Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMKSTWR)

• Drug Name: L-Proline Drug Info
• Synonyms: Carboxypyrrolidine; Pro; Prolina; Prolinum; Prolina [Spanish]; Prolinum [Latin]; CB 1707; L-Prolin; PRO (IUPACabbreviation); Proline (USP); Proline (VAN); Proline [USAN:INN]; H-Pro-OH; L-Proline (JAN); L-Proline-15N; L-alpha-Pyrrolidinecarboxylic acid; L-Proline, labeled with carbon-14; L-Pyrrolidine-2-carboxylic acid; L-(2,3-3H)Proline; (-)-(S)-Proline; (-)-2-Pyrrolidinecarboxylic acid; (-)-Proline (S)-2-Carboxypyrrolidine; (2S)-pyrrolidine-2-carboxylic acid; (S)-2-Carboxypyrrolidine; (S)-2-Pyrrolidinecarboxylic acid; (S)-Proline; (S)-Pyrrolidine-2-carboxylic acid; 2-pyrrolidinecarboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Malnutrition	5B50-5B71	Approved	[1]

• Therapeutic Class: Dietary supplement
• Cross-matching ID:
  PubChem CID: 145742
  ChEBI ID: CHEBI:17203
  CAS Number: CAS 4305-67-3
  TTD Drug ID: DMKSTWR
  VARIDT Drug ID: DR00179

Molecule-Related Drug Atlas

Drug(s) Targeting Rotamase B (PPIB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,4-Dithiothreitol	DMIFOXE	Discovery agent	N.A.	Investigative	[9]

Drug(s) Targeting Rotamase A (PPIA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3-[3-(3-benzyloxy-pyridin-2-yl)-ureido]-benzamide	DM60YGF	Discovery agent	N.A.	Investigative	[10]
(3r)-1-Acetyl-3-Methylpiperidine	DM49YTN	Discovery agent	N.A.	Investigative	[9]
7-AMINO-4-METHYL-CHROMEN-2-ONE	DMC8O3Z	Discovery agent	N.A.	Investigative	[11]
1-(3-benzyloxy-pyridin-2-yl)-3-phenyl-urea	DMDZAVU	Discovery agent	N.A.	Investigative	[10]
Ethyl Oxo(Piperidin-1-Yl)Acetate	DM9KF0H	Discovery agent	N.A.	Investigative	[11]
4-[3-(3-benzyloxy-pyridin-2-yl)-ureido]-benzamide	DMOPRQ7	Discovery agent	N.A.	Investigative	[10]

Drug(s) Transported By Proton-coupled amino acid transporter 1 (SLC36A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Glycine	DMIOZ29	Allergic rhinitis	CA08.0	Approved	[12]
Cycloserine	DMT1I52	Bacterial infection	1A00-1C4Z	Approved	[13]
Aminolevulinic acid hci	DMS4BLQ	Acne vulgaris	ED80	Approved	[14]
Gaboxadol	DMI53FU	Insomnia	7A00-7A0Z	Approved	[15]
Vigabatrin	DMYT0OG	Alcohol dependence	6C40.2	Approved	[16]

Drug(s) Transported By Proton-coupled amino acid transporter 4 (SLC36A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-Tryptophan	DMIBH7M	Depression	6A70-6A7Z	Approved	[5]

Drug(s) Transported By Na(+)/Cl(-) betaine/GABA transporter (SLC6A12)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[17]
Glycine	DMIOZ29	Allergic rhinitis	CA08.0	Approved	[6]
Betaine	DMGRZW2	Cystitis	GC00	Approved	[18]
CHOLINE	DM5D9YK	Insomnia	7A00-7A0Z	Investigative	[6]

