Target Validation Information
Target ID T89515
Target Name Dihydrofolate reductase
Target Type
Successful
Drug Potency against Target Trimetrexate Drug Info IC50 = 10 nM [553227]
Chlorproguanil Drug Info IC50 = 8600 nM [552301]
8-(3,4,5-trimethoxyphenyl)-9H-purine-2,6-diamine Drug Info IC50 = 13000 nM [530674]
8-(2,5-dimethoxyphenyl)-9H-purine-2,6-diamine Drug Info IC50 = 3500 nM [530674]
8-(3,4-dimethoxyphenyl)-9H-purine-2,6-diamine Drug Info IC50 = 14200 nM [530674]
8-(2,3,4-trimethoxyphenyl)-9H-purine-2,6-diamine Drug Info IC50 = 3700 nM [530674]
8-(3,4-dichlorophenyl)-9H-purine-2,6-diamine Drug Info IC50 = 6700 nM [530674]
4-(2,6-diamino-9H-purin-8-yl)-2,6-dimethoxyphenol Drug Info IC50 = 15300 nM [530674]
8-(2,4-dimethoxyphenyl)-9H-purine-2,6-diamine Drug Info IC50 = 2400 nM [530674]
2-Allylthio-3-benzyl-6-nitro-quinazolin-4(3H)-one Drug Info IC50 = 3000 nM [530816]
5-(2-fluorobenzyloxy)quinazoline-2,4-diamine Drug Info IC50 = 0.39 nM [529261]
PREMETREXED Drug Info IC50 = 2300 nM [535186]
Pyrimethamine Drug Info Ki = 0.2 nM [552496]
GNF-PF-173 Drug Info IC50 = 34 nM [532648]
8-(2,4,5-trimethoxyphenyl)-9H-purine-2,6-diamine Drug Info IC50 = 7000 nM [530674]
Proguanil Drug Info IC50 = 27000 nM [553287]
6-Phenylsulfanylmethyl-pteridine-2,4-diamine Drug Info IC50 = 770 nM [534121]
PDDF Drug Info IC50 = 18 nM [527854]
3-Benzyl-2-ethylthio-6-nitro-quinazolin-4(3H)-one Drug Info IC50 = 10000 nM [530816]
2-Allylthio-6-amino-3-benzyl-quinazolin-4(3H)-one Drug Info IC50 = 8000 nM [530816]
3-benzyl-2-mercapto-6-nitroquinazolin-4(3H)-one Drug Info IC50 = 15000 nM [530816]
5-p-Tolylsulfanyl-quinazoline-2,4-diamine Drug Info IC50 = 23 nM [526126]
5-((E)-Styryl)-quinazoline-2,4-diamine Drug Info IC50 = 1200 nM [533781]
GNF-PF-607 Drug Info IC50 = 84 nM [527455]
N*6*-Benzyl-quinazoline-2,4,6-triamine Drug Info IC50 = 320 nM [527455]
PIRITREXIM Drug Info IC50 = 4.4 nM [529669]
8-(3,5-dimethoxyphenyl)-9H-purine-2,6-diamine Drug Info IC50 = 3000 nM [530674]
8-benzyl-9H-purine-2,6-diamine Drug Info IC50 = 1600 nM [530674]
8-(2,4,6-trimethoxyphenyl)-9H-purine-2,6-diamine Drug Info IC50 = 1880 nM [530674]
8-(2,6-Dichloro-phenyl)-9H-purine-2,6-diamine Drug Info IC50 = 11000 nM [534468]
8-Pyridin-4-yl-9H-purine-2,6-diamine Drug Info IC50 = 18000 nM [534468]
Aminopterin Drug Info IC50 = 35 nM [553128]
5-Phenethyl-quinazoline-2,4-diamine Drug Info IC50 = 370 nM [533781]
6-m-Tolyl-pteridine-2,4,7-triamine Drug Info IC50 = 18 nM [526601]
6,7-Diphenyl-pteridine-2,4-diamine Drug Info IC50 = 240 nM [526601]
3-Phenylsulfanylmethyl-quinoxaline-5,7-diamine Drug Info IC50 = 9500 nM [533598]
5-Phenylsulfanyl-quinazoline-2,4-diamine Drug Info IC50 = 34 nM [526126]
CB-3717 Drug Info IC50 = 220 nM [530351]
6-(2-Phenylsulfanyl-ethyl)-pteridine-2,4-diamine Drug Info IC50 = 770 nM [526601]
6-Phenylaminomethyl-quinazoline-2,4-diamine Drug Info IC50 = 440 nM [526679]
7H-Pyrrolo[3,2-f]quinazoline-1,3-diamine Drug Info Ki = 23 nM [534126]
Trimethoprim Drug Info IC50 = 8 nM [553123]
7-Methyl-7H-pyrrolo[3,2-f]quinazoline-1,3-diamine Drug Info Ki = 25 nM [534126]
Action against Disease Model Meprobamate 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 [552454] Drug Info
References
Ref 553227Lipophilic 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 552454Drug 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 552301Biguanide-atovaquone synergy against Plasmodium falciparum in vitro. Antimicrob Agents Chemother. 2002 Aug;46(8):2700-3.
