Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DT6201N)

• DTP Name: Organic cation transporter 3 (SLC22A3)
• Gene Name: SLC22A3
• UniProt ID: O75751 (S22A3_HUMAN)
• VARIDT ID: DTD0009
• Synonyms: OCT3; EMT; EMTH; Extraneuronal monoamine transporter; SLC22A3; Solute carrier family 22 member 3
• DTP Family:
  Major Facilitator Superfamily (MFS)
  Organic Cation Transporter (OCT) Family
• Tissue Specificity: Highly expressed in the kidney, liver, placenta, heart, and skeletal muscle,to a lesser extent, in other organs including the lung and brain, as well as in cancer-derived cell lines
• Sequence:
  MPSFDEALQRVGEFGRFQRRVFLLLCLTGVTFAFLFVGVVFLGTQPDHYWCRGPSAAALA
  ERCGWSPEEEWNRTAPASRGPEPPERRGRCQRYLLEAANDSASATSALSCADPLAAFPNR
  SAPLVPCRGGWRYAQAHSTIVSEFDLVCVNAWMLDLTQAILNLGFLTGAFTLGYAADRYG
  RIVIYLLSCLGVGVTGVVVAFAPNFPVFVIFRFLQGVFGKGTWMTCYVIVTEIVGSKQRR
  IVGIVIQMFFTLGIIILPGIAYFIPNWQGIQLAITLPSFLFLLYYWVVPESPRWLITRKK
  GDKALQILRRIAKCNGKYLSSNYSEITVTDEEVSNPSFLDLVRTPQMRKCTLILMFAWFT
  SAVVYQGLVMRLGIIGGNLYIDFFISGVVELPGALLILLTIERLGRRLPFAASNIVAGVA
  CLVTAFLPEGIAWLRTTVATLGRLGITMAFEIVYLVNSELYPTTLRNFGVSLCSGLCDFG
  GIIAPFLLFRLAAVWLELPLIIFGILASICGGLVMLLPETKGIALPETVDDVEKLGSPHS
  CKCGRNKKTPVSRSHL
• Function: This transporter may play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain and mediate potential-dependent transport of a variety of organic cations.
• Endogenous Substrate(s): Monoamines
• TCDB ID: 2.A.1.19.24
• Gene ID: 6581
• Reactome Pathway:
  Organic cation transport (R-HSA-549127)
  Abacavir transmembrane transport (R-HSA-2161517)

Molecular Interaction Atlas (MIA) of This DTP

10 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetylcholine	DMDF79Z	Cataract	9B10	Approved	[1]
Amphetamine	DMSZQAK	Attention deficit hyperactivity disorder	6A05.Z	Approved	[2]
Clonidine	DM6RZ9Q	Hypertension	BA00-BA04	Approved	[3]
Entecavir	DM7VTQO	Hepatitis B virus infection	1E51.0	Approved	[4]
Epinephrine	DM3KJBC	Allergy	4A80-4A85	Approved	[5]
Ergotidine	DM78IME	Respiratory allergy	4A80	Approved	[5]
Metformin	DM89QE1	Type-2 diabetes	5A11	Approved	[6]
Norepinephrine	DMOUC09	Sepsis	1G40-1G41	Approved	[5]
Propranolol	DM79NTF	Migraine	8A80	Approved	[3]
Sodium chloride	DMM3950	Skin burns	ME65.0	Approved	[7]

1 Discontinued Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Etilefrine	DM67PWD	Cardiovascular disease	BA00-BE2Z	Withdrawn from market	[8]

1 Preclinical Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
N-methylpyridinium	DMVUKEW	Colon cancer	2B90.Z	Preclinical	[9]

1 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Guanidine	DM4GO8H	LambertEaton myasthenic syndrome	8C62	Investigative	[9]

