloxacillin decreases the activity of Bile salt export pump (ABCB11).	[10]
Reserpine	DM6VM38	Approved	Reserpine decreases the activity of Bile salt export pump (ABCB11).	[13]
Salbutamol	DMN9CWF	Approved	Salbutamol increases the expression of Bile salt export pump (ABCB11).	[26]
Tolcapone	DM8MNVO	Approved	Tolcapone decreases the activity of Bile salt export pump (ABCB11).	[13]
Benzbromarone	DMC3YUA	Approved	Benzbromarone decreases the activity of Bile salt export pump (ABCB11).	[13]
Spironolactone	DM2AQ5N	Approved	Spironolactone decreases the activity of Bile salt export pump (ABCB11).	[10]
Dobutamine	DMD1B8Z	Approved	Dobutamine decreases the activity of Bile salt export pump (ABCB11).	[19]
Zafirlukast	DMHNQOG	Approved	Zafirlukast decreases the activity of Bile salt export pump (ABCB11).	[15]
Cholic acid	DM7OKQV	Approved	Cholic acid increases the expression of Bile salt export pump (ABCB11).	[20]
Cetrorelix	DMFD9Q6	Approved	Cetrorelix decreases the activity of Bile salt export pump (ABCB11).	[15]
Felodipine	DMOSW35	Approved	Felodipine decreases the activity of Bile salt export pump (ABCB11).	[10]
Indinavir	DM0T3YH	Approved	Indinavir decreases the activity of Bile salt export pump (ABCB11).	[13]
Glibenclamide	DM8JXPZ	Approved	Glibenclamide decreases the activity of Bile salt export pump (ABCB11).	[27]
Primaquine	DMWQ16I	Approved	Primaquine decreases the activity of Bile salt export pump (ABCB11).	[13]
Dipyridamole	DMXY30O	Approved	Dipyridamole decreases the activity of Bile salt export pump (ABCB11).	[15]
Atropine	DMEN6X7	Approved	Atropine decreases the activity of Bile salt export pump (ABCB11).	[10]
Bromfenac	DMKB79O	Approved	Bromfenac decreases the activity of Bile salt export pump (ABCB11).	[16]
Ofloxacin	DM0VQN3	Approved	Ofloxacin decreases the activity of Bile salt export pump (ABCB11).	[10]
Clarithromycin	DM4M1SG	Approved	Clarithromycin decreases the activity of Bile salt export pump (ABCB11).	[10]
Lopinavir	DMITQS0	Approved	Lopinavir decreases the activity of Bile salt export pump (ABCB11).	[13]
Octreotide	DMHIDCJ	Approved	Octreotide decreases the activity of Bile salt export pump (ABCB11).	[15]
Glimepiride	DM5FSJA	Approved	Glimepiride decreases the activity of Bile salt export pump (ABCB11).	[13]
Ezetimibe	DM7A8TW	Approved	Ezetimibe decreases the activity of Bile salt export pump (ABCB11).	[10]
Pazopanib	DMF57DM	Approved	Pazopanib decreases the activity of Bile salt export pump (ABCB11).	[13]
Pitavastatin	DMJH792	Approved	Pitavastatin decreases the activity of Bile salt export pump (ABCB11).	[10]
Isradipine	DMA5XGH	Approved	Isradipine decreases the activity of Bile salt export pump (ABCB11).	[10]
Danazol	DML8KTN	Approved	Danazol decreases the activity of Bile salt export pump (ABCB11).	[15]
Norethindrone	DMTY169	Approved	Norethindrone decreases the activity of Bile salt export pump (ABCB11).	[13]
Primidone	DM0WX6I	Approved	Primidone decreases the activity of Bile salt export pump (ABCB11).	[19]
Dehydroepiandrosterone sulfate	DM4Q80H	Approved	Dehydroepiandrosterone sulfate decreases the activity of Bile salt export pump (ABCB11).	[10]
Itraconazole	DMCR1MV	Approved	Itraconazole decreases the activity of Bile salt export pump (ABCB11).	[13]
Saquinavir	DMG814N	Approved	Saquinavir decreases the activity of Bile salt export pump (ABCB11).	[13]
Luvox	DMJKROX	Approved	Luvox decreases the activity of Bile salt export pump (ABCB11).	[10]
Midazolam	DMXOELT	Approved	Midazolam decreases the activity of Bile salt export pump (ABCB11).	[13]
Pimecrolimus	DMZLGRB	Approved	Pimecrolimus decreases the activity of Bile salt export pump (ABCB11).	[15]
Sulfamethoxazole	DMB08GE	Approved	Sulfamethoxazole decreases the activity of Bile salt export pump (ABCB11).	[10]
Nitrofurantoin	DM7PQIK	Approved	Nitrofurantoin decreases the activity of Bile salt export pump (ABCB11).	[10]
Sulfinpyrazone	DMEV954	Approved	Sulfinpyrazone decreases the activity of Bile salt export pump (ABCB11).	[10]
Tolvaptan	DMIWFRL	Approved	Tolvaptan decreases the activity of Bile salt export pump (ABCB11).	[28]
Amprenavir	DMLMXE0	Approved	Amprenavir decreases the activity of Bile salt export pump (ABCB11).	[13]
Cisapride	DMY7PED	Approved	Cisapride decreases the activity of Bile salt export pump (ABCB11).	[15]
Nitrendipine	DM21C09	Approved	Nitrendipine decreases the activity of Bile salt export pump (ABCB11).	[13]
Repaglinide	DM5SXUV	Approved	Repaglinide decreases the activity of Bile salt export pump (ABCB11).	[15]

References

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• [2] Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):2011-6. doi: 10.1073/pnas.98.4.2011. Epub 2001 Feb 6.
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