Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DT342ZG)

• DTP Name: Monocarboxylate transporter 1 (SLC16A1)
• Gene Name: SLC16A1
• UniProt ID: P53985 (MOT1_HUMAN)
• VARIDT ID: DTD0100
• Synonyms: HHF7; MCT; MCT 1; MCT1; MCT1D; SLC16A1; Solute carrier family 16 member 1; hMCT1
• DTP Family:
  Major Facilitator Superfamily (MFS)
  Monocarboxylate Transporter (MCT) Family
• Tissue Specificity: Detected in heart and in blood lymphocytes andmonocytes (at protein level). Widely expressed.
• Sequence:
  MPPAVGGPVGYTPPDGGWGWAVVIGAFISIGFSYAFPKSITVFFKEIEGIFHATTSEVSW
  ISSIMLAVMYGGGPISSILVNKYGSRIVMIVGGCLSGCGLIAASFCNTVQQLYVCIGVIG
  GLGLAFNLNPALTMIGKYFYKRRPLANGLAMAGSPVFLCTLAPLNQVFFGIFGWRGSFLI
  LGGLLLNCCVAGALMRPIGPKPTKAGKDKSKASLEKAGKSGVKKDLHDANTDLIGRHPKQ
  EKRSVFQTINQFLDLTLFTHRGFLLYLSGNVIMFFGLFAPLVFLSSYGKSQHYSSEKSAF
  LLSILAFVDMVARPSMGLVANTKPIRPRIQYFFAASVVANGVCHMLAPLSTTYVGFCVYA
  GFFGFAFGWLSSVLFETLMDLVGPQRFSSAVGLVTIVECCPVLLGPPLLGRLNDMYGDYK
  YTYWACGVVLIISGIYLFIGMGINYRLLAKEQKANEQKKESKEEETSIDVAGKPNEVTKA
  AESPDQKDTDGGPKEEESPV
• Function: This proton-coupled transporter can mediates the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate. Depending on the tissue and on cicumstances, mediates the import or export of lactic acid and ketone bodies. Required for normal nutrient assimilation, increase of white adipose tissue and body weight gain when on a high-fat diet. Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate, small molecules that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis.
• Endogenous Substrate(s): Monocarboxylates
• TCDB ID: 2.A.1.13.1
• Gene ID: 6566
• Reactome Pathway:
  Proton-coupled monocarboxylate transport (R-HSA-433692)
  Defective SLC16A1 causes symptomatic deficiency in lactate transport (SDLT) (R-HSA-5619070)
  Pyruvate metabolism (R-HSA-70268)
  Aspirin ADME (R-HSA-9749641)
  Basigin interactions (R-HSA-210991)
• BioCyc Pathway: MetaCyc:ENSG00000155380-MON

Molecular Interaction Atlas (MIA) of This DTP

5 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[1]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[2]
Gamma Hydroxybutyric Acid	DMGBKVD	Narcolepsy	7A20	Approved	[3]
Pyruvic acid	DM7Q41G	Malnutrition	5B50-5B71	Approved	[4]
Salicyclic acid	DM2F8XZ	Acne vulgaris	ED80	Approved	[1]

1 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Gabapentin enacarbil	DMJY2TM	Postherpetic neuralgia	1E91.5	Phase 2	[5]