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	6.60E-02	-7.76E-02	-2.64E-01
Adrenocortical carcinoma	2D11.Z	Kidney	4.92E-01	-5.91E-02	-1.15E-01
Alopecia	ED70	Skin from scalp	8.45E-01	-1.21E-01	-2.82E-01
Alzheimer's disease	8A20	Entorhinal cortex	2.05E-04	1.58E-01	6.95E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	4.94E-01	-6.64E-02	-2.59E-01
Aortic stenosis	BB70	Calcified aortic valve	4.23E-01	-1.81E-01	-1.29E-01
Apnea	7A40	Hyperplastic tonsil	3.79E-01	2.50E-01	8.56E-01
Arthropathy	FA00-FA5Z	Peripheral blood	3.84E-01	-1.25E-02	-7.88E-02
Asthma	CA23	Nasal and bronchial airway	1.40E-02	-8.48E-02	-2.03E-01
Atopic dermatitis	EA80	Skin	2.38E-03	2.76E-01	1.05E+00
Autism	6A02	Whole blood	9.86E-04	1.94E-01	1.10E+00
Autoimmune uveitis	9A96	Peripheral monocyte	1.30E-01	2.28E-01	7.73E-01
Autosomal dominant monocytopenia	4B04	Whole blood	9.73E-01	9.86E-02	3.21E-01
Bacterial infection of gingival	1C1H	Gingival tissue	8.93E-12	-3.10E-01	-1.07E+00
Batten disease	5C56.1	Whole blood	2.46E-01	-1.71E-01	-1.17E+00
Behcet's disease	4A62	Peripheral blood	2.61E-01	-2.84E-02	-1.32E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	3.01E-01	1.35E-02	7.65E-02
Bladder cancer	2C94	Bladder tissue	3.43E-01	1.25E-02	2.51E-02
Breast cancer	2C60-2C6Z	Breast tissue	9.29E-22	-2.35E-01	-4.22E-01
Cardioembolic stroke	8B11.20	Whole blood	8.60E-02	-7.47E-02	-5.28E-01
Cervical cancer	2C77	Cervical tissue	7.54E-05	-5.43E-01	-1.25E+00
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	1.14E-02	-1.02E-01	-8.63E-01
Chronic hepatitis C	1E51.1	Whole blood	9.77E-02	9.50E-02	7.68E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	3.81E-01	7.81E-03	2.49E-02
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	5.70E-02	6.96E-02	2.45E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	7.48E-01	1.15E-01	2.62E-01
Colon cancer	2B90	Colon tissue	8.10E-83	1.12E+00	2.72E+00
Coronary artery disease	BA80-BA8Z	Peripheral blood	5.94E-01	-1.03E-01	-3.63E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	7.34E-01	-1.21E-02	-6.92E-02
Endometriosis	GA10	Endometrium tissue	7.25E-01	-2.03E-01	-2.88E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	7.13E-01	4.71E-02	4.47E-01
Familial hypercholesterolemia	5C80.00	Whole blood	6.64E-01	8.11E-03	4.57E-02
Gastric cancer	2B72	Gastric tissue	4.77E-01	-2.64E-01	-3.20E-01
Glioblastopma	2A00.00	Nervous tissue	4.29E-14	2.08E-01	4.01E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	5.04E-03	-5.69E-01	-9.02E-01
Head and neck cancer	2D42	Head and neck tissue	2.91E-12	3.63E-01	7.09E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	9.04E-02	2.10E-01	8.20E-01
Huntington's disease	8A01.10	Whole blood	1.83E-01	-6.15E-02	-2.24E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	2.02E-01	-3.52E-01	-8.19E-01
Immunodeficiency	4A00-4A20	Peripheral blood	3.38E-03	-2.49E-01	-2.23E+00
Influenza	1.00E+30	Whole blood	5.56E-04	1.04E+00	7.15E+00
Interstitial cystitis	GC00.3	Bladder tissue	2.24E-01	3.81E-01	1.07E+00
Intracranial aneurysm	8B01.0	Intracranial artery	8.59E-06	-2.24E+00	-3.44E+00
Irritable bowel syndrome	DD91.0	Rectal colon tissue	1.09E-02	1.31E-01	3.01E-01
Ischemic stroke	8B11	Peripheral blood	2.30E-01	-5.21E-02	-1.98E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	1.78E-03	8.69E-02	4.75E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	3.82E-01	2.93E-02	4.28E-02
Lateral sclerosis	8B60.4	Skin	7.95E-01	-4.16E-02	-3.61E-01
Liver cancer	2C12.0	Liver tissue	4.42E-01	2.61E-02	4.93E-02
Liver failure	DB99.7-DB99.8	Liver tissue	1.09E-03	-1.45E+00	-3.71E+00
Lung cancer	2C25	Lung tissue	1.58E-14	-3.86E-01	-7.54E-01
Lupus erythematosus	4A40	Whole blood	6.87E-01	-4.38E-02	-1.72E-01
