Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DT3D8F0)

• DTP Name: Organic anion transporting polypeptide 1B1 (SLCO1B1)
• Gene Name: SLCO1B1
• UniProt ID: Q9Y6L6 (SO1B1_HUMAN)
• VARIDT ID: DTD0008
• Synonyms: LST-1; LST1; Liver-specific organic anion transporter 1; OATP-2; OATP-C; OATP1B1; OATP2; OATPC; SLC21A6; SLCO1B1; Sodium-independent organic anion-transporting polypeptide 2; Solute carrier family 21 member 6; Solute carrier organic anion transporter family member 1B1
• DTP Family: Organo Anion Transporter (OAT) Family
• Tissue Specificity: High expressed in sinusoidal (basolateral) membrane of hepatocytes, and is expressed uniformly throughout the lobules
• Sequence:
  MDQNQHLNKTAEAQPSENKKTRYCNGLKMFLAALSLSFIAKTLGAIIMKSSIIHIERRFE
  ISSSLVGFIDGSFEIGNLLVIVFVSYFGSKLHRPKLIGIGCFIMGIGGVLTALPHFFMGY
  YRYSKETNINSSENSTSTLSTCLINQILSLNRASPEIVGKGCLKESGSYMWIYVFMGNML
  RGIGETPIVPLGLSYIDDFAKEGHSSLYLGILNAIAMIGPIIGFTLGSLFSKMYVDIGYV
  DLSTIRITPTDSRWVGAWWLNFLVSGLFSIISSIPFFFLPQTPNKPQKERKASLSLHVLE
  TNDEKDQTANLTNQGKNITKNVTGFFQSFKSILTNPLYVMFVLLTLLQVSSYIGAFTYVF
  KYVEQQYGQPSSKANILLGVITIPIFASGMFLGGYIIKKFKLNTVGIAKFSCFTAVMSLS
  FYLLYFFILCENKSVAGLTMTYDGNNPVTSHRDVPLSYCNSDCNCDESQWEPVCGNNGIT
  YISPCLAGCKSSSGNKKPIVFYNCSCLEVTGLQNRNYSAHLGECPRDDACTRKFYFFVAI
  QVLNLFFSALGGTSHVMLIVKIVQPELKSLALGFHSMVIRALGGILAPIYFGALIDTTCI
  KWSTNNCGTRGSCRTYNSTSFSRVYLGLSSMLRVSSLVLYIILIYAMKKKYQEKDINASE
  NGSVMDEANLESLNKNKHFVPSAGADSETHC
• Function: This transporter involved in the clearance of bile acids and organic anions from the liver. Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine.
• Endogenous Substrate(s): Bisglucuronosyl bilirubin; Cholate; Dehydroepiandrosterone sulfate; Eicosanoids; Monoglucuronosyl bilirubin; Thyroid hormones; Tauroursodeoxycholate
• TCDB ID: 2.A.60.1.5
• Gene ID: 10599
• KEGG Pathway: Bile secretion (hsa04976)
• Reactome Pathway:
  Heme degradation (R-HSA-189483)
  Defective SLCO1B1 causes hyperbilirubinemia, Rotor type (HBLRR) (R-HSA-5619110)
  Transport of organic anions (R-HSA-879518)
  Atorvastatin ADME (R-HSA-9754706)
  Recycling of bile acids and salts (R-HSA-159418)

Molecular Interaction Atlas (MIA) of This DTP

64 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acocantherin	DM7JT24	Atrial fibrillation	BC81.3	Approved	[2]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[3]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[4]
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[5]
Bromfenac	DMKB79O	Pain	MG30-MG3Z	Approved	[6]
Caspofungin	DMGQIPT	Candidiasis	1F23	Approved	[7]
Cefazolin	DMPDYFR	Bacteremia	1A73	Approved	[7]
Cefditoren	DMSUVM1	Bacterial infection	1A00-1C4Z	Approved	[7]
Cefoperazone	DM53PV8	Bacterial infection	1A00-1C4Z	Approved	[7]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[8]
Cholic Acid	DM7OKQV	Cholelithiasis	DC11	Approved	[7]
Cilostazol	DMZMSCT	Intermittent claudication	BD40.00	Approved	[9]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[10]
Darunavir	DMN3GCH	Human immunodeficiency virus infection	1C62	Approved	[7]
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[10]