5 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
biotin	DMKMCE1	Discovery agent	N.A.	Investigative	[6]
Butanoic Acid	DMTAJP7	Discovery agent	N.A.	Investigative	[5]
Hydroxyacetic Acid	DMQFBH6	Discovery agent	N.A.	Investigative	[7]
Milchsaure	DM462BT	Pruritus	EC90	Investigative	[8]
Pyroglutamic Acid	DMROZUA	Discovery agent	N.A.	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	7.74E-02	1.15E-03	3.19E-03
Adrenocortical carcinoma	2D11.Z	Kidney	2.54E-05	2.76E-01	7.51E-01
Alopecia	ED70	Skin from scalp	7.87E-01	2.29E-05	5.36E-05
Alzheimer's disease	8A20	Entorhinal cortex	2.27E-02	4.13E-01	6.05E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	6.78E-01	-3.25E-02	-8.35E-02
Aortic stenosis	BB70	Calcified aortic valve	2.90E-01	-1.32E-01	-4.22E-01
Apnea	7A40	Hyperplastic tonsil	8.21E-03	-9.41E-01	-1.54E+00
Arthropathy	FA00-FA5Z	Peripheral blood	3.09E-02	-1.75E-01	-6.88E-01
Asthma	CA23	Nasal and bronchial airway	4.96E-05	3.95E-01	6.42E-01
Atopic dermatitis	EA80	Skin	2.67E-03	3.11E-01	1.06E+00
Autism	6A02	Whole blood	3.28E-01	-1.38E-01	-4.61E-01
Autoimmune uveitis	9A96	Peripheral monocyte	8.37E-01	-2.22E-01	-7.39E-01
Autosomal dominant monocytopenia	4B04	Whole blood	4.08E-01	5.63E-02	2.74E-01
Bacterial infection of gingival	1C1H	Gingival tissue	2.95E-01	2.12E-01	4.56E-01
Batten disease	5C56.1	Whole blood	2.16E-01	5.39E-02	2.62E-01
Behcet's disease	4A62	Peripheral blood	8.42E-01	1.30E-01	3.21E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	2.75E-02	2.62E-01	5.08E-01
Bladder cancer	2C94	Bladder tissue	4.93E-02	5.53E-01	6.83E-01
Breast cancer	2C60-2C6Z	Breast tissue	7.28E-01	-2.66E-01	-4.63E-01
Cardioembolic stroke	8B11.20	Whole blood	5.37E-06	6.20E-01	1.26E+00
Cervical cancer	2C77	Cervical tissue	4.23E-04	5.77E-01	7.73E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	7.37E-01	2.53E-02	5.76E-02
Chronic hepatitis C	1E51.1	Whole blood	2.28E-01	-1.79E-01	-6.64E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	7.59E-01	-1.23E-03	-3.26E-03
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	7.26E-01	4.05E-02	2.23E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	1.28E-01	3.15E-01	9.11E-01
Colon cancer	2B90	Colon tissue	8.00E-13	-7.07E-01	-7.63E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	3.00E-01	3.33E-02	3.15E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	7.44E-01	5.13E-02	1.41E-01
Endometriosis	GA10	Endometrium tissue	1.17E-01	-6.12E-01	-9.72E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	4.48E-01	1.97E-02	5.95E-02
Familial hypercholesterolemia	5C80.00	Whole blood	1.39E-04	6.49E-01	2.64E+00
Gastric cancer	2B72	Gastric tissue	1.12E-01	6.72E-01	1.88E+00
Glioblastopma	2A00.00	Nervous tissue	3.00E-80	1.11E+00	1.60E+00
Glioma	2A00.0Y-2A00.0Z	White matter tissue	1.28E-04	6.79E-01	1.69E+00
Head and neck cancer	2D42	Head and neck tissue	4.68E-65	2.96E+00	3.93E+00
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	7.34E-01	2.55E-01	4.16E-01
Huntington's disease	8A01.10	Whole blood	8.69E-01	-6.60E-02	-5.80E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	9.12E-01	-1.82E-01	-2.70E-01
Immunodeficiency	4A00-4A20	Peripheral blood	5.26E-05	5.12E-01	8.36E+00
Influenza	1.00E+30	Whole blood	1.28E-04	-1.37E+00	-6.13E+00
Interstitial cystitis	GC00.3	Bladder tissue	5.03E-02	4.69E-01	1.21E+00
Intracranial aneurysm	8B01.0	Intracranial artery	8.13E-03	5.61E-01	1.08E+00
Irritable bowel syndrome	DD91.0	Rectal colon tissue	1.09E-01	-1.15E-01	-2.16E-01
Ischemic stroke	8B11	Peripheral blood	5.04E-01	-9.56E-02	-3.62E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	2.29E-03	2.26E-01	3.21E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	2.16E-01	-2.79E-01	-4.77E-01
Lateral sclerosis	8B60.4	Skin	4.89E-01	6.25E-02	2.14E-01
Liver cancer	2C12.0	Liver tissue	7.42E-01	2.57E-02	3.76E-02
Liver failure	DB99.7-DB99.8	Liver tissue	3.57E-03	-1.24E+00	-1.83E+00