Major depressive disorder	6A70-6A7Z	Whole blood	4.40E-01	-3.55E-03	-1.23E-02
Major depressive disorder	6A70-6A7Z	Hippocampus	3.72E-01	5.29E-02	3.62E-01
Melanoma	2C30	Skin	1.29E-02	-5.10E-01	-6.81E-01
Multiple myeloma	2A83.1	Bone marrow	1.04E-03	3.25E-01	1.74E+00
Multiple myeloma	2A83.1	Peripheral blood	3.15E-01	1.07E-01	3.82E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	3.74E-01	-1.47E-01	-7.75E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	4.75E-01	-2.41E-02	-1.19E-01
Myelofibrosis	2A20.2	Whole blood	6.78E-02	7.57E-02	7.64E-01
Myocardial infarction	BA41-BA50	Peripheral blood	4.65E-01	3.01E-02	7.86E-02
Myopathy	8C70.6	Muscle tissue	2.62E-04	-9.27E-01	-2.16E+00
Neonatal sepsis	KA60	Whole blood	5.48E-03	-8.31E-02	-2.93E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	4.24E-02	-3.88E-01	-2.23E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	6.03E-01	1.94E-01	5.84E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	2.10E-01	2.66E-01	1.53E+00
Olive pollen allergy	CA08.00	Peripheral blood	2.96E-01	1.30E-01	8.68E-01
Oral cancer	2B6E	Oral tissue	9.88E-01	2.19E-01	2.32E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	2.98E-02	-6.62E-01	-1.06E+00
Osteoporosis	FB83.1	Bone marrow	6.44E-01	1.74E-01	3.06E-01
Ovarian cancer	2C73	Ovarian tissue	2.35E-04	-1.37E+00	-2.11E+00
Pancreatic cancer	2C10	Pancreas	1.87E-02	7.39E-01	7.71E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	2.42E-01	2.18E-01	8.46E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	6.17E-04	-1.86E-01	-1.61E+00
Pituitary cancer	2D12	Pituitary tissue	1.52E-02	-4.55E-01	-1.22E+00
Pituitary gonadotrope tumour	2D12	Pituitary tissue	2.25E-02	-2.75E-01	-1.17E+00
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	3.40E-01	1.14E-01	2.35E-01
Polycythemia vera	2A20.4	Whole blood	9.03E-01	1.55E-02	1.70E-01
Pompe disease	5C51.3	Biceps muscle	4.13E-01	-5.36E-04	-8.38E-04
Preterm birth	KA21.4Z	Myometrium	4.88E-02	-5.15E-01	-2.28E+00
Prostate cancer	2C82	Prostate	7.22E-01	1.91E-01	2.22E-01
Psoriasis	EA90	Skin	1.68E-07	4.84E-01	1.17E+00
Rectal cancer	2B92	Rectal colon tissue	2.29E-05	1.34E+00	4.40E+00
Renal cancer	2C90-2C91	Kidney	1.94E-02	-1.79E-01	-4.19E-01
Retinoblastoma	2D02.2	Uvea	6.37E-02	1.79E-01	8.74E-01
Rheumatoid arthritis	FA20	Synovial tissue	3.12E-04	-1.10E+00	-2.58E+00
Rhinovirus infection	CA42.1	Nasal epithelium tissue	1.09E-01	-3.04E-02	-2.55E-01
Schizophrenia	6A20	Prefrontal cortex	8.12E-01	-1.58E-02	-6.13E-02
Schizophrenia	6A20	Superior temporal cortex	2.09E-01	6.85E-02	4.90E-01
Scleroderma	4A42.Z	Whole blood	1.51E-08	-2.18E-01	-3.48E+00
Seizure	8A60-8A6Z	Whole blood	6.63E-01	2.96E-02	2.29E-01
Sensitive skin	EK0Z	Skin	7.41E-01	2.80E-02	1.20E-01
Sepsis with septic shock	1G41	Whole blood	2.07E-02	5.99E-02	2.49E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	3.03E-01	-5.68E-03	-9.81E-02
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	8.26E-02	-1.40E-01	-3.23E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	4.64E-01	-1.66E-01	-2.29E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	2.76E-02	-5.77E-01	-3.71E+00
Skin cancer	2C30-2C3Z	Skin	1.38E-46	-9.03E-01	-1.79E+00
Thrombocythemia	3B63	Whole blood	1.33E-02	7.54E-02	7.91E-01
Thrombocytopenia	3B64	Whole blood	8.60E-01	-5.61E-03	-1.74E-02
Thyroid cancer	2D10	Thyroid	9.01E-01	8.69E-03	1.68E-02
Tibial muscular dystrophy	8C75	Muscle tissue	3.92E-01	-3.33E-01	-5.15E-01
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	4.35E-02	2.19E-01	1.76E+00
Type 2 diabetes	5A11	Liver tissue	6.65E-02	1.90E-01	7.55E-01
Ureter cancer	2C92	Urothelium	8.06E-01	-1.00E-01	-3.48E-01
Uterine cancer	2C78	Endometrium tissue	2.73E-13	-7.18E-01	-9.28E-01
Vitiligo	ED63.0	Skin	4.29E-02	-1.48E-01	-9.09E-01

