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

General Information of Drug (ID: DMVOGT4)

• Drug Name: PREMETREXED Drug Info
• Synonyms: [3H]pemetrexed

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 394493
  TTD Drug ID: DMVOGT4

Molecule-Related Drug Atlas

Drug(s) Targeting Proton-coupled folate transporter (SLC46A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[4]
Folic acid	DMEMBJC	Folate-deficiency anemia	3A02.Y	Approved	[4]
[3H]N5-methylfolate	DM0THB9	Discovery agent	N.A.	Investigative	[4]
[3H]folinic acid	DME0XHN	Discovery agent	N.A.	Investigative	[4]

Drug(s) Targeting Candida Thymidylate synthase (Candi TMP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Ciprofloxacin XR	DM2NLS9	Bacterial infection	1A00-1C4Z	Approved	[6]
Pemetrexed	DMMX2E6	Malignant pleural mesothelioma	2C26.0	Approved	[7]
Trifluridine	DMG2YBD	Virus infection	1A24-1D9Z	Approved	[8]
Capecitabine	DMTS85L	Colorectal cancer	2B91.Z	Approved	[9]
Raltitrexed	DMT9K8G	Rectal adenocarcinoma	2B92	Approved	[10]
Floxuridine	DM04LR2	Colorectal cancer	2B91.Z	Approved	[11]
Leucovorin/5-fluorouracil	DMZT4N7	Colon cancer	2B90.Z	Approved	[12]
Flucytosine	DM13VTW	Endocarditis	BB40-BA42	Approved	[13]
Nolatrexed	DMOF0CA	Solid tumour/cancer	2A00-2F9Z	Phase 3	[14]

Drug(s) Targeting Polypeptide deformylase (PDF)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Proguanil	DMBL79I	Malaria	1F40-1F45	Approved	[15]
Meprobamate	DMHM93Y	Anxiety disorder	6B00-6B0Z	Approved	[16]
Pralatrexate	DMAO80I	Breast cancer	2C60-2C65	Approved	[17]
Ustekinumab	DMHTYK3	Plaque psoriasis	EA90.0	Approved	[18]
Trimetrexate	DMDEA85	Toxoplasmosis	1F57	Approved	[19]
MCB-3837	DM0R4Z5	Malaria	1F40-1F45	Approved	[16]
Chlorproguanil	DM1IFGT	Malaria	1F40-1F45	Approved	[16]
LY333531	DMGMC8H	Solid tumour/cancer	2A00-2F9Z	Phase 2	[20]
Metoprine	DM5GQD7	Advanced cancer	2A00-2F9Z	Phase 2	[21]
Aminopterin	DMQ9RBV	leukaemia	2A60-2B33	Withdrawn from market	[6]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Candida Thymidylate synthase (Candi TMP1)	TTU6BFZ	TYSY_CANAL	Inhibitor	[2]
Polypeptide deformylase (PDF)	TT9SL3Q	DEFM_HUMAN	Inhibitor	[3]
Proton-coupled folate transporter (SLC46A1)	TTY8Z2E	PCFT_HUMAN	Modulator	[4]

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: 6688).
• [2] Dual inhibitors of thymidylate synthase and dihydrofolate reductase as antitumor agents: design, synthesis, and biological evaluation of classical ... J Med Chem. 2006 Feb 9;49(3):1055-65.
• [3] Synthesis, antifolate, and antitumor activities of classical and nonclassical 2-amino-4-oxo-5-substituted-pyrrolo[2,3-d]pyrimidines. J Med Chem. 2001 Jun 7;44(12):1993-2003.
• [4] 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: 1213).
• [5] The efficacy of the combination therapy of 5-fluorouracil, cisplatin and leucovorin for hepatocellular carcinoma and its predictable factors. Cancer Chemother Pharmacol. 2004 Apr;53(4):296-304.
• [6] 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.
• [7] Updated clinical information on multitargeted antifolates in lung cancer. Clin Lung Cancer. 2009 Mar;10 Suppl 1:S35-40.
• [8] Trifluorothymidine induces cell death independently of p53. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):699-703.
• [9] UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin Cancer Res. 2005 Feb 1;11(3):1226-36.
• [10] DNA damage and homologous recombination signaling induced by thymidylate deprivation. Biochem Pharmacol. 2008 Oct 15;76(8):987-96.
• [11] Antisense down-regulation of thymidylate synthase to suppress growth and enhance cytotoxicity of 5-FUdR, 5-FU and Tomudex in HeLa cells. Br J Pharmacol. 1999 Aug;127(8):1777-86.
• [12] Decreased levels of UMP kinase as a mechanism of fluoropyrimidine resistance. Mol Cancer Ther. 2009 May;8(5):1037-44.
• [13] Antifungal agents: mode of action in yeast cells. Rev Esp Quimioter. 2006 Jun;19(2):130-9.
• [14] A phase I study of the lipophilic thymidylate synthase inhibitor Thymitaq (nolatrexed dihydrochloride) given by 10-day oral administration. Br J Cancer. 1999 Feb;79(5-6):915-20.
• [15] 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.
• [16] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [17] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [18] Novel Saccharomyces cerevisiae screen identifies WR99210 analogues that inhibit Mycobacterium tuberculosis dihydrofolate reductase. Antimicrob Agents Chemother. 2002 Nov;46(11):3362-9.
• [19] Expression and characterization of recombinant human-derived Pneumocystis carinii dihydrofolate reductase. Antimicrob Agents Chemother. 2000 Nov;44(11):3092-6.
• [20] 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.
• [21] Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.