Ref 530674Bioorg Med Chem. 2010 Feb 15;18(4):1684-701. Epub 2010 Jan 6.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 cross-validated r(2)-guided region selection (q(2)-GRS) routine and its initial application.
Ref 530674Bioorg Med Chem. 2010 Feb 15;18(4):1684-701. Epub 2010 Jan 6.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 cross-validated r(2)-guided region selection (q(2)-GRS) routine and its initial application.
Ref 530674Bioorg Med Chem. 2010 Feb 15;18(4):1684-701. Epub 2010 Jan 6.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 cross-validated r(2)-guided region selection (q(2)-GRS) routine and its initial application.
Ref 530674Bioorg Med Chem. 2010 Feb 15;18(4):1684-701. Epub 2010 Jan 6.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 cross-validated r(2)-guided region selection (q(2)-GRS) routine and its initial application.
Ref 530674Bioorg Med Chem. 2010 Feb 15;18(4):1684-701. Epub 2010 Jan 6.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 cross-validated r(2)-guided region selection (q(2)-GRS) routine and its initial application.
Ref 530674Bioorg Med Chem. 2010 Feb 15;18(4):1684-701. Epub 2010 Jan 6.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 cross-validated r(2)-guided region selection (q(2)-GRS) routine and its initial application.
Ref 530674Bioorg Med Chem. 2010 Feb 15;18(4):1684-701. Epub 2010 Jan 6.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 cross-validated r(2)-guided region selection (q(2)-GRS) routine and its initial application.
Ref 530816Bioorg Med Chem. 2010 Apr 15;18(8):2849-63. Epub 2010 Mar 12.Non-classical antifolates. Part 2: synthesis, biological evaluation, and molecular modeling study of some new 2,6-substituted-quinazolin-4-ones.
Ref 529261J Med Chem. 2008 Feb 14;51(3):449-69. Epub 2008 Jan 19.Synthesis and biological evaluation of novel 2,4-diaminoquinazoline derivatives as SMN2 promoter activators for the potential treatment of spinal muscular atrophy.
Ref 535186Synthesis, 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 552496Targeting DHFR in parasitic protozoa. Drug Discov Today. 2005 Jan 15;10(2):121-8.
Ref 532648J Med Chem. 1988 Jan;31(1):181-5.Synthesis and biological evaluation of poly-gamma-glutamyl metabolites of 10-deazaaminopterin and 10-ethyl-10-deazaaminopterin.
Ref 530674Bioorg Med Chem. 2010 Feb 15;18(4):1684-701. Epub 2010 Jan 6.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 cross-validated r(2)-guided region selection (q(2)-GRS) routine and its initial application.
Ref 553287Cycloguanil 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.
Ref 534121J Med Chem. 1996 Apr 26;39(9):1836-45.Nonclassical 2,4-diamino-8-deazafolate analogues as inhibitors of dihydrofolate reductases from rat liver, Pneumocystis carinii, and Toxoplasma gondii.
Ref 527854J Med Chem. 2005 Nov 17;48(23):7215-22.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-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid as dual inhibitors of dihydrofolate reductase and thymidylate synthase and as potential antitumor agents.
Ref 530816Bioorg Med Chem. 2010 Apr 15;18(8):2849-63. Epub 2010 Mar 12.Non-classical antifolates. Part 2: synthesis, biological evaluation, and molecular modeling study of some new 2,6-substituted-quinazolin-4-ones.
Ref 530816Bioorg Med Chem. 2010 Apr 15;18(8):2849-63. Epub 2010 Mar 12.Non-classical antifolates. Part 2: synthesis, biological evaluation, and molecular modeling study of some new 2,6-substituted-quinazolin-4-ones.
Ref 530816Bioorg Med Chem. 2010 Apr 15;18(8):2849-63. Epub 2010 Mar 12.Non-classical antifolates. Part 2: synthesis, biological evaluation, and molecular modeling study of some new 2,6-substituted-quinazolin-4-ones.
Ref 526126J Med Chem. 2001 Aug 30;44(18):2928-32.X-Ray crystal structures of Candida albicans dihydrofolate reductase: high resolution ternary complexes in which the dihydronicotinamide moiety of NADPH is displaced by an inhibitor.
Ref 533781J Med Chem. 1995 Mar 3;38(5):745-52.2,4-Diamino-5-substituted-quinazolines as inhibitors of a human dihydrofolate reductase with a site-directed mutation at position 22 and of the dihydrofolate reductases from Pneumocystis carinii and Toxoplasma gondii.