Drug Affinity of This DTP Assessed by Cell Line

Approved Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
Epinephrine	Approved	Human embryonic kidney cells (HEK293)-OCT3	Km = 240 microM	[5]
Ergotidine	Approved	Human embryonic kidney cells (HEK293)-OCT3	Km = 180 microM	[10]
Ergotidine	Approved	Human embryonic kidney cells (HEK293)-OCT3	Km = 220 microM	[5]
Metformin	Approved	Chinese hamster ovary (CHO) cells-OCT3	Km = 2260 microM	[6]
Norepinephrine	Approved	Human embryonic kidney cells (HEK293)-OCT3	Km = 510 microM	[11]
Norepinephrine	Approved	Human embryonic kidney cells (HEK293)-OCT3	Km = 2630 microM	[5]

Discontinued Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
Etilefrine	Withdrawn from market	Chinese hamster ovary (CHO) cells-OCT3	Km = 2800 microM	[8]

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: Organic cation transporter 3 (OCT3) DTT Info
• DTP DTT Type: Literature-reported

References

• [1] Organic cation transporters: physiology, toxicology and special focus on ethidium as a novel substrate. Curr Drug Metab. 2009 Jul;10(6):617-31.
• [2] Interaction of organic cation transporter 3 (SLC22A3) and amphetamine. J Neurochem. 2010 Jul;114(1):142-9.
• [3] Influx Transport of Cationic Drug at the Blood-Retinal Barrier: Impact on the Retinal Delivery of Neuroprotectants. Biol Pharm Bull. 2017;40(8):1139-1145.
• [4] Multiple SLC and ABC Transporters Contribute to the Placental Transfer of Entecavir. Drug Metab Dispos. 2017 Mar;45(3):269-278.
• [5] Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology. 2006 Jun;50(8):941-52.
• [6] Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Hepatology. 2009 Oct;50(4):1227-40.
• [7] Organic cation transporter 3 (Slc22a3) is implicated in salt-intake regulation. J Neurosci. 2004 Mar 17;24(11):2846-51.
• [8] Drug specificity and intestinal membrane localization of human organic cation transporters (OCT). Biochem Pharmacol. 2005 Dec 5;70(12):1851-60.
• [9] Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol. 2000 Sep;279(3):F449-58.
• [10] Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol. 1999 Jul;56(1):1-10.
• [11] Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. Nat Neurosci. 1998 Sep;1(5):349-51.