Details of the Drug

General Information of Drug (ID: DM6GWAC)

Drug Name
DDATHF
Synonyms
DATHF; 95693-76-8; 5,10-dideazatetrahydrofolate; 5,10-Dideaza-5,6,7,8-tetrahydrofolic acid; 5,10-dideazatetrahydrofolic acid; L-Glutamic acid,N-[4-[2-(2-amino-3,4,5,6,7,8-hexahydro-4-oxopyrido[2,3-d]pyrimidin-6-yl)ethyl]benzoyl]-; L-Glutamic acid, N-(4-(2-(2-amino-1,4,5,6,7,8-hexahydro-4-oxopyrido(2,3-d)pyrimidin-6-yl)ethyl)benzoyl)-; C21H25N5O6; AC1L2XXH; Pyrido(2,3-d)pyrimidine, L-glutamic acid deriv; CHEMBL142806; SCHEMBL9045915; ZUQBAQVRAURMCL-CVRLYYSRSA-N; 5,10-Dideazatetrahydrofolic Acid
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 443.5
Topological Polar Surface Area (xlogp) 0.3
Rotatable Bond Count (rotbonds) 9
Hydrogen Bond Donor Count (hbonddonor) 6
Hydrogen Bond Acceptor Count (hbondacc) 8
Chemical Identifiers
Formula
C21H25N5O6
IUPAC Name
2-[[4-[2-(2-amino-4-oxo-5,6,7,8-tetrahydro-3H-pyrido[2,3-d]pyrimidin-6-yl)ethyl]benzoyl]amino]pentanedioic acid
Canonical SMILES
C1C(CNC2=C1C(=O)NC(=N2)N)CCC3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O
InChI
InChI=1S/C21H25N5O6/c22-21-25-17-14(19(30)26-21)9-12(10-23-17)2-1-11-3-5-13(6-4-11)18(29)24-15(20(31)32)7-8-16(27)28/h3-6,12,15H,1-2,7-10H2,(H,24,29)(H,27,28)(H,31,32)(H4,22,23,25,26,30)
InChIKey
ZUQBAQVRAURMCL-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
135436405
TTD ID
D06YIB

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
GAR transformylase (GART) TTCSJBZ PUR2_HUMAN Modulator [2]
Polypeptide deformylase (PDF) TT9SL3Q DEFM_HUMAN Inhibitor [1]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Discovery agent
ICD Disease Classification N.A.
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Polypeptide deformylase (PDF) DTT PDF 8.87E-16 -0.54 -0.86
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
2 Rational design, synthesis, evaluation, and crystal structure of a potent inhibitor of human GAR Tfase: 10-(trifluoroacetyl)-5,10-dideazaacyclic-5,... Biochemistry. 2003 May 27;42(20):6043-56.
3 Phase I study of AG2034, a targeted GARFT inhibitor, administered once every 3 weeks. Cancer Chemother Pharmacol. 2000;45(5):423-7.
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 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.