Ref 527455J Med Chem. 2005 Mar 10;48(5):1448-69.CoMFA and CoMSIA analyses of Pneumocystis carinii dihydrofolate reductase, Toxoplasma gondii dihydrofolate reductase, and rat liver dihydrofolate reductase.
Ref 527455J Med Chem. 2005 Mar 10;48(5):1448-69.CoMFA and CoMSIA analyses of Pneumocystis carinii dihydrofolate reductase, Toxoplasma gondii dihydrofolate reductase, and rat liver dihydrofolate reductase.
Ref 529669J Med Chem. 2008 Oct 9;51(19):6195-200. Epub 2008 Sep 5.N9-substituted 2,4-diaminoquinazolines: synthesis and biological evaluation of lipophilic inhibitors of pneumocystis carinii and toxoplasma gondii dihydrofolate reductase.
Ref 530674Bioorg Med Chem. 2010 Feb 15;18(4):1684-701. Epub 2010 Jan 6.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 cross-validated r(2)-guided region selection (q(2)-GRS) routine and its initial application.
Ref 530674Bioorg Med Chem. 2010 Feb 15;18(4):1684-701. Epub 2010 Jan 6.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 cross-validated r(2)-guided region selection (q(2)-GRS) routine and its initial application.
Ref 530674Bioorg Med Chem. 2010 Feb 15;18(4):1684-701. Epub 2010 Jan 6.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 cross-validated r(2)-guided region selection (q(2)-GRS) routine and its initial application.
Ref 534468J Med Chem. 1997 Sep 12;40(19):3032-9.Conformationally restricted analogues of trimethoprim: 2,6-diamino-8-substituted purines as potential dihydrofolate reductase inhibitors from Pneumocystis carinii and Toxoplasma gondii.
Ref 534468J Med Chem. 1997 Sep 12;40(19):3032-9.Conformationally restricted analogues of trimethoprim: 2,6-diamino-8-substituted purines as potential dihydrofolate reductase inhibitors from Pneumocystis carinii and Toxoplasma gondii.
Ref 553128Methotrexate 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 533781J Med Chem. 1995 Mar 3;38(5):745-52.2,4-Diamino-5-substituted-quinazolines as inhibitors of a human dihydrofolate reductase with a site-directed mutation at position 22 and of the dihydrofolate reductases from Pneumocystis carinii and Toxoplasma gondii.
Ref 526601J Med Chem. 2003 Apr 24;46(9):1726-36.Further studies on 2,4-diamino-5-(2',5'-disubstituted benzyl)pyrimidines as potent and selective inhibitors of dihydrofolate reductases from three major opportunistic pathogens of AIDS.
Ref 526601J Med Chem. 2003 Apr 24;46(9):1726-36.Further studies on 2,4-diamino-5-(2',5'-disubstituted benzyl)pyrimidines as potent and selective inhibitors of dihydrofolate reductases from three major opportunistic pathogens of AIDS.
Ref 533598J Med Chem. 1995 Nov 24;38(24):4739-59.New drug developments for opportunistic infections in immunosuppressed patients: Pneumocystis carinii.
Ref 526126J Med Chem. 2001 Aug 30;44(18):2928-32.X-Ray crystal structures of Candida albicans dihydrofolate reductase: high resolution ternary complexes in which the dihydronicotinamide moiety of NADPH is displaced by an inhibitor.
Ref 530351J Med Chem. 2009 Aug 13;52(15):4892-902.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 thymidylate synthase and dihydrofolate reductase inhibitors and as potential antitumor agents.
Ref 526601J Med Chem. 2003 Apr 24;46(9):1726-36.Further studies on 2,4-diamino-5-(2',5'-disubstituted benzyl)pyrimidines as potent and selective inhibitors of dihydrofolate reductases from three major opportunistic pathogens of AIDS.
Ref 526679J Med Chem. 2003 Jul 31;46(16):3455-62.Design and synthesis of dihydrofolate reductase inhibitors encompassing a bridging ester group. Evaluation in a mouse colitis model.
Ref 534126J Med Chem. 1996 Feb 16;39(4):892-903.High-affinity inhibitors of dihydrofolate reductase: antimicrobial and anticancer activities of 7,8-dialkyl-1,3-diaminopyrrolo[3,2-f]quinazolines with small molecular size.
Ref 553123Isolation and expression of the Pneumocystis carinii dihydrofolate reductase gene. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8625-9.
Ref 534126J Med Chem. 1996 Feb 16;39(4):892-903.High-affinity inhibitors of dihydrofolate reductase: antimicrobial and anticancer activities of 7,8-dialkyl-1,3-diaminopyrrolo[3,2-f]quinazolines with small molecular size.

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