RALTITREXED

/static/temp/default.svg Search structure
Synonyms
Status
Molecule Category Free-form
ATC L01BA03
UNII FCB9EGG971
EPA CompTox DTXSID0046482

Structure

InChI Key IVTVGDXNLFLDRM-HNNXBMFYSA-N
Smiles Cc1nc(=O)c2cc(CN(C)c3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)s3)ccc2[nH]1
InChI
InChI=1S/C21H22N4O6S/c1-11-22-14-4-3-12(9-13(14)19(28)23-11)10-25(2)17-7-6-16(32-17)20(29)24-15(21(30)31)5-8-18(26)27/h3-4,6-7,9,15H,5,8,10H2,1-2H3,(H,24,29)(H,26,27)(H,30,31)(H,22,23,28)/t15-/m0/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C21H22N4O6S
Molecular Weight 458.5
AlogP 1.98
Hydrogen Bond Acceptor 7.0
Hydrogen Bond Donor 4.0
Number of Rotational Bond 9.0
Polar Surface Area 152.69
Molecular species ACID
Aromatic Rings 3.0
Heavy Atoms 32.0

Bioactivity

Mechanism of Action Action Reference
Thymidylate synthase inhibitor INHIBITOR PubMed PubMed
Protein: Thymidylate synthase
Description: Thymidylate synthase
Organism : Homo sapiens
P04818 ENSG00000176890
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Oxidoreductase
- 480-2300 - - -
Enzyme Transferase
- 260-8800 - 418 94
Membrane receptor
- 22-746 - - -
Transporter Electrochemical transporter SLC superfamily of solute carriers SLC19 family of vitamin transporters
- 6-6 - - -
Transporter Electrochemical transporter SLC superfamily of solute carriers SLC46 family of folate transporters
- 100-100 - - -
Assay Description Organism Bioactivity Reference
Growth inhibition of murine tumor L1210 cell line Mus musculus 9.0 nM
Inhibition of cell growth in culture against murine tumor L1210:1565 cell lines Mus musculus 760.0 nM
Compound was tested for the concentration to inhibit 50% of L1210:1565 cell growth. Mus musculus 960.0 nM
Tested for the concentration to inhibit 50% of L1210 cell growth in culture. Mus musculus 7.0 nM
The inhibitory concentration of compound was evaluated on Pneumocystis carini Thymidylate synthase Pneumocystis carinii 530.0 nM
The inhibitory concentration of compound was evaluated on Human thymidylate synthase None 880.0 nM
In vitro inhibition against L1210 thymidylate synthase (TS) None 670.0 nM
Inhibition of isolated thymidylate synthase partially purified from L1210 mouse leukemia cells None 670.0 nM
Compound was evaluated for inhibition of thymidylate synthase, partially purified from L1210 mouse leukemia cells that overproduce thymidylate synthase due to amplification of TS gene None 418.0 nM
Inhibitory concentration against isolated rat thymidylate synthase None 900.0 nM
Inhibitory concentration against human thymidylate synthase Homo sapiens 380.0 nM
Inhibition of recombinant human TS Homo sapiens 380.0 nM
Inhibition of human thymidylate synthase Homo sapiens 380.0 nM
Inhibition of human thymidylate synthase Homo sapiens 380.0 nM
Inhibition of Toxoplasma gondii thymidylate synthase Toxoplasma gondii 900.0 nM
Antiproliferative activity against human RFC expressing Chinese hamster PC43-10 cells Cricetulus griseus 6.3 nM
Antiproliferative activity against human FRalpha expressing Chinese hamster RT16 cells Cricetulus griseus 15.0 nM
Antiproliferative activity against human FRbeta expressing Chinese hamster D4 cells Cricetulus griseus 22.0 nM
Antiproliferative activity against human FRbeta expressing Chinese hamster D4 cells in presence of folic acid Cricetulus griseus 746.0 nM
Antiproliferative activity against human RFC and FRalpha expressing human KB cells Homo sapiens 5.9 nM
Antiproliferative activity against human RFC and FRalpha expressing human KB cells in presence of folic acid Homo sapiens 22.0 nM
