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

General Information of Drug (ID: DMAO80I)

• Drug Name: Pralatrexate Drug Info
• Synonyms: Folotyn (TN)

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[1]
Peripheral T-cell lymphoma	2A90.C	Approved	[1]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified		Approved	[2]

• Cross-matching ID:
  PubChem CID: 148121
  ChEBI ID: CHEBI:71223
  CAS Number: CAS 146464-95-1
  TTD Drug ID: DMAO80I
  VARIDT Drug ID: DR00041
  INTEDE Drug ID: DR1320
  ACDINA Drug ID: D01353

Molecule-Related Drug Atlas

Drug(s) Targeting Polypeptide deformylase (PDF)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Proguanil	DMBL79I	Malaria	1F40-1F45	Approved	[6]
Meprobamate	DMHM93Y	Anxiety		Approved	[7]
Ustekinumab	DMHTYK3	Plaque psoriasis	EA90.0	Approved	[8]
Trimetrexate	DMDEA85	Toxoplasmosis	1F57	Approved	[9]
MCB-3837	DM0R4Z5	Malaria	1F40-1F45	Approved	[7]
Chlorproguanil	DM1IFGT	Malaria	1F40-1F45	Approved	[7]
LY333531	DMGMC8H	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]
Metoprine	DM5GQD7	Advanced cancer	2A00-2F9Z	Phase 2	[11]
Aminopterin	DMQ9RBV	leukaemia	2A60-2B33	Withdrawn from market	[12]
2-Sulfhydryl-Ethanol	DMJBO3D	Discovery agent	N.A.	Investigative	[13]

Drug(s) Transported By Folate transporter 1 (SLC19A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[14]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[14]
Pemetrexed	DMMX2E6	Central nervous system lymphoma	2B33.5	Approved	[14]

Drug(s) Transported By Proton-coupled folate transporter (SLC46A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[15]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[16]
Pemetrexed	DMMX2E6	Central nervous system lymphoma	2B33.5	Approved	[17]

Drug(s) Metabolized By Folylpolyglutamate synthase (FPGS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[18]
DACTHF	DMCNAME	N. A.	N. A.	Investigative	[19]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Polypeptide deformylase (PDF)	TT9SL3Q	DEFM_HUMAN	Inhibitor	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Folate transporter 1 (SLC19A1)	DTOSN46	S19A1_HUMAN	Substrate	[4]
Proton-coupled folate transporter (SLC46A1)	DTDJEMI	PCFT_HUMAN	Substrate	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Folylpolyglutamate synthase (FPGS) Main DME	DECWT2V	FOLC_HUMAN	Substrate	[5]

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: 6840).
• [2] Pralatrexate FDA Label
• [3] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [4] Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance. Drug Resist Updat. 2012 Aug;15(4):183-210.
• [5] Pralatrexate : evaluation of clinical efficacy and toxicity in T-cell lymphoma. Expert Opin Pharmacother. 2013 Mar;14(4):515-23.
• [6] Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10931-6.
• [7] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [8] Novel Saccharomyces cerevisiae screen identifies WR99210 analogues that inhibit Mycobacterium tuberculosis dihydrofolate reductase. Antimicrob Agents Chemother. 2002 Nov;46(11):3362-9.
• [9] Expression and characterization of recombinant human-derived Pneumocystis carinii dihydrofolate reductase. Antimicrob Agents Chemother. 2000 Nov;44(11):3092-6.
• [10] Three-dimensional structure of M. tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs. J Mol Biol. 2000 Jan 14;295(2):307-23.
• [11] Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
• [12] Loss of folylpoly-gamma-glutamate synthetase activity is a dominant mechanism of resistance to polyglutamylation-dependent novel antifolates in multiple human leukemia sublines. Int J Cancer. 2003 Feb 20;103(5):587-99.
• [13] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [14] Biology of the major facilitative folate transporters SLC19A1 and SLC46A1. Curr Top Membr. 2014;73:175-204.
• [15] Site-specific contribution of proton-coupled folate transporter/haem carrier protein 1 in the intestinal absorption of methotrexate in rats. J Pharm Pharmacol. 2009 Jul;61(7):911-8.
• [16] Characterization of uptake of folates by rat and human blood-brain barrier endothelial cells. Biofactors. 2010 May-Jun;36(3):201-9.
• [17] The proton-coupled folate transporter: impact on pemetrexed transport and on antifolates activities compared with the reduced folate carrier. Mol Pharmacol. 2008 Sep;74(3):854-62.
• [18] The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4.
• [19] Role of folylpolyglutamate synthetase in the metabolism and cytotoxicity of 5-deazaacyclotetrahydrofolate, an anti-purine drug. J Biol Chem. 1994 Apr 1;269(13):9714-20.