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

General Information of Drug (ID: DMCEM0L)

• Drug Name: AG-331 Drug Info
• Synonyms: Metesind glucuronate

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 3047716
  CAS Number: CAS 138384-68-6
  TTD Drug ID: DMCEM0L

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	[3]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[4]
Pemetrexed	DMMX2E6	Central nervous system lymphoma	2B33.5	Approved	[5]
Trifluridine	DMG2YBD	Herpetic keratitis	1F00.10	Approved	[6]
Capecitabine	DMTS85L	Adenocarcinoma	2D40	Approved	[7]
Raltitrexed	DMT9K8G	Rectal adenocarcinoma	2B92	Approved	[8]
Floxuridine	DM04LR2	Colorectal cancer	2B91.Z	Approved	[9]
Flucytosine	DM13VTW	Cryptococcal meningitis		Approved	[10]
Nolatrexed	DMOF0CA	Solid tumour/cancer	2A00-2F9Z	Phase 3	[11]
Plevitrexed (R)-isomer	DMTL39C	Gastric adenocarcinoma	2B72	Phase 2	[12]

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]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003304)
• [2] Phase I trial of the thymidylate synthase inhibitor AG331 as a 5-day continuous infusion. Clin Cancer Res. 1996 Oct;2(10):1685-92.
• [3] 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.
• [4] 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.
• [5] Updated clinical information on multitargeted antifolates in lung cancer. Clin Lung Cancer. 2009 Mar;10 Suppl 1:S35-40.
• [6] Trifluorothymidine induces cell death independently of p53. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):699-703.
• [7] 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.
• [8] DNA damage and homologous recombination signaling induced by thymidylate deprivation. Biochem Pharmacol. 2008 Oct 15;76(8):987-96.
• [9] 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.
• [10] Antifungal agents: mode of action in yeast cells. Rev Esp Quimioter. 2006 Jun;19(2):130-9.
• [11] 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.
• [12] Cooperative inhibition of human thymidylate synthase by mixtures of active site binding and allosteric inhibitors. Biochemistry. 2007 Mar 13;46(10):2823-30.