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

General Information of Drug (ID: DM7Y60I)

• Drug Name: Plevitrexed Drug Info
• Synonyms: ZD 9331; ZD9331; 153537-73-6; Plevitrexed [INN]; ZD-9331; NSC 696259; UNII-L9P2881C3H; CHEMBL126648; (2s)-2-[(2-fluoro-4-{[(4-hydroxy-2,7-dimethylquinazolin-6-yl)methyl](prop-2-yn-1-yl)amino}benzoyl)amino]-4-(2h-tetrazol-5-yl)butanoic acid; L9P2881C3H; Plevitrexed (INN); 172521-94-7; (2S)-2-[[4-[(2,7-dimethyl-4-oxo-1H-quinazolin-6-yl)methyl-prop-2-ynylamino]-2-fluorobenzoyl]amino]-4-(2H-tetrazol-5-yl)butanoic acid; 1H-Tetrazole-5-butanoic acid,

Indication

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

• Cross-matching ID:
  PubChem CID: 135430970
  CAS Number: CAS 153537-73-6
  TTD Drug ID: DM7Y60I

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 (R)-isomer	DMTL39C	Gastric adenocarcinoma	2B72	Phase 2	[2]

Drug(s) Affected By Cell division control protein 45 homolog (CDC45)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[13]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[14]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[15]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[16]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[17]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[18]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[19]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[19]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[20]
Demecolcine	DMCZQGK	Solid tumour/cancer	2A00-2F9Z	Approved	[21]

Drug(s) Affected By Cyclin-dependent kinase inhibitor 1 (CDKN1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[22]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[23]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[24]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[25]
Talazoparib	DM1KS78	Breast cancer	2C60-2C65	Approved	[26]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[27]
Etretinate	DM2CZFA	Keratosis	ED56	Approved	[28]
Prednisone	DM2HG4X	Acute asthma	CA23	Approved	[29]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[30]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[31]

Drug(s) Affected By Cell division control protein 6 homolog (CDC6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[13]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[31]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[14]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[32]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[16]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[33]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[34]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[19]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[19]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[35]

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]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cell division control protein 45 homolog (CDC45)	OT6NNLOD	CDC45_HUMAN	Gene/Protein Processing	[3]
Cell division control protein 6 homolog (CDC6)	OTX93FE7	CDC6_HUMAN	Gene/Protein Processing	[3]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Gene/Protein Processing	[3]
Thymidylate synthase	OTXTG0C7	TYSY_HUMAN	Gene/Protein Processing	[3]

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: 8278).
• [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] P21Cip1 is a critical mediator of the cytotoxic action of thymidylate synthase inhibitors in colorectal carcinoma cells. Cancer Res. 2004 Sep 1;64(17):6296-303. doi: 10.1158/0008-5472.CAN-04-0863.
• [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] Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells. Toxicol Sci. 2023 Feb 17;191(2):227-238. doi: 10.1093/toxsci/kfac131.
• [14] Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells. Cancer Sci. 2007 Jun;98(6):890-9.
• [15] Quercetin potentiates apoptosis by inhibiting nuclear factor-kappaB signaling in H460 lung cancer cells. Biol Pharm Bull. 2013;36(6):944-51. doi: 10.1248/bpb.b12-01004.
• [16] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [17] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [18] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [19] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [20] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] Zidovudine induces S-phase arrest and cell cycle gene expression changes in human cells. Mutagenesis. 2005 Mar;20(2):139-46. doi: 10.1093/mutage/gei019. Epub 2005 Mar 22.
• [23] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [24] Gene expression profiles with activation of the estrogen receptor alpha-selective estrogen receptor modulator complex in breast cancer cells expressing wild-type estrogen receptor. Cancer Res. 2002 Aug 1;62(15):4419-26.
• [25] Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells. Toxicol Appl Pharmacol. 2017 Nov 15;335:16-27. doi: 10.1016/j.taap.2017.09.017. Epub 2017 Sep 21.
• [26] BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile. J Biochem Mol Toxicol. 2019 May;33(5):e22286. doi: 10.1002/jbt.22286. Epub 2019 Jan 23.
• [27] Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
• [28] Bexarotene activates the p53/p73 pathway in human cutaneous T-cell lymphoma. Br J Dermatol. 2009 Mar;160(3):519-26. doi: 10.1111/j.1365-2133.2008.08931.x. Epub 2008 Nov 25.
• [29] Glucocorticoids induce G1 arrest of lymphoblastic cells through retinoblastoma protein Rb1 dephosphorylation in childhood acute lymphoblastic leukemia in vivo. Cancer Biol Ther. 2004 May;3(5):470-6. doi: 10.4161/cbt.3.5.838. Epub 2004 May 9.
• [30] Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. Clin Cancer Res. 2000 Mar;6(3):891-900.
• [31] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
• [32] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [33] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [34] Activation of the p38 MAPK/Akt/ERK1/2 signal pathways is required for the protein stabilization of CDC6 and cyclin D1 in low-dose arsenite-induced cell proliferation. J Cell Biochem. 2010 Dec 15;111(6):1546-55. doi: 10.1002/jcb.22886.
• [35] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.