Dehydroepiandrosterone sulfate	DM4Q80H	N. A.	N. A.	Approved	[7]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[7]
Docetaxel	DMDI269	Advanced cancer	2A00-2F9Z	Approved	[8]
Eluxadoline	DMYZ0P1	Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[11]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[12]
Entacapone	DMLBVKQ	Parkinson disease	8A00.0	Approved	[6]
Estrone sulfate	DMVBIZL	Atrophic vaginitis	GA30.2	Approved	[13]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[14]
Ezetimibe	DM7A8TW	Atherosclerosis	BD40	Approved	[15]
FLUORESCEIN	DMQTFAO	Ocular disease	1F00.1Z	Approved	[6]
Fluvastatin	DM4MDJY	Arteriosclerosis	BD40	Approved	[16]
Gadobenate Dimeglumine	DM4VAOG	Schizophrenia	6A20	Approved	[17]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[10]
Hydroxyurea	DMOQVU9	Chronic myelogenous leukaemia	2A20.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[10]
Levothyroxine	DMHN027	Congenital hypothyroidism		Approved	[19]
Liothyronine	DM6IR3P	Congenital hypothyroidism		Approved	[19]
Lopinavir	DMITQS0	Human immunodeficiency virus infection	1C62	Approved	[7]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[20]
Mesalazine	DMOL5IU	Diverticulitis		Approved	[21]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[22]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[23]
Nafcillin	DMN9RPO	Arthritis	FA20	Approved	[7]
Nateglinide	DMLK2QH	Diabetic complication	5A2Y	Approved	[6]
Nilotinib	DM7HXWT	Chronic myelogenous leukaemia	2A20.0	Approved	[10]
Olmesartan medoxomil	DMWBHRY	High blood pressure	BA00	Approved	[24]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[25]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[7]
Pitavastatin	DMJH792	Hypercholesterolaemia	5C80.0	Approved	[26]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[27]
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[27]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[28]
Repaglinide	DM5SXUV	Diabetic complication	5A2Y	Approved	[29]
Rifampin	DMA8J1G	Tuberculosis	1B10-1B1Z	Approved	[30]
Rosuvastatin	DMMIQ7G	Arteriosclerosis	BD40	Approved	[31]
Saquinavir	DMG814N	Human immunodeficiency virus infection	1C62	Approved	[7]
Simeprevir	DMLUA9D	Chronic HCV-1 infection	1E51.1	Approved	[32]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[33]
Sirolimus	DMGW1ID	Advanced cancer	2A00-2F9Z	Approved	[34]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[10]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[10]
Technetium (99MTC) mebrofenin	DMUEWM3	N. A.	N. A.	Approved	[29]
Temocapril	DM1A79H	N. A.	N. A.	Approved	[7]
Torasemide	DMXKJ6C	Congestive heart failure	BD10	Approved	[35]
Ursodeoxycholic acid	DMCUT21	Cholelithiasis	DC11	Approved	[36]
Valsartan	DMREUQ6	Chronic heart failure	BD1Z	Approved	[2]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[10]
Vemurafenib	DM62UG5	Melanoma	2C30	Approved	[10]
Primovist	DM37FKA	N. A.	N. A.	Phase 4	[7]

12 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Atrasentan	DMM74PK	Diabetic nephropathy	GB61.Z	Phase 3	[7]
Benzylpenicillin	DMS9503	Actinomycosis		Phase 3	[7]
Karenitecin	DMCRGY4	Lung cancer	2C25.0	Phase 3	[7]
BQ-123	DM0MO8I	Pulmonary arterial hypertension	BB01.0	Phase 2	[7]
