Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT27Q3A)

• DTT Name: Solute carrier family 15 member 2 (SLC15A2)
• Synonyms: Peptide transporter 2; PEPT2; Oligopeptide transporter, kidney isoform; Kidney H(+)/peptide cotransporter
• Gene Name: SLC15A2
• DTT Type: Literature-reported target; [1]
• UniProt ID: S15A2_HUMAN
• TTD ID: T52067
• Sequence:
  MNPFQKNESKETLFSPVSIEEVPPRPPSPPKKPSPTICGSNYPLSIAFIVVNEFCERFSY
  YGMKAVLILYFLYFLHWNEDTSTSIYHAFSSLCYFTPILGAAIADSWLGKFKTIIYLSLV
  YVLGHVIKSLGALPILGGQVVHTVLSLIGLSLIALGTGGIKPCVAAFGGDQFEEKHAEER
  TRYFSVFYLSINAGSLISTFITPMLRGDVQCFGEDCYALAFGVPGLLMVIALVVFAMGSK
  IYNKPPPEGNIVAQVFKCIWFAISNRFKNRSGDIPKRQHWLDWAAEKYPKQLIMDVKALT
  RVLFLYIPLPMFWALLDQQGSRWTLQAIRMNRNLGFFVLQPDQMQVLNPLLVLIFIPLFD
  FVIYRLVSKCGINFSSLRKMAVGMILACLAFAVAAAVEIKINEMAPAQPGPQEVFLQVLN
  LADDEVKVTVVGNENNSLLIESIKSFQKTPHYSKLHLKTKSQDFHFHLKYHNLSLYTEHS
  VQEKNWYSLVIREDGNSISSMMVKDTESRTTNGMTTVRFVNTLHKDVNISLSTDTSLNVG
  EDYGVSAYRTVQRGEYPAVHCRTEDKNFSLNLGLLDFGAAYLFVITNNTNQGLQAWKIED
  IPANKMSIAWQLPQYALVTAGEVMFSVTGLEFSYSQAPSSMKSVLQAAWLLTIAVGNIIV
  LVVAQFSGLVQWAEFILFSCLLLVICLIFSIMGYYYVPVKTEDMRGPADKHIPHIQGNMI
  KLETKKTKL
• Function: Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. Transports the dipeptide-like aminopeptidase inhibitor bestatin (By similarity). Can also transport the aminocephalosporin antibiotic cefadroxil (By similarity).
• Reactome Pathway: Proton/oligopeptide cotransporters (R-HSA-427975)

Molecular Interaction Atlas (MIA) of This DTT

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lys[Z(NO2)]-Lys[Z(NO2)]	DMH0Q9V	Discovery agent	N.A.	Investigative	[1]
Lys[Z(NO2)]-Pro	DMJX4GA	Discovery agent	N.A.	Investigative	[2]
[11C]GlySar	DM5Q08F	Discovery agent	N.A.	Investigative	[2]
[14C]GlySar	DMGLQ72	Discovery agent	N.A.	Investigative	[2]
[3H]GlySar	DMFEYLS	Discovery agent	N.A.	Investigative	[2]

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Peptide transporter 2 (SLC15A2) DTP Info
• Gene Name: SLC15A2

23 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aminolevulinic acid hci	DMS4BLQ	Acne vulgaris	ED80	Approved	[3]
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[4]
Ampicillin	DMHWE7P	Acute epiglottitis		Approved	[5]
Benazepril	DMH1M9B	Hypertension	BA00-BA04	Approved	[6]
Bestatin	DM8L9D4	Acute myeloid leukaemia	2A60	Approved	[7]
Cefaclor	DMJXDGC	Bacterial infection	1A00-1C4Z	Approved	[4]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[8]
Cefixime	DMY60I8	Acute gonococcal cervicitis		Approved	[5]
Cefradine	DMUNSWV	Acute otitis media	AB00	Approved	[5]
Ceftibuten	DMWV2AG	Acute otitis media	AB00	Approved	[5]
Cephalexin	DMD5JU8	Acute otitis media	AB00	Approved	[5]
Cyclacillin	DMHSJB4	Bacterial infection	1A00-1C4Z	Approved	[5]
Dicloxacillin	DM8EU0Z	Bacterial infection	1A00-1C4Z	Approved	[5]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[9]
Entecavir	DM7VTQO	Hepatitis B virus infection	1E51.0	Approved	[10]
Fosinopril	DM9NJ52	Chronic heart failure	BD1Z	Approved	[11]
Latamoxef	DMANL0D	Bacterial infection	1A00-1C4Z	Approved	[5]
Moexipril	DM26E4B	Hypertension	BA00-BA04	Approved	[6]
Perindopril	DMOPZDT	Hypertension	BA00-BA04	Approved	[6]
Ramipril	DM2R68E	Acute heart failure	BD10-BD13	Approved	[6]
Spirapril	DM5XLTY	Hypertension	BA00-BA04	Approved	[6]
Trandolapril	DM4L6EU	Chronic heart failure	BD1Z	Approved	[6]
Valaciclovir	DMHKS94	Genital herpes	1A94	Approved	[12]

1 Preclinical Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metampicillin	DMQW5MH	N. A.	N. A.	Preclinical	[5]

References

• [1] Defining minimal structural features in substrates of the H(+)/peptide cotransporter PEPT2 using novel amino acid and dipeptide derivatives. Mol Pharmacol. 2002 Jan;61(1):214-21.
• [2] 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: 985).
• [3] PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes. Brain Res. 2006 Nov 29;1122(1):18-23.
• [4] Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters. Drug Metab Dispos. 2006 Apr;34(4):547-55.
• [5] Transport characteristics of a novel peptide transporter 1 substrate, antihypotensive drug midodrine, and its amino acid derivatives. J Pharmacol Exp Ther. 2006 Jul;318(1):455-60.
• [6] Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41.
• [7] Molecular mechanism of dipeptide and drug transport by the human renal H+/oligopeptide cotransporter hPEPT2. Am J Physiol Renal Physiol. 2008 Jun;294(6):F1422-32.
• [8] Species Differences in Human and Rodent PEPT2-Mediated Transport of Glycylsarcosine and Cefadroxil in Pichia Pastoris Transformants. Drug Metab Dispos. 2017 Feb;45(2):130-136.
• [9] Ethanol inhibits functional activity of the human intestinal dipeptide transporter hPepT1 expressed in Xenopus oocytes. Alcohol Clin Exp Res. 2008 May;32(5):777-84.
• [10] The oligopeptide transporter 2-mediated reabsorption of entecavir in rat kidney. Eur J Pharm Sci. 2014 Feb 14;52:41-7.
• [11] Mechanism of intestinal absorption and renal reabsorption of an orally active ace inhibitor: uptake and transport of fosinopril in cell cultures. Drug Metab Dispos. 2001 Oct;29(10):1307-15.
• [12] Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem Biophys Res Commun. 1998 May 19;246(2):470-5.