Target Validation Information
TTD ID T89515
Target Name Polypeptide deformylase (PDF)
Type of Target
Successful
Drug Potency against Target Aminopterin Drug Info IC50 = 35 nM [22]
Chlorproguanil Drug Info IC50 = 8600 nM [18]
Proguanil Drug Info IC50 = 27000 nM [24]
Pyrimethamine Drug Info Ki = 0.2 nM [20]
Trimethoprim Drug Info IC50 = 8 nM [21]
Trimetrexate Drug Info IC50 = 10 nM [23]
Drug Info IC50 = 18 nM [5]
Drug Info IC50 = 220 nM [8]
2-Allylthio-3-benzyl-6-nitro-quinazolin-4(3H)-one Drug Info IC50 = 3000 nM [10]
2-Allylthio-6-amino-3-benzyl-quinazolin-4(3H)-one Drug Info IC50 = 8000 nM [10]
3-Benzyl-2-ethylthio-6-nitro-quinazolin-4(3H)-one Drug Info IC50 = 10000 nM [10]
3-benzyl-2-mercapto-6-nitroquinazolin-4(3H)-one Drug Info IC50 = 15000 nM [10]
3-Phenylsulfanylmethyl-quinoxaline-5,7-diamine Drug Info IC50 = 9500 nM [12]
4-(2,6-diamino-9H-purin-8-yl)-2,6-dimethoxyphenol Drug Info IC50 = 15300 nM [9]
5-((E)-Styryl)-quinazoline-2,4-diamine Drug Info IC50 = 1200 nM [13]
5-(2-fluorobenzyloxy)quinazoline-2,4-diamine Drug Info IC50 = 0.39 nM [6]
5-p-Tolylsulfanyl-quinazoline-2,4-diamine Drug Info IC50 = 23 nM [1]
5-Phenethyl-quinazoline-2,4-diamine Drug Info IC50 = 370 nM [13]
5-Phenylsulfanyl-2,4-Quinazolinediamine Drug Info IC50 = 34 nM [1]
6,7-Diphenyl-pteridine-2,4-diamine Drug Info IC50 = 240 nM [2]
6-(2-Phenylsulfanyl-ethyl)-pteridine-2,4-diamine Drug Info IC50 = 770 nM [2]
6-m-Tolyl-pteridine-2,4,7-triamine Drug Info IC50 = 18 nM [2]
6-Phenylaminomethyl-quinazoline-2,4-diamine Drug Info IC50 = 440 nM [3]
6-Phenylsulfanylmethyl-pteridine-2,4-diamine Drug Info IC50 = 770 nM [14]
7-Methyl-7H-pyrrolo[3,2-f]quinazoline-1,3-diamine Drug Info Ki = 25 nM [15]
7H-Pyrrolo[3,2-f]quinazoline-1,3-diamine Drug Info Ki = 23 nM [15]
8-(2,3,4-trimethoxyphenyl)-9H-purine-2,6-diamine Drug Info IC50 = 3700 nM [9]
8-(2,4,5-trimethoxyphenyl)-9H-purine-2,6-diamine Drug Info IC50 = 7000 nM [9]
8-(2,4,6-trimethoxyphenyl)-9H-purine-2,6-diamine Drug Info IC50 = 1880 nM [9]
8-(2,4-dimethoxyphenyl)-9H-purine-2,6-diamine Drug Info IC50 = 2400 nM [9]
8-(2,5-dimethoxyphenyl)-9H-purine-2,6-diamine Drug Info IC50 = 3500 nM [9]
8-(2,6-Dichloro-phenyl)-9H-purine-2,6-diamine Drug Info IC50 = 11000 nM [16]
8-(3,4,5-trimethoxyphenyl)-9H-purine-2,6-diamine Drug Info IC50 = 13000 nM [9]
8-(3,4-dichlorophenyl)-9H-purine-2,6-diamine Drug Info IC50 = 6700 nM [9]
8-(3,4-dimethoxyphenyl)-9H-purine-2,6-diamine Drug Info IC50 = 14200 nM [9]
8-(3,5-dimethoxyphenyl)-9H-purine-2,6-diamine Drug Info IC50 = 3000 nM [9]
8-benzyl-9H-purine-2,6-diamine Drug Info IC50 = 1600 nM [9]
8-Pyridin-4-yl-9H-purine-2,6-diamine Drug Info IC50 = 18000 nM [16]
GNF-PF-173 Drug Info IC50 = 34 nM [11]
GNF-PF-607 Drug Info IC50 = 84 nM [4]
N*6*-Benzyl-quinazoline-2,4,6-triamine Drug Info IC50 = 320 nM [4]
PIRITREXIM Drug Info IC50 = 4.4 nM [7]
PREMETREXED Drug Info IC50 = 2300 nM [17]
Action against Disease Model Meprobamate Drug Info The drug resistance profiles of Plasmodi uM falcipar uM isolated from four regions in Kenya were analyzed for drug resistance profiles. We observed variability in resistance to a broad range of antimalarial drugs across Kenya as determined from in vitro drug susceptibility screening and genotyping analysis.IC50: 54 ng/mL [19]
References
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REF 2 Further studies on 2,4-diamino-5-(2',5'-disubstituted benzyl)pyrimidines as potent and selective inhibitors of dihydrofolate reductases from three ... J Med Chem. 2003 Apr 24;46(9):1726-36.