Cholyl lysyl fluorescein	DMALN2M	N. A.	N. A.	Phase 2	[7]
Danoprevir	DM20MDU	Hepatitis C virus infection	1E51.1	Phase 2	[8]
Flavopiridol	DMKSUOI	Acute myeloid leukaemia	2A60	Phase 2	[7]
Gimatecan	DMSKMET	Breast cancer	2C60-2C65	Phase 2	[7]
LE-SN38	DMW50NF	Colorectal cancer	2B91.Z	Phase 2	[7]
YM-758	DMU79X2	Angina pectoris	BA40	Phase 2	[7]
Sodium taurocholate	DM3GO0J	Type-2 diabetes	5A11	Phase 1/2	[2]
Taurocholic Acid	DM2LZ8F	Type-2 diabetes	5A11	Phase 1/2	[19]

1 Discontinued Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TR-14035	DMWD39E	Multiple sclerosis	8A40	Discontinued in Phase 1	[37]

8 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
bilirubin	DMI0V4O	Discovery agent	N.A.	Investigative	[38]
bromsulphthalein	DM9W2ZV	N. A.	N. A.	Investigative	[39]
CCK-8	DMN0J4W	N. A.	N. A.	Investigative	[7]
DADLE	DMRM0OW	Discovery agent	N.A.	Investigative	[7]
Fluo-3	DMLO9FU	N. A.	N. A.	Investigative	[40]
glycocholic acid	DM0SXNM	Discovery agent	N.A.	Investigative	[7]
LTE4	DMCPB0Q	Discovery agent	N.A.	Investigative	[7]
[3H]estradiol-17beta-glucuronide	DM3KJ45	Discovery agent	N.A.	Investigative	[41]

Molecular Expression Atlas (MEA) of This DTP

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	9.49E-02	5.87E-03	5.86E-02
Adrenocortical carcinoma	2D11.Z	Kidney	2.07E-01	3.07E-02	2.01E-01
Alopecia	ED70	Skin from scalp	2.75E-01	2.07E-02	9.26E-02
Alzheimer's disease	8A20	Entorhinal cortex	8.15E-01	6.20E-03	5.61E-02
Ankylosing spondylitis	FA92.0	Pheripheral blood	9.87E-01	1.11E-02	1.24E-01
Aortic stenosis	BB70	Calcified aortic valve	6.85E-01	-5.08E-02	-1.72E-01
Apnea	7A40	Hyperplastic tonsil	4.99E-01	-2.54E-04	-2.46E-03
Arthropathy	FA00-FA5Z	Peripheral blood	6.69E-01	4.88E-03	3.78E-02
Asthma	CA23	Nasal and bronchial airway	4.30E-05	7.91E-02	3.70E-01
Atopic dermatitis	EA80	Skin	3.30E-02	4.23E-02	2.51E-01
Autism	6A02	Whole blood	5.07E-01	-5.21E-02	-2.97E-01
Autoimmune uveitis	9A96	Peripheral monocyte	2.63E-01	-5.35E-02	-3.52E-01
Autosomal dominant monocytopenia	4B04	Whole blood	1.60E-02	-1.16E-01	-1.37E+00
Bacterial infection of gingival	1C1H	Gingival tissue	1.58E-03	4.02E-02	2.15E-01
Batten disease	5C56.1	Whole blood	7.27E-01	-9.38E-02	-1.09E+00
Behcet's disease	4A62	Peripheral blood	1.09E-01	-3.03E-02	-1.51E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	3.89E-01	-1.75E-02	-1.15E-01
Bladder cancer	2C94	Bladder tissue	1.23E-02	1.36E-02	1.01E-01
Breast cancer	2C60-2C6Z	Breast tissue	9.12E-01	9.67E-03	3.43E-02
Cardioembolic stroke	8B11.20	Whole blood	6.46E-01	-7.72E-02	-3.41E-01
Cervical cancer	2C77	Cervical tissue	1.35E-02	-9.49E-02	-4.27E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	9.37E-01	2.74E-02	1.51E-01
Chronic hepatitis C	1E51.1	Whole blood	4.29E-01	-1.04E-03	-1.20E-02
Chronic obstructive pulmonary disease	CA22	Lung tissue	2.41E-01	-2.63E-02	-8.50E-02
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	5.54E-01	-1.65E-02	-1.24E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	7.69E-01	1.88E-02	2.46E-01
Colon cancer	2B90	Colon tissue	3.12E-09	7.77E-02	3.84E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	3.17E-01	6.66E-02	4.62E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	2.93E-01	-1.09E-01	-3.82E-01
