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

General Information of Drug (ID: DMTL39C)

• Drug Name: Plevitrexed (R)-isomer Drug Info
• Synonyms: YW3548

Indication

Disease Entry	ICD 11	Status	REF
Gastric adenocarcinoma	2B72	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 213022
  TTD Drug ID: DMTL39C

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[4]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[5]
Pemetrexed	DMMX2E6	Central nervous system lymphoma	2B33.5	Approved	[6]
Trifluridine	DMG2YBD	Herpetic keratitis	1F00.10	Approved	[7]
Capecitabine	DMTS85L	Adenocarcinoma	2D40	Approved	[8]
Raltitrexed	DMT9K8G	Rectal adenocarcinoma	2B92	Approved	[9]
Floxuridine	DM04LR2	Colorectal cancer	2B91.Z	Approved	[10]
Flucytosine	DM13VTW	Cryptococcal meningitis		Approved	[11]
Nolatrexed	DMOF0CA	Solid tumour/cancer	2A00-2F9Z	Phase 3	[12]
Plevitrexed	DM7Y60I	Gastric adenocarcinoma	2B72	Phase 2	[2]

Drug(s) Targeting Thymidylate synthase (TYMS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NUC-3373	DMQ0F5P	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]
ICI-198583	DMW4L3K	Discovery agent	N.A.	Investigative	[14]

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]
Thymidylate synthase (TYMS)	TT5FOMZ	TYSY_HUMAN	Inhibitor	[3]

References

• [1] Clinical pipeline report, company report or official report of plevitrexed.
• [2] Cooperative inhibition of human thymidylate synthase by mixtures of active site binding and allosteric inhibitors. Biochemistry. 2007 Mar 13;46(10):2823-30.
• [3] Differential effect of 1,10-phenanthroline on mammalian, yeast, and parasite glycosylphosphatidylinositol anchor synthesis. Biochem Biophys Res Commun. 2001 Nov 16;288(5):1112-8.
• [4] 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.
• [5] 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.
• [6] Updated clinical information on multitargeted antifolates in lung cancer. Clin Lung Cancer. 2009 Mar;10 Suppl 1:S35-40.
• [7] Trifluorothymidine induces cell death independently of p53. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):699-703.
• [8] 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.
• [9] DNA damage and homologous recombination signaling induced by thymidylate deprivation. Biochem Pharmacol. 2008 Oct 15;76(8):987-96.
• [10] 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.
• [11] Antifungal agents: mode of action in yeast cells. Rev Esp Quimioter. 2006 Jun;19(2):130-9.
• [12] 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.
• [13] Clinical pipeline report, company report or official report of NuCana.
• [14] The biochemical pharmacology of the thymidylate synthase inhibitor, 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583). Biochem Pharmacol. 1991 Oct 24;42(10):1885-95.