Lung cancer	2C25	Lung tissue	6.42E-35	3.17E-01	6.92E-01
Lupus erythematosus	4A40	Whole blood	3.35E-01	2.26E-01	2.82E-01
Major depressive disorder	6A70-6A7Z	Whole blood	9.27E-01	3.92E-03	8.85E-03
Major depressive disorder	6A70-6A7Z	Hippocampus	1.90E-01	6.86E-02	1.47E-01
Melanoma	2C30	Skin	7.97E-03	3.42E-01	5.24E-01
Multiple myeloma	2A83.1	Bone marrow	8.52E-06	8.18E-01	3.67E+00
Multiple myeloma	2A83.1	Peripheral blood	3.14E-01	-5.95E-01	-9.39E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	5.02E-01	-3.79E-01	-4.77E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	2.33E-01	1.14E-01	2.04E-01
Myelofibrosis	2A20.2	Whole blood	1.76E-02	6.46E-01	4.33E+00
Myocardial infarction	BA41-BA50	Peripheral blood	9.46E-01	-1.54E-01	-1.27E-01
Myopathy	8C70.6	Muscle tissue	5.67E-02	-1.19E-01	-4.39E-01
Neonatal sepsis	KA60	Whole blood	1.71E-02	5.10E-02	1.24E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	1.04E-05	1.74E+00	2.79E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	2.97E-01	-2.35E-01	-4.50E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	9.17E-02	-3.75E-01	-7.38E-01
Olive pollen allergy	CA08.00	Peripheral blood	3.98E-01	-1.64E-01	-3.11E-01
Oral cancer	2B6E	Oral tissue	3.43E-10	1.66E+00	1.72E+00
Osteoarthritis	FA00-FA0Z	Synovial tissue	7.98E-01	1.26E-01	1.35E-01
Osteoporosis	FB83.1	Bone marrow	4.46E-01	-2.31E-01	-8.01E-01
Ovarian cancer	2C73	Ovarian tissue	5.11E-01	4.06E-01	5.41E-01
Pancreatic cancer	2C10	Pancreas	1.34E-03	5.89E-01	7.09E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	6.45E-01	2.60E-01	5.67E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	3.36E-02	1.01E-01	3.74E-01
Pituitary cancer	2D12	Pituitary tissue	1.79E-02	5.42E-01	1.01E+00
Pituitary gonadotrope tumour	2D12	Pituitary tissue	3.97E-02	8.15E-01	1.31E+00
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	1.89E-01	-2.81E-01	-6.15E-01
Polycythemia vera	2A20.4	Whole blood	1.52E-03	3.69E-02	2.43E-01
Pompe disease	5C51.3	Biceps muscle	7.80E-02	-4.56E-01	-1.25E+00
Preterm birth	KA21.4Z	Myometrium	7.79E-03	1.71E+00	2.01E+00
Prostate cancer	2C82	Prostate	1.59E-05	2.21E+00	1.89E+00
Psoriasis	EA90	Skin	2.20E-28	1.45E+00	2.18E+00
Rectal cancer	2B92	Rectal colon tissue	4.14E-01	-6.59E-01	-6.36E-01
Renal cancer	2C90-2C91	Kidney	5.79E-05	2.61E+00	2.38E+00
Retinoblastoma	2D02.2	Uvea	1.31E-04	-1.66E+00	-2.86E+00
Rheumatoid arthritis	FA20	Synovial tissue	2.86E-01	-1.74E-01	-1.76E-01
Rhinovirus infection	CA42.1	Nasal epithelium tissue	1.83E-02	4.55E-02	2.52E-01
Schizophrenia	6A20	Prefrontal cortex	1.93E-01	5.79E-02	1.09E-01
Schizophrenia	6A20	Superior temporal cortex	5.25E-01	4.22E-02	6.53E-02
Scleroderma	4A42.Z	Whole blood	4.57E-01	-1.19E-01	-5.97E-01
Seizure	8A60-8A6Z	Whole blood	7.56E-01	-1.21E-01	-2.40E-01
Sensitive skin	EK0Z	Skin	6.63E-01	0.00E+00	0.00E+00
Sepsis with septic shock	1G41	Whole blood	7.73E-07	9.01E-02	3.03E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	4.03E-01	2.34E-01	6.14E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	8.63E-02	2.26E-01	9.93E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	3.66E-02	8.47E-01	2.46E+00
Sjogren's syndrome	4A43.2	Salivary gland tissue	2.65E-01	1.94E-01	5.92E-01
Skin cancer	2C30-2C3Z	Skin	6.77E-71	1.80E+00	2.46E+00
Thrombocythemia	3B63	Whole blood	1.89E-01	7.19E-02	4.78E-01
Thrombocytopenia	3B64	Whole blood	5.50E-01	-4.53E-01	-3.70E-01
Thyroid cancer	2D10	Thyroid	4.03E-19	3.97E-01	9.15E-01
Tibial muscular dystrophy	8C75	Muscle tissue	3.81E-01	-3.11E-01	-4.05E-01
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	1.49E-02	8.22E-01	1.87E+00
Type 2 diabetes	5A11	Liver tissue	4.70E-01	-1.15E-01	-2.35E-01
Ureter cancer	2C92	Urothelium	9.32E-01	-4.53E-02	-2.13E-01
Uterine cancer	2C78	Endometrium tissue	3.49E-01	1.53E-01	1.58E-01
Vitiligo	ED63.0	Skin	3.39E-01	-6.90E-02	-2.09E-01