Endometriosis	GA10	Endometrium tissue	5.94E-01	-5.43E-03	-2.82E-02
Familial hypercholesterolemia	5C80.00	Peripheral blood	3.75E-01	6.66E-02	5.58E-01
Familial hypercholesterolemia	5C80.00	Whole blood	3.27E-01	-5.78E-02	-3.84E-01
Gastric cancer	2B72	Gastric tissue	9.20E-01	-1.59E-03	-9.27E-03
Glioblastopma	2A00.00	Nervous tissue	1.28E-02	-3.03E-02	-1.77E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	1.27E-01	-1.70E-01	-5.42E-01
Head and neck cancer	2D42	Head and neck tissue	8.73E-01	1.50E-03	9.14E-03
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	2.68E-01	-3.85E-02	-3.86E-01
Huntington's disease	8A01.10	Whole blood	2.23E-01	-6.79E-02	-4.89E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	6.11E-01	-1.87E-01	-9.80E-01
Immunodeficiency	4A00-4A20	Peripheral blood	2.21E-01	-5.57E-02	-6.30E-01
Influenza	1.00E+30	Whole blood	1.58E-01	1.80E-01	1.63E+00
Interstitial cystitis	GC00.3	Bladder tissue	1.67E-02	7.40E-02	1.58E+00
Intracranial aneurysm	8B01.0	Intracranial artery	5.08E-01	-9.92E-02	-5.05E-01
Irritable bowel syndrome	DD91.0	Rectal colon tissue	7.76E-01	-8.58E-03	-4.87E-02
Ischemic stroke	8B11	Peripheral blood	8.66E-01	1.67E-02	1.04E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	3.41E-01	9.35E-02	3.49E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	7.81E-01	-1.08E-01	-5.41E-01
Lateral sclerosis	8B60.4	Skin	5.23E-01	-1.00E-01	-3.26E-01
Liver cancer	2C12.0	Liver tissue	1.45E-26	-1.31E+00	-2.12E+00
Liver failure	DB99.7-DB99.8	Liver tissue	1.73E-03	-4.33E+00	-7.79E+00
Lung cancer	2C25	Lung tissue	2.80E-34	1.44E-01	9.71E-01
Lupus erythematosus	4A40	Whole blood	3.56E-04	5.83E-02	1.92E-01
Major depressive disorder	6A70-6A7Z	Whole blood	2.86E-01	9.09E-03	4.61E-02
Major depressive disorder	6A70-6A7Z	Hippocampus	8.47E-01	1.14E-02	8.20E-02
Melanoma	2C30	Skin	1.12E-01	-7.30E-02	-1.37E-01
Multiple myeloma	2A83.1	Bone marrow	1.50E-04	1.94E-01	2.06E+00
Multiple myeloma	2A83.1	Peripheral blood	6.86E-01	3.72E-02	2.86E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	3.23E-01	6.36E-02	5.84E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	9.55E-01	1.20E-02	9.21E-02
Myelofibrosis	2A20.2	Whole blood	3.14E-04	9.49E-02	8.25E-01
Myocardial infarction	BA41-BA50	Peripheral blood	1.73E-02	1.07E-01	2.61E-01
Myopathy	8C70.6	Muscle tissue	4.62E-01	-8.97E-03	-6.28E-02
Neonatal sepsis	KA60	Whole blood	2.70E-01	-2.71E-02	-1.46E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	6.37E-01	-1.96E-03	-1.14E-02
Non-alcoholic fatty liver disease	DB92	Liver tissue	2.00E-02	7.38E-01	9.90E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	5.57E-01	1.53E-02	1.76E-01
Olive pollen allergy	CA08.00	Peripheral blood	1.25E-01	-8.96E-02	-5.03E-01
Oral cancer	2B6E	Oral tissue	2.47E-04	1.32E-01	7.89E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	9.30E-01	7.68E-02	3.82E-01
Osteoporosis	FB83.1	Bone marrow	7.68E-02	1.80E-01	1.25E+00
Ovarian cancer	2C73	Ovarian tissue	5.40E-01	-3.16E-02	-1.22E-01
Pancreatic cancer	2C10	Pancreas	9.07E-02	-9.94E-02	-5.12E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	8.03E-01	8.37E-02	4.07E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	2.07E-01	5.26E-02	4.81E-01
