Details of the Drug

General Information of Drug (ID: DM5GQD7)

• Drug Name: Metoprine
• Synonyms: METOPRINE; Methodichlorophen; DDMP; 7761-45-7; Metoprine [USAN]; BW-197U; TCMDC-123931; NSC-19494; SK 5265; 5-(3,4-DICHLOROPHENYL)-6-METHYLPYRIMIDINE-2,4-DIAMINE; U 197; NSC7364; U-197; UNII-2L9RKX796Q; Metoprine (USAN); BW 50-197; METOPRINE, METHODICHLOROPHEN; 5-(3,4-Dichlorophenyl)-6-methyl-2,4-pyrimidinediamine; NSC 7364; 2,4-Pyrimidinediamine, 5-(3,4-dichlorophenyl)-6-methyl-; NSC 19494; BW50197; BRN 0223622; 5-(3,4-Dichlorphenyl)-6-methyl-2,4-pyrimidindiamin; 2,4-Diamino-5-(3,4-dichlorophenyl)-6-methylpyrimidine; MLS002701892; DDMP; BW 197 U; BW 1970; BW 197U; BW 50197; BW 50,197; 2,4-Diamino-5-(3',4'-dichlorophenyl)-6-methyl pyrimidine; Chloroaniline 1

Indication

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Phase 2	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 269.13
  Topological Polar Surface Area (xlogp); 2.8
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 4
• Chemical Identifiers:
  Formula: C11H10Cl2N4
  IUPAC Name: 5-(3,4-dichlorophenyl)-6-methylpyrimidine-2,4-diamine
  Canonical SMILES: CC1=C(C(=NC(=N1)N)N)C2=CC(=C(C=C2)Cl)Cl
  InChI: InChI=1S/C11H10Cl2N4/c1-5-9(10(14)17-11(15)16-5)6-2-3-7(12)8(13)4-6/h2-4H,1H3,(H4,14,15,16,17)
  InChIKey: VQJHOPSWBGJHQS-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 24466
  CAS Number: 7761-45-7
  DrugBank ID: DB04655
  TTD ID: D02AIM

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Histamine N-methyltransferase (HNMT)	TT2B6EV	HNMT_HUMAN	Inhibitor	[3]
Polypeptide deformylase (PDF)	TT9SL3Q	DEFM_HUMAN	Inhibitor	[4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Advanced cancer
• ICD Disease Classification: 2A00-2F9Z

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] 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: 7412).
• [2] ClinicalTrials.gov (NCT01579110) Efficacy and Safety of Levamisole Combined With Standard Prednisolone in Warm Antibody Autoimmune Hemolytic Anemia.. U.S. National Institutes of Health.
• [3] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [4] Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
• [5] Effect of amodiaquine, a histamine N-methyltransferase inhibitor, on, Propionibacterium acnes and lipopolysaccharide-induced hepatitis in mice. Eur J Pharmacol. 2007 Mar 8;558(1-3):179-84.
• [6] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [7] 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.
• [8] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [9] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [10] Novel Saccharomyces cerevisiae screen identifies WR99210 analogues that inhibit Mycobacterium tuberculosis dihydrofolate reductase. Antimicrob Agents Chemother. 2002 Nov;46(11):3362-9.
• [11] Expression and characterization of recombinant human-derived Pneumocystis carinii dihydrofolate reductase. Antimicrob Agents Chemother. 2000 Nov;44(11):3092-6.
• [12] 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.
• [13] 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.