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

General Information of Drug (ID: DMQ9RBV)

• Drug Name: Aminopterin Drug Info
• Synonyms: APGA; Aminopteridine; Aminopterine; Aminopterinum; Aminotrexate; Pteramina; Pteramina [Czech]; A 1784; A-7170;A-Ninopterin; ENT-26079; Kyselina 4-aminolistova; Kyselina 4-aminolistova [Czech]; Kyselina 4-aminopteroylglutamova; Kyselina 4-aminopteroylglutamova [Czech]; L-Glutamic acid, N-[4-[[(2,4-diamino-6-pteridinyl)methyl]amino]benzoyl]; N-(1-((2,4-Diamino-6-pteridinylmethyl)amino)benzoyl)glutaminsaeure; N-[(4-{[(2,4-diaminopteridin-6-yl)methyl]amino}phenyl)carbonyl]glutamic acid; N-(4-{[(2,4-diaminopteridin-6-yl)methyl]amino}benzoyl)-L-glutamic acid; N-(4-(((2,4-Diamino-6-pteridinyl)methyl)amino)benzoyl)-L-glutamic acid; Kyselina N-(p-((2,4-diamino-6-pteridinyl)methyl)benzoyl)-L(+)-glutamova; Kyselina N-(p-((2,4-diamino-6-pteridinyl)methyl)benzoyl)-L(+)-glutamova [Czech]; Kyselina N-(p-((2,4-diamino-6-pteridinylmethyl)amino)benzoyl)-L(+)-glutamova; Kyselina N-(p-((2,4-diamino-6-pteridinylmethyl)amino)benzoyl)-L(+)-glutamova [Czech]; N-(4-(((2,4-Diamino-6-pteridyl)-methyl)amino)benzoyl)-L-glutamic acid; (2R)-2-[[4-[(2,4-diaminopteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid; (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid; 2-[[4-[(2,4-diaminopteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid; 4'-Amino-folsaeure; 4'-Desoxy-4'-aminofolsaeure; 4-Amino pteroylglutamic acid; 4-Amino-4-deoxypteroylglutamate; 4-Amino-4-desoxy-pteroylglutaminsaeure; 4-Amino-PGA; 4-Aminofolic acid; 4-Aminopteroyl-<R>glutamic acid; 4-Aminopteroyl-L-glutamic acid; 4-Aminopteroyl-glutamic acid; 4-Aminopteroylglutamic acid

Indication

Disease Entry	ICD 11	Status	REF
leukaemia	2A60-2B33	Withdrawn from market	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 169371
  ChEBI ID: CHEBI:22526
  CAS Number: CAS 54-62-6
  TTD Drug ID: DMQ9RBV

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	[4]
Meprobamate	DMHM93Y	Anxiety		Approved	[5]
Pralatrexate	DMAO80I	Breast cancer	2C60-2C65	Approved	[6]
Ustekinumab	DMHTYK3	Plaque psoriasis	EA90.0	Approved	[7]
Trimetrexate	DMDEA85	Toxoplasmosis	1F57	Approved	[8]
MCB-3837	DM0R4Z5	Malaria	1F40-1F45	Approved	[5]
Chlorproguanil	DM1IFGT	Malaria	1F40-1F45	Approved	[5]
LY333531	DMGMC8H	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
Metoprine	DM5GQD7	Advanced cancer	2A00-2F9Z	Phase 2	[10]
2-Sulfhydryl-Ethanol	DMJBO3D	Discovery agent	N.A.	Investigative	[11]

Drug(s) Affected By Cellular tumor antigen p53 (TP53)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[12]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[13]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[14]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[16]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[17]
Floxuridine	DM04LR2	Colorectal cancer	2B91.Z	Approved	[18]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[19]
Mechlorethamine	DM0CVXA	Chronic myelogenous leukaemia	2A20.0	Approved	[20]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[21]

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	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Gene/Protein Processing	[3]

References

• [1] Drug information of Aminopterin, Health Canada, 2007.
• [2] 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.
• [3] Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
• [4] 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.
• [5] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [6] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [7] Novel Saccharomyces cerevisiae screen identifies WR99210 analogues that inhibit Mycobacterium tuberculosis dihydrofolate reductase. Antimicrob Agents Chemother. 2002 Nov;46(11):3362-9.
• [8] Expression and characterization of recombinant human-derived Pneumocystis carinii dihydrofolate reductase. Antimicrob Agents Chemother. 2000 Nov;44(11):3092-6.
• [9] 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.
• [10] Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
• [11] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [12] p53-R175H mutant gains new function in regulation of doxorubicin-induced apoptosis. Int J Cancer. 2005 Apr 10;114(3):331-6. doi: 10.1002/ijc.20818.
• [13] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [14] Azidothymidine and cisplatin increase p14ARF expression in OVCAR-3 ovarian cancer cell line. Toxicol Appl Pharmacol. 2006 Oct 1;216(1):89-97. doi: 10.1016/j.taap.2006.04.015. Epub 2006 May 19.
• [15] Quantitative analysis of gene expression changes in response to genotoxic compounds. Toxicol In Vitro. 2017 Mar;39:15-28. doi: 10.1016/j.tiv.2016.11.004. Epub 2016 Nov 5.
• [16] Induction of apoptosis by cidofovir in human papillomavirus (HPV)-positive cells. Oncol Res. 2000;12(9-10):397-408. doi: 10.3727/096504001108747855.
• [17] Gallic acid potentiates the apoptotic effect of paclitaxel and carboplatin via overexpression of Bax and P53 on the MCF-7 human breast cancer cell line. J Biochem Mol Toxicol. 2021 Feb;35(2):e22638. doi: 10.1002/jbt.22638. Epub 2020 Oct 1.
• [18] Regulation of human dUTPase gene expression and p53-mediated transcriptional repression in response to oxaliplatin-induced DNA damage. Nucleic Acids Res. 2009 Jan;37(1):78-95. doi: 10.1093/nar/gkn910. Epub 2008 Nov 16.
• [19] Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells. Oncotarget. 2019 Jan 1;10(1):45-59. doi: 10.18632/oncotarget.26534. eCollection 2019 Jan 1.
• [20] Nitrogen Mustard Alkylates and Cross-Links p53 in Human Keratinocytes. Chem Res Toxicol. 2022 Apr 18;35(4):636-650. doi: 10.1021/acs.chemrestox.1c00420. Epub 2022 Mar 21.
• [21] Fulvestrant induces resistance by modulating GPER and CDK6 expression: implication of methyltransferases, deacetylases and the hSWI/SNF chromatin remodelling complex. Br J Cancer. 2013 Nov 12;109(10):2751-62. doi: 10.1038/bjc.2013.583. Epub 2013 Oct 29.