Pituitary cancer	2D12	Pituitary tissue	1.88E-02	1.77E-01	9.29E-01
Pituitary gonadotrope tumour	2D12	Pituitary tissue	6.46E-02	2.08E-01	1.09E+00
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	3.33E-01	-5.25E-03	-4.09E-02
Polycythemia vera	2A20.4	Whole blood	3.85E-09	1.32E-01	1.12E+00
Pompe disease	5C51.3	Biceps muscle	1.38E-01	-1.46E-01	-1.22E+00
Preterm birth	KA21.4Z	Myometrium	7.18E-01	-5.08E-02	-4.53E-01
Prostate cancer	2C82	Prostate	7.59E-01	-3.08E-02	-1.64E-01
Psoriasis	EA90	Skin	3.65E-04	-1.54E-01	-7.81E-01
Rectal cancer	2B92	Rectal colon tissue	2.48E-01	-8.99E-02	-4.81E-01
Renal cancer	2C90-2C91	Kidney	6.76E-03	8.67E-02	6.17E-01
Retinoblastoma	2D02.2	Uvea	3.26E-02	1.34E-01	1.81E+00
Rheumatoid arthritis	FA20	Synovial tissue	5.71E-01	-1.33E-02	-6.44E-02
Rhinovirus infection	CA42.1	Nasal epithelium tissue	3.13E-01	3.50E-03	3.41E-02
Schizophrenia	6A20	Prefrontal cortex	9.01E-01	3.70E-03	2.13E-02
Schizophrenia	6A20	Superior temporal cortex	9.70E-01	2.57E-03	2.16E-02
Scleroderma	4A42.Z	Whole blood	1.26E-03	2.42E-01	1.68E+00
Seizure	8A60-8A6Z	Whole blood	4.28E-01	-5.35E-02	-3.18E-01
Sensitive skin	EK0Z	Skin	4.49E-01	-1.07E-01	-8.21E-01
Sepsis with septic shock	1G41	Whole blood	2.45E-01	3.59E-02	1.70E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	5.08E-01	-2.87E-02	-2.90E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	1.90E-01	8.99E-03	9.09E-02
Simpson golabi behmel syndrome	LD2C	Adipose tissue	9.30E-01	6.08E-02	3.23E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	1.00E-01	-3.29E-01	-1.92E+00
Skin cancer	2C30-2C3Z	Skin	2.65E-04	5.83E-02	1.94E-01
Thrombocythemia	3B63	Whole blood	2.66E-02	2.54E-02	2.28E-01
Thrombocytopenia	3B64	Whole blood	9.08E-02	1.19E-01	5.19E-01
Thyroid cancer	2D10	Thyroid	5.98E-03	9.85E-03	5.46E-02
Tibial muscular dystrophy	8C75	Muscle tissue	1.37E-01	-9.96E-02	-4.51E-01
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	2.24E-01	5.34E-02	6.68E-01
Type 2 diabetes	5A11	Liver tissue	2.81E-01	3.67E-02	2.82E-01
Ureter cancer	2C92	Urothelium	9.93E-01	-8.70E-02	-4.54E-01
Uterine cancer	2C78	Endometrium tissue	1.12E-01	8.17E-03	5.03E-02
Vitiligo	ED63.0	Skin	5.69E-01	-2.82E-02	-1.27E-01

Drug Affinity of This DTP Assessed by Cell Line

Approved Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
Atorvastatin	Approved	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 0.77 microM	[42]
Atorvastatin	Approved	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 12.4 microM	[43]
Atorvastatin	Approved	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 18.9 microM	[44]
Bosentan	Approved	Chinese hamster ovary (CHO) cells-OATP1B1	Km = 44.0 microM	[5]
Cilostazol	Approved	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 17.7 microM	[9]
Fluvastatin	Approved	Chinese hamster ovary (CHO) cells-OATP1B1	Km = 1.4 microM	[45]
Fluvastatin	Approved	Chinese hamster ovary (CHO) cells-OATP1B1	Km = 3.5 microM	[45]
Fluvastatin	Approved	Oocytes-OATP1B1	Km = 31.1 microM	[27]
Levothyroxine	Approved	Oocytes-OATP1B1	Km = 3.0 microM	[19]