Drug Affinity of This DTP Assessed by Cell Line

Investigative Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
Pyroglutamic Acid	Investigative	Oocytes-MCT1	Km = 4.0 microM	[9]

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: Monocarboxylate transporter 1 (SLC16A1) DTT Info
• DTP DTT Type: Literature-reported

References

• [1] H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine. Exp Physiol. 2007 Jul;92(4):603-19.
• [2] Circadian rhythms in gene expression: Relationship to physiology, disease, drug disposition and drug action. Adv Drug Deliv Rev. 2010 Jul 31;62(9-10):904-17.
• [3] Flavonoids modulate monocarboxylate transporter-1-mediated transport of gamma-hydroxybutyrate in vitro and in vivo. Drug Metab Dispos. 2007 Feb;35(2):201-8.
• [4] AR-C155858 is a potent inhibitor of monocarboxylate transporters MCT1 and MCT2 that binds to an intracellular site involving transmembrane helices 7-10. Biochem J. 2010 Jan 15;425(3):523-30.
• [5] Overview of the proton-coupled MCT (SLC16A) family of transporters: characterization, function and role in the transport of the drug of abuse gamma-hydroxybutyric acid. AAPS J. 2008 Jun;10(2):311-21.
• [6] Biotin. Biofactors. 2009 Jan-Feb;35(1):36-46.
• [7] Cidofovir peptide conjugates as prodrugs. Journal of Organometallic Chemistry, 2005, 690(10):2673-2678.
• [8] Distribution of monocarboxylate transporters MCT1-MCT8 in rat tissues and human skeletal muscle. Appl Physiol Nutr Metab. 2006 Feb;31(1):31-9.
• [9] Interaction of atorvastatin with the human glial transporter SLC16A1. Eur J Pharmacol. 2016 Oct 5;788:248-254.