Detailed information for compound 257650

Basic information

Technical information
  • TDR Targets ID: 257650
  • Name: 5-methyl-6-[(3,4,5-trimethoxyphenyl)sulfanylm ethyl]pyrido[2,3-d]pyrimidine-2,4-diamine
  • MW: 387.456 | Formula: C18H21N5O3S
  • H donors: 2 H acceptors: 3 LogP: 2.39 Rotable bonds: 6
    Rule of 5 violations (Lipinski): 1
  • SMILES: COc1cc(SCc2cnc3c(c2C)c(N)nc(n3)N)cc(c1OC)OC
  • InChi: 1S/C18H21N5O3S/c1-9-10(7-21-17-14(9)16(19)22-18(20)23-17)8-27-11-5-12(24-2)15(26-4)13(6-11)25-3/h5-7H,8H2,1-4H3,(H4,19,20,21,22,23)
  • InChiKey: QLMIARUXUJWQRR-UHFFFAOYSA-N  

Network

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Synonyms

  • 5-methyl-6-[[(3,4,5-trimethoxyphenyl)thio]methyl]pyrido[2,3-d]pyrimidine-2,4-diamine
  • [2-amino-5-methyl-6-[[(3,4,5-trimethoxyphenyl)thio]methyl]pyrido[2,3-d]pyrimidin-4-yl]amine
  • 5-methyl-6-[(3,4,5-trimethoxyphenyl)sulfanylmethyl]pyrido[3,2-e]pyrimidine-2,4-diamine
  • 5-methyl-6-[[(3,4,5-trimethoxyphenyl)thio]methyl]pyrido[3,2-e]pyrimidine-2,4-diamine
  • [2-amino-5-methyl-6-[[(3,4,5-trimethoxyphenyl)thio]methyl]pyrido[3,2-e]pyrimidin-4-yl]amine
  • 2,4-Diamino-5-methylpyrido[2,3-d]pyrimidine, 6-[[(3,4,5-trimethoxyphenyl)thio]-methyl]-, hydrate, (0.65)
  • AIDS-040326
  • AIDS040326

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Mycobacterium avium Dihydrofolate reductase Starlite/ChEMBL References
Homo sapiens dihydrofolate reductase Starlite/ChEMBL References

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Mycobacterium leprae DIHYDROFOLATE REDUCTASE DFRA (DHFR) (TETRAHYDROFOLATE DEHYDROGENASE) Get druggable targets OG5_128410 All targets in OG5_128410
Candida albicans hypothetical protein Get druggable targets OG5_128410 All targets in OG5_128410
Echinococcus multilocularis dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Loa Loa (eye worm) dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Schistosoma mansoni dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Candida albicans dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Echinococcus granulosus dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Candida albicans dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Brugia malayi dihydrofolate reductase family protein Get druggable targets OG5_128410 All targets in OG5_128410
Schistosoma japonicum ko:K00287 dihydrofolate reductase [EC1.5.1.3], putative Get druggable targets OG5_128410 All targets in OG5_128410
Mycobacterium tuberculosis Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase) Get druggable targets OG5_128410 All targets in OG5_128410
Chlamydia trachomatis dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Brugia malayi Dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Mycobacterium ulcerans dihydrofolate reductase DfrA Get druggable targets OG5_128410 All targets in OG5_128410

By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
Cryptosporidium hominis chain A, crystal structure of Dhfr Dihydrofolate reductase   181 aa 199 aa 27.1 %
Onchocerca volvulus Putative dihydrofolate reductase Dihydrofolate reductase   181 aa 174 aa 31.6 %
Cryptosporidium parvum dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   181 aa 199 aa 27.1 %
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase dihydrofolate reductase 187 aa 202 aa 29.7 %