REF 3 Design and synthesis of dihydrofolate reductase inhibitors encompassing a bridging ester group. Evaluation in a mouse colitis model. J Med Chem. 2003 Jul 31;46(16):3455-62.
REF 4 CoMFA and CoMSIA analyses of Pneumocystis carinii dihydrofolate reductase, Toxoplasma gondii dihydrofolate reductase, and rat liver dihydrofolate r... J Med Chem. 2005 Mar 10;48(5):1448-69.
REF 5 Synthesis of N-{4-[(2,4-diamino-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid and N-{4-[(2-amino-4-oxo-5-methy... J Med Chem. 2005 Nov 17;48(23):7215-22.
REF 6 Synthesis and biological evaluation of novel 2,4-diaminoquinazoline derivatives as SMN2 promoter activators for the potential treatment of spinal m... J Med Chem. 2008 Feb 14;51(3):449-69.
REF 7 N9-substituted 2,4-diaminoquinazolines: synthesis and biological evaluation of lipophilic inhibitors of pneumocystis carinii and toxoplasma gondii ... J Med Chem. 2008 Oct 9;51(19):6195-200.
REF 8 Design, synthesis, and X-ray crystal structure of classical and nonclassical 2-amino-4-oxo-5-substituted-6-ethylthieno[2,3-d]pyrimidines as dual th... J Med Chem. 2009 Aug 13;52(15):4892-902.
REF 9 CoMFA analysis of tgDHFR and rlDHFR based on antifolates with 6-5 fused ring system using the all-orientation search (AOS) routine and a modified c... Bioorg Med Chem. 2010 Feb 15;18(4):1684-701.
REF 10 Non-classical antifolates. Part 2: synthesis, biological evaluation, and molecular modeling study of some new 2,6-substituted-quinazolin-4-ones. Bioorg Med Chem. 2010 Apr 15;18(8):2849-63.
REF 11 Synthesis and biological evaluation of poly-gamma-glutamyl metabolites of 10-deazaaminopterin and 10-ethyl-10-deazaaminopterin. J Med Chem. 1988 Jan;31(1):181-5.
REF 12 New drug developments for opportunistic infections in immunosuppressed patients: Pneumocystis carinii. J Med Chem. 1995 Nov 24;38(24):4739-59.
REF 13 2,4-Diamino-5-substituted-quinazolines as inhibitors of a human dihydrofolate reductase with a site-directed mutation at position 22 and of the dih... J Med Chem. 1995 Mar 3;38(5):745-52.
REF 14 Nonclassical 2,4-diamino-8-deazafolate analogues as inhibitors of dihydrofolate reductases from rat liver, Pneumocystis carinii, and Toxoplasma gon... J Med Chem. 1996 Apr 26;39(9):1836-45.
REF 15 High-affinity inhibitors of dihydrofolate reductase: antimicrobial and anticancer activities of 7,8-dialkyl-1,3-diaminopyrrolo[3,2-f]quinazolines w... J Med Chem. 1996 Feb 16;39(4):892-903.
REF 16 Conformationally restricted analogues of trimethoprim: 2,6-diamino-8-substituted purines as potential dihydrofolate reductase inhibitors from Pneum... J Med Chem. 1997 Sep 12;40(19):3032-9.
REF 17 Synthesis, antifolate, and antitumor activities of classical and nonclassical 2-amino-4-oxo-5-substituted-pyrrolo[2,3-d]pyrimidines. J Med Chem. 2001 Jun 7;44(12):1993-2003.
REF 18 Biguanide-atovaquone synergy against Plasmodium falciparum in vitro. Antimicrob Agents Chemother. 2002 Aug;46(8):2700-3.
REF 19 Drug susceptibility and genetic evaluation of Plasmodium falciparum isolates obtained in four distinct geographical regions of Kenya. Antimicrob Agents Chemother. 2004 Sep;48(9):3598-601.
REF 20 Targeting DHFR in parasitic protozoa. Drug Discov Today. 2005 Jan 15;10(2):121-8.
REF 21 Isolation and expression of the Pneumocystis carinii dihydrofolate reductase gene. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8625-9.
REF 22 Methotrexate analogues. 26. Inhibition of dihydrofolate reductase and folylpolyglutamate synthetase activity and in vitro tumor cell growth by methotrexate and aminopterin analogues containing a basic amino acid side chain. J Med Chem. 1986 May;29(5):655-60.
REF 23 Lipophilic antifolates as agents against opportunistic infections. 1. Agents superior to trimetrexate and piritrexim against Toxoplasma gondii and Pneumocystis carinii in in vitro evaluations. J Med Chem. 1996 Mar 15;39(6):1271-80.
REF 24 Cycloguanil and its parent compound proguanil demonstrate distinct activities against Plasmodium falciparum malaria parasites transformed with human dihydrofolate reductase. Mol Pharmacol. 1998 Dec;54(6):1140-7.

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