Liothyronine	Approved	Oocytes-OATP1B1	Km = 2.7 microM	[19]
Mesalazine	Approved	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 55.1 microM	[21]
Olmesartan medoxomil	Approved	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 12.8 microM	[46]
Olmesartan medoxomil	Approved	Oocytes-OATP1B1	Km = 42.6 microM	[24]
PITAVASTATIN CALCIUM	Approved	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 3.0 microM	[47]
PITAVASTATIN CALCIUM	Approved	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 4.8 microM	[48]
PITAVASTATIN CALCIUM	Approved	Oocytes-OATP1B1	Km = 3.6 microM	[49]
PITAVASTATIN CALCIUM	Approved	Oocytes-OATP1B1	Km = 6.7 microM	[27]
Pravastatin	Approved	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 33.7 microM	[20]
Pravastatin	Approved	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 85.7 microM	[43]
Pravastatin	Approved	Oocytes-OATP1B1	Km = 57.5 microM	[27]
Rifampin	Approved	Human cervical cancer cell line (Hela)-OATP1B1	Km = 1.5 microM	[30]
Rifampin	Approved	Oocytes-OATP1B1	Km = 13.0 microM	[50]
Rosuvastatin	Approved	Human cervical cancer cell line (Hela)-OATP1B1	Km = 4.0 microM	[51]
Rosuvastatin	Approved	Human cervical cancer cell line (Hela)-OATP1B1	Km = 7.3 microM	[51]
Rosuvastatin	Approved	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 0.8 microM	[31]
Rosuvastatin	Approved	Oocytes-OATP1B1	Km = 8.5 microM	[52]
Valsartan	Approved	Chinese hamster ovary (CHO) cells-OATP1B1	Km = 17.8 microM	[53]
Valsartan	Approved	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 1.39 microM	[54]

Clinical Trial Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
Taurocholic Acid	Phase 1/2	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 33.8 microM	[20]
Taurocholic Acid	Phase 1/2	Oocytes-OATP1B1	Km = 13.6 microM	[19]

Investigative Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
bilirubin	Investigative	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 0.1 microM	[55]
bilirubin	Investigative	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 0.28 microM	[55]
bilirubin	Investigative	Oocytes-OATP1B1	Km = 0.0076 microM	[38]
bromsulphthalein	Investigative	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 0.14 microM	[55]
bromsulphthalein	Investigative	Oocytes-OATP1B1	Km = 0.3 microM	[39]
[3H]estradiol-17beta-glucuronide	Investigative	Chinese hamster ovary (CHO) cells-OATP1B1	Km = 5.4 microM	[40]
[3H]estradiol-17beta-glucuronide	Investigative	Chinese hamster ovary (CHO) cells-OATP1B1	Km = 5.9 microM	[41]
[3H]estradiol-17beta-glucuronide	Investigative	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 2.5 microM	[56]
[3H]estradiol-17beta-glucuronide	Investigative	Human embryonic kidney cells (HEK293)-OATP1B1	Km = 8.29 microM	[47]

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: Liver organic anion transporter 1 (SLCO1B1) DTT Info
• DTP DTT Type: Literature-reported

2 Investigative Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
[3H]estradiol-17beta-glucuronide	DM3KJ45	Discovery agent	N.A.	Investigative	[1]
[3H]estrone-3-sulphate	DMGPF0N	Discovery agent	N.A.	Investigative	[1]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1220).
