Details of the Drug

General Information of Drug (ID: DMQ9RBV)

• Drug Name: Aminopterin
• 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leukaemia	2A60-2B33	Withdrawn from market	[1]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
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 440.4
  Logarithm of the Partition Coefficient (xlogp); -2
  Rotatable Bond Count (rotbonds); 9
  Hydrogen Bond Donor Count (hbonddonor); 6
  Hydrogen Bond Acceptor Count (hbondacc); 12
• Chemical Identifiers:
  Formula: C19H20N8O5
  IUPAC Name: (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid
  Canonical SMILES: C1=CC(=CC=C1C(=O)N[C@@H](CCC(=O)O)C(=O)O)NCC2=CN=C3C(=N2)C(=NC(=N3)N)N
  InChI: InChI=1S/C19H20N8O5/c20-15-14-16(27-19(21)26-15)23-8-11(24-14)7-22-10-3-1-9(2-4-10)17(30)25-12(18(31)32)5-6-13(28)29/h1-4,8,12,22H,5-7H2,(H,25,30)(H,28,29)(H,31,32)(H4,20,21,23,26,27)/t12-/m0/s1
  InChIKey: TVZGACDUOSZQKY-LBPRGKRZSA-N
• Cross-matching ID:
  PubChem CID: 169371
  ChEBI ID: CHEBI:22526
  CAS Number: 54-62-6
  DrugBank ID: DB08878
  TTD ID: D0D2RN

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]

Molecular Expression Atlas of This Drug

• The Studied Disease: leukaemia
• ICD Disease Classification: 2A60-2B33

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Polypeptide deformylase (PDF)	DTT	PDF	8.87E-16	-0.54	-0.86

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.