Obtained from network model

Ranking Plot


Putative Targets List


Species Potential target Raw Global Species
Mycobacterium ulcerans dihydrofolate reductase DfrA 0.0415 1 0.5
Echinococcus multilocularis dihydrofolate reductase 0.0415 1 1
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase 0.0159 0.3013 0.5
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase 0.0159 0.3013 0.5
Echinococcus granulosus dihydrofolate reductase 0.0415 1 1
Mycobacterium tuberculosis Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase) 0.0415 1 0.5
Chlamydia trachomatis dihydrofolate reductase 0.0415 1 0.5
Brugia malayi Muscleblind-like protein 0.0144 0.262 0.262
Schistosoma mansoni dihydrofolate reductase 0.0415 1 0.5
Loa Loa (eye worm) hypothetical protein 0.0144 0.262 0.262
Trypanosoma brucei dihydrofolate reductase-thymidylate synthase 0.0159 0.3013 0.5
Plasmodium vivax bifunctional dihydrofolate reductase-thymidylate synthase, putative 0.0159 0.3013 0.5
Loa Loa (eye worm) hypothetical protein 0.0144 0.262 0.262
Leishmania major dihydrofolate reductase-thymidylate synthase 0.0159 0.3013 0.5
Brugia malayi Dihydrofolate reductase 0.0415 1 1
Mycobacterium leprae DIHYDROFOLATE REDUCTASE DFRA (DHFR) (TETRAHYDROFOLATE DEHYDROGENASE) 0.0415 1 0.5
Loa Loa (eye worm) dihydrofolate reductase 0.0415 1 1
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase 0.0159 0.3013 0.5

Activities

Activity type Activity value Assay description Source Reference
Activity scale (binding) < 10 nM Antimycobacterial activity scale was evaluated and found to be highly active against MAC Dihydrofolate reductase ChEMBL. 11754578
Activity scale (binding) < 10 nM Antimycobacterial activity scale was evaluated and found to be highly active against MAC Dihydrofolate reductase ChEMBL. 11754578
Activity scale (binding) > 1000 nM Antimycobacterial activity scale was evaluated and found to be inactive against human Dihydrofolate reductase ChEMBL. 11754578
Activity scale (binding) > 1000 nM Antimycobacterial activity scale was evaluated and found to be inactive against human Dihydrofolate reductase ChEMBL. 11754578
IC50 (binding) = 4.5 nM Antimycobacterial activity against Mycobacterium avium complex diihydrofolate reductase (MAC DHFR) ChEMBL. 11754578
IC50 (binding) = 4.5 nM Antimycobacterial activity against Mycobacterium avium complex diihydrofolate reductase (MAC DHFR) ChEMBL. 11754578
IC50 (binding) = 1200 nM Antimycobacterial activity against human dihydrofolate reductase (hDHFR) ChEMBL. 11754578
IC50 (binding) = 1200 nM Antimycobacterial activity against human dihydrofolate reductase (hDHFR) ChEMBL. 11754578

Phenotypes

Whole-cell/tissue/organism interactions

We have no records of whole-cell/tissue assays done with this compound What does this mean?

Many chemical entities in TDR Targets come from high-throughput screenings with whole cells or tissue samples, and not all assayed compounds have been tested against a single a single target protein, probably because they get ruled out during screening process. Even if these compounds may have not been of interest in the original screening, they may come as interesting leads for other screening assays. Furthermore, we may be able to propose drug-target associations using chemical similarities and network patterns.

Annotated phenotypes:

We have no manually annotated phenotypes for this drug. What does this mean? / Care to help?
In TDR Targets, information about phenotypes that are caused by drugs, or by genetic manipulation of cells (e.g. gene knockouts or knockdowns) is manually curated from the literature. These descriptions help to describe the potential of the target for drug development. If no information is available for this gene or if the information is incomplete, this may mean that i) the papers containing this information either appeared after the curation effort for this organism was carried out or they were inadvertently missed by curators; or that ii) the curation effort for this organism has not yet started.
 
In any case, if you have information about papers containing relevant validation data for this target, please log in using your TDR Targets username and password and send them to us using the corresponding form in this page (only visible to registered users) or contact us.

External resources for this compound

Bibliographic References

1 literature reference was collected for this gene.

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