• [2] Regulation of Organic Anion Transporting Polypeptides (OATP) 1B1- and OATP1B3-Mediated Transport: An Updated Review in the Context of OATP-Mediated Drug-Drug Interactions. Int J Mol Sci. 2018 Mar 14;19(3). pii: E855.
• [3] Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
• [4] Meta-analysis of contribution of genetic polymorphisms in drug-metabolizing enzymes or transporters to axitinib pharmacokinetics. Eur J Clin Pharmacol. 2012 May;68(5):645-55.
• [5] Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos. 2007 Aug;35(8):1400-7.
• [6] Organic Anion Transporter 2-Mediated Hepatic Uptake Contributes to the Clearance of High-Permeability-Low-Molecular-Weight Acid and Zwitterion Drugs: Evaluation Using 25 Drugs. J Pharmacol Exp Ther. 2018 Nov;367(2):322-334.
• [7] Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
• [8] FDA Drug Development and Drug Interactions
• [9] Organic Anion-Transporting Polypeptide and Efflux Transporter-Mediated Hepatic Uptake and Biliary Excretion of Cilostazol and Its Metabolites in Rats and Humans. J Pharm Sci. 2017 Sep;106(9):2515-2523.
• [10] Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
• [11] Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline. J Clin Pharmacol. 2015 May;55(5):534-42.
• [12] The modified dipeptide, enalapril, an angiotensin-converting enzyme inhibitor, is transported by the rat liver organic anion transport protein. Hepatology. 1998 Nov;28(5):1341-6.
• [13] Role of transmembrane domain 10 for the function of organic anion transporting polypeptide 1B1. Protein Sci. 2009 Nov;18(11):2298-306.
• [14] Identification of drugs and drug metabolites as substrates of multidrug resistance protein 2 (MRP2) using triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells. Br J Pharmacol. 2012 Mar;165(6):1836-1847.
• [15] A LC-MS/MS method to quantify the novel cholesterol lowering drug ezetimibe in human serum, urine and feces in healthy subjects genotyped for SLCO1B1. J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Jan 2;830(1):143-50.
• [16] SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not fluvastatin. Clin Pharmacol Ther. 2006 Oct;80(4):356-66.
• [17] Liver Perfusion Modifies Gd-DTPA and Gd-BOPTA Hepatocyte Concentrations Through Transfer Clearances Across Sinusoidal Membranes. Eur J Drug Metab Pharmacokinet. 2017 Aug;42(4):657-667.
• [18] Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56.
• [19] Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1. J Biol Chem. 1999 Jun 11;274(24):17159-63.
• [20] A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999 Dec 24;274(52):37161-8.
• [21] Role of organic anion-transporting polypeptides for cellular mesalazine (5-aminosalicylic acid) uptake. Drug Metab Dispos. 2011 Jun;39(6):1097-102.
• [22] Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
• [23] Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9.
• [24] OATP1B1, OATP1B3, and mrp2 are involved in hepatobiliary transport of olmesartan, a novel angiotensin II blocker. Drug Metab Dispos. 2006 May;34(5):862-9.
• [25] Interaction of human organic anion transporter polypeptides 1B1 and 1B3 with antineoplastic compounds. Eur J Med Chem. 2015 Mar 6;92:723-31.
• [26] Prediction of the in vivo OATP1B1-mediated drug-drug interaction potential of an investigational drug against a range of statins. Eur J Pharm Sci. 2012 Aug 30;47(1):244-55.
• [27] The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B1*15. Pharmacogenet Genomics. 2008 May;18(5):424-33.
• [28] Regorafenib is transported by the organic anion transporter 1B1 and the multidrug resistance protein 2. Biol Pharm Bull. 2015;38(4):582-6.
• [29] Disease-Associated Changes in Drug Transporters May Impact the Pharmacokinetics and/or Toxicity of Drugs: A White Paper From the International Transporter Consortium. Clin Pharmacol Ther. 2018 Nov;104(5):900-915.
• [30] Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J Pharmacol Exp Ther. 2003 Jan;304(1):223-8.