Drug(s) Transported By L-type amino acid transporter 2 (SLC7A8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-Tryptophan	DMIBH7M	Depression	6A70-6A7Z	Approved	[7]
Glycine	DMIOZ29	Allergic rhinitis	CA08.0	Approved	[7]
L-Alanine	DMZDN4W	Dietary shortage	5B5K	Approved	[7]
L-Phenylalanine	DMQXI9F	Malnutrition	5B50-5B71	Approved	[19]
L-Tyrosine	DM9O8DT	Malnutrition	5B50-5B71	Approved	[7]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Rotamase A (PPIA)	TTL2ADK	PPIA_HUMAN	Binder	[2]
Rotamase B (PPIB)	TT6ZFQ4	PPIB_HUMAN	Binder	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Sodium-dependent proline transporter (SLC6A7)	DTH1GEL	SC6A7_HUMAN	Substrate	[4]
Proton-coupled amino acid transporter 4 (SLC36A4)	DTBS49U	S36A4_HUMAN	Substrate	[5]
Na(+)/Cl(-) betaine/GABA transporter (SLC6A12)	DTBPTJF	S6A12_HUMAN	Substrate	[6]
L-type amino acid transporter 2 (SLC7A8)	DTJF3DX	LAT2_HUMAN	Substrate	[7]
Proton-coupled amino acid transporter 1 (SLC36A1)	DT48WEM	S36A1_HUMAN	Substrate	[8]

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. (Ligand id: 3314).
• [2] Mechanistic insight into the role of transition-state stabilization in cyclophilin A. J Am Chem Soc. 2009 Jan 14;131(1):147-52.
• [3] Escherichia coli cyclophilin B binds a highly distorted form of trans-prolyl peptide isomer. Eur J Biochem. 2004 Sep;271(18):3794-803.
• [4] A new association between polymorphisms of the SLC6A7 gene in the chromosome 5q31-32 region and asthma. J Hum Genet. 2010 Jun;55(6):358-65.
• [5] SLC36A4 (hPAT4) is a high affinity amino acid transporter when expressed in Xenopus laevis oocytes. J Biol Chem. 2011 Jan 28;286(4):2455-60.
• [6] Interpreting metabolomic profiles using unbiased pathway models. PLoS Comput Biol. 2010 Feb 26;6(2):e1000692.
• [7] The Transporter Classification Database (TCDB): recent advances. Nucleic Acids Res. 2016 Jan 4;44(D1):D372-9. (ID: 2.A.3.8.20)
• [8] PAT1 (SLC36A1) shows nuclear localization and affects growth of smooth muscle cells from rats. Am J Physiol Endocrinol Metab. 2014 Jan 1;306(1):E65-74.
• [9] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [10] Structure-based design, synthesis, and biological evaluation of novel inhibitors of human cyclophilin A. J Med Chem. 2006 Feb 9;49(3):900-10.
• [11] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [12] Transport of amino acids and GABA analogues via the human proton-coupled amino acid transporter, hPAT1: characterization of conditions for affinity and transport experiments in Caco-2 cells. Eur J Pharm Sci. 2008 Sep 2;35(1-2):86-95.
• [13] Indirect regulation of the intestinal H+-coupled amino acid transporter hPAT1 (SLC36A1). J Cell Physiol. 2005 Aug;204(2):604-13.
• [14] Delta-aminolevulinic acid is a substrate for the amino acid transporter SLC36A1 (hPAT1). Br J Pharmacol. 2010 Mar;159(6):1339-53.
• [15] Intestinal gaboxadol absorption via PAT1 (SLC36A1): modified absorption in vivo following co-administration of L-tryptophan. Br J Pharmacol. 2009 Aug;157(8):1380-9.
• [16] Rectal absorption of vigabatrin, a substrate of the proton coupled amino acid transporter (PAT1, Slc36a1), in rats. Pharm Res. 2012 Apr;29(4):1134-42.
• [17] The Transporter Classification Database (TCDB): recent advances. Nucleic Acids Res. 2016 Jan 4;44(D1):D372-9. (ID: 2.A.22.3.1)
• [18] Deletion of the betaine-GABA transporter (BGT1; slc6a12) gene does not affect seizure thresholds of adult mice. Epilepsy Res. 2011 Jun;95(1-2):70-81.
• [19] Quantifying the relative contributions of different solute carriers to aggregate substrate transport. Sci Rep. 2017 Jan 16;7:40628.