Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTN1J82)

• DTT Name: Monocarboxylate transporter 1 (SLC16A1)
• Synonyms: Solute carrier family 16 member 1; MCT1; MCT 1
• Gene Name: SLC16A1
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Major facilitator
• UniProt ID: MOT1_HUMAN
• TTD ID: T95842
• Sequence:
  MPPAVGGPVGYTPPDGGWGWAVVIGAFISIGFSYAFPKSITVFFKEIEGIFHATTSEVSW
  ISSIMLAVMYGGGPISSILVNKYGSRIVMIVGGCLSGCGLIAASFCNTVQQLYVCIGVIG
  GLGLAFNLNPALTMIGKYFYKRRPLANGLAMAGSPVFLCTLAPLNQVFFGIFGWRGSFLI
  LGGLLLNCCVAGALMRPIGPKPTKAGKDKSKASLEKAGKSGVKKDLHDANTDLIGRHPKQ
  EKRSVFQTINQFLDLTLFTHRGFLLYLSGNVIMFFGLFAPLVFLSSYGKSQHYSSEKSAF
  LLSILAFVDMVARPSMGLVANTKPIRPRIQYFFAASVVANGVCHMLAPLSTTYVGFCVYA
  GFFGFAFGWLSSVLFETLMDLVGPQRFSSAVGLVTIVECCPVLLGPPLLGRLNDMYGDYK
  YTYWACGVVLIISGIYLFIGMGINYRLLAKEQKANEQKKESKEEETSIDVAGKPNEVTKA
  AESPDQKDTDGGPKEEESPV
• Function: Catalyzes 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. Proton-coupled monocarboxylate transporter.
• 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

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Monocarboxylate transporter 1 (SLC16A1) DTP Info
• Gene Name: SLC16A1

5 Approved Drug(s) Transported by This DTT

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

1 Clinical Trial Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Gabapentin enacarbil	DMJY2TM	Postherpetic neuralgia	1E91.5	Phase 2	[6]

5 Investigative Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
biotin	DMKMCE1	Discovery agent	N.A.	Investigative	[7]
Butanoic Acid	DMTAJP7	Discovery agent	N.A.	Investigative	[6]
Hydroxyacetic Acid	DMQFBH6	Discovery agent	N.A.	Investigative	[8]
Milchsaure	DM462BT	Pruritus	EC90	Investigative	[9]
Pyroglutamic Acid	DMROZUA	Discovery agent	N.A.	Investigative	[10]

References

• [1] Expression of monocarboxylate transporter MCT1 in normal and neoplastic human CNS tissues. Neuroreport. 2001 Mar 26;12(4):761-5.
• [2] H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine. Exp Physiol. 2007 Jul;92(4):603-19.
• [3] 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.
• [4] Flavonoids modulate monocarboxylate transporter-1-mediated transport of gamma-hydroxybutyrate in vitro and in vivo. Drug Metab Dispos. 2007 Feb;35(2):201-8.
• [5] 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.
• [6] 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.
• [7] Biotin. Biofactors. 2009 Jan-Feb;35(1):36-46.
• [8] Cidofovir peptide conjugates as prodrugs. Journal of Organometallic Chemistry, 2005, 690(10):2673-2678.
• [9] Distribution of monocarboxylate transporters MCT1-MCT8 in rat tissues and human skeletal muscle. Appl Physiol Nutr Metab. 2006 Feb;31(1):31-9.
• [10] Interaction of atorvastatin with the human glial transporter SLC16A1. Eur J Pharmacol. 2016 Oct 5;788:248-254.