• [31] Involvement of multiple transporters in the hepatobiliary transport of rosuvastatin. Drug Metab Dispos. 2008 Oct;36(10):2014-23.
• [32] Drug-Drug Interactions with the NS3/4A Protease Inhibitor Simeprevir. Clin Pharmacokinet. 2016 Feb;55(2):197-208.
• [33] Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705.
• [34] Pharmacokinetic and pharmacodynamic interactions between the immunosuppressant sirolimus and the lipid-lowering drug ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2010 Jun;87(6):663-7.
• [35] Coleman J., Cox A. and Cowley N. (2011). Side Effects of Drugs Annual. Elsevier.
• [36] Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3. J Lipid Res. 2006 Jun;47(6):1196-202.
• [37] Cellular entry of thyroid hormones by organic anion transporting polypeptides. Best Pract Res Clin Endocrinol Metab. 2007 Jun;21(2):209-21.
• [38] Role of organic anion-transporting polypeptides, OATP-A, OATP-C and OATP-8, in the human placenta-maternal liver tandem excretory pathway for foetal bilirubin. Biochem J. 2003 May 1;371(Pt 3):897-905.
• [39] Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
• [40] Effect of pregnane X receptor ligands on transport mediated by human OATP1B1 and OATP1B3. Eur J Pharmacol. 2008 Apr 14;584(1):57-65.
• [41] Identification, Ki determination and CoMFA analysis of nuclear receptor ligands as competitive inhibitors of OATP1B1-mediated estradiol-17beta-glucuronide transport. Pharmacol Res. 2009 Jul;60(1):50-6.
• [42] Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63.
• [43] Functional characterization of SLCO1B1 (OATP-C) variants, SLCO1B1*5, SLCO1B1*15 and SLCO1B1*15+C1007G, by using transient expression systems of HeLa and HEK293 cells. Pharmacogenet Genomics. 2005 Jul;15(7):513-22.
• [44] effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers. Clin Pharmacol Ther. 2007 Feb;81(2):194-204.
• [45] Substrate-dependent drug-drug interactions between gemfibrozil, fluvastatin and other organic anion-transporting peptide (OATP) substrates on OATP1B1, OATP2B1, and OATP1B3. Drug Metab Dispos. 2007 Aug;35(8):1308-14.
• [46] Multiple human isoforms of drug transporters contribute to the hepatic and renal transport of olmesartan, a selective antagonist of the angiotensin II AT1-receptor. Drug Metab Dispos. 2007 Dec;35(12):2166-76.
• [47] Contribution of OATP2 (OATP1B1) and OATP8 (OATP1B3) to the hepatic uptake of pitavastatin in humans. J Pharmacol Exp Ther. 2004 Oct;311(1):139-46.
• [48] The development, characterization, and application of an OATP1B1 inhibition assay in drug discovery. Drug Metab Dispos. 2012 Aug;40(8):1641-8.
• [49] Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol. 2005 Oct;57(10):1305-11.
• [50] Interactions of rifamycin SV and rifampicin with organic anion uptake systems of human liver. Hepatology. 2002 Jul;36(1):164-72.
• [51] Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology. 2006 May;130(6):1793-806.
• [52] Rosuvastatin pharmacokinetics in heart transplant recipients administered an antirejection regimen including cyclosporine. Clin Pharmacol Ther. 2004 Aug;76(2):167-77.
• [53] Prediction of pharmacokinetic profile of valsartan in human based on in vitro uptake transport data. J Pharmacokinet Pharmacodyn. 2009 Dec;36(6):585-611.
• [54] Involvement of transporters in the hepatic uptake and biliary excretion of valsartan, a selective antagonist of the angiotensin II AT1-receptor, in humans. Drug Metab Dispos. 2006 Jul;34(7):1247-54.
• [55] Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6. J Biol Chem. 2001 Mar 30;276(13):9626-30.
• [56] Effects of fibrates on human organic anion-transporting polypeptide 1B1-, multidrug resistance protein 2- and P-glycoprotein-mediated transport. Xenobiotica. 2005 Jul;35(7):737-53.