Antiproliferative activity against human RFC and FRalpha expressing human IGROV1 cells Homo sapiens 12.6 nM
Antiproliferative activity against human RFC and FRalpha expressing human IGROV1 cells in presence of folic acid Homo sapiens 20.0 nM
Inhibition of colony formation in human KB cells at 1 uM Homo sapiens 99.0 %
Inhibition of human thymidylate synthase at 30 degC under pH 7.4 by spectrophotometry Homo sapiens 380.0 nM
Inhibition of Toxoplasma gondii TS at 30 degC under pH 7.4 by spectrophotometry Toxoplasma gondii 900.0 nM
Displacement of [3H]MTX from human RFC expressed in Chinese hamster PC43-10 cells at 10 uM Homo sapiens 50.0 %
Inhibition of human thymidylate synthase Homo sapiens 290.0 nM
Inhibition of Toxoplasma gondii thymidylate synthase Toxoplasma gondii 480.0 nM
Inhibition of thymidylate synthase None 676.08 nM
PUBCHEM_BIOASSAY: Luminescence Cell-Based Dose Confirmation HTS to Identify Compounds Cytotoxic to BJeLR RAS-Dependent Fibroblast. (Class of assay: confirmatory) [Related pubchem assays: 1674 (Project Summary), 1554 (Primary HTS)] Homo sapiens 192.0 nM
Antiproliferative activity against chinese hamster PC43-10 expressing human RFC assessed as reduction of viable cells after 96 hrs Cricetulus griseus 6.3 nM
Antiproliferative activity against chinese hamster RT16 cells expressing human FRalpha assessed as reduction of viable cells after 96 hrs Cricetulus griseus 15.0 nM
Antiproliferative activity against chinese hamster D4 cells expressing human FRbeta assessed as reduction of viable cells after 96 hrs Cricetulus griseus 22.0 nM
Antiproliferative activity against chinese hamster D4 cells expressing human FRbeta assessed as reduction of viable cells after 96 hrs in the presence of 200 nM folic acid Cricetulus griseus 746.0 nM
Antiproliferative activity against chinese hamster R2 cells expressing human PCFT assessed as reduction of viable cells after 96 hrs Cricetulus griseus 99.5 nM
Antiproliferative activity against human KB cells expressing human RFC, FRalpha and PCFT assessed as reduction of viable cells after 96 hrs Homo sapiens 5.9 nM
Antiproliferative activity against human KB cells expressing human RFC, FRalpha and PCFT assessed as reduction of viable cells after 96 hrs in the presence of 200 nM folic acid Homo sapiens 22.0 nM
Antiproliferative activity against human IGROV1 cells expressing human RFC, FRalpha and PCFT assessed as reduction of viable cells after 96 hrs Homo sapiens 12.6 nM
Antiproliferative activity against human IGROV1 cells expressing human RFC, FRalpha and PCFT assessed as reduction of viable cells after 96 hrs in the presence of 200 nM folic acid Homo sapiens 20.0 nM
Inhibition of human thymidylate synthase Homo sapiens 290.0 nM
Inhibition of Toxoplasma gondii thymidylate synthase Toxoplasma gondii 480.0 nM
Inhibition of human thymidylate synthase by spectrophotometric analysis Homo sapiens 380.0 nM
Inhibition of human recombinant His-tagged thymidylate synthase assessed as N5,N10-methylenetetrahydrofolate oxidation to dihydrofolate after 20 mins by UV spectrophotometric analysis Homo sapiens 260.0 nM
Inhibition of human recombinant His-tagged thymidylate synthase assessed as N5,N10-methylenetetrahydrofolate oxidation to dihydrofolate at 1 uM after 20 mins by UV spectrophotometric analysis relative to control Homo sapiens 94.23 %
Growth inhibition of human KB cells expressing human RFC/FRalpha/PCFT after 96 hrs by CellTiter-blue assay in presence of folic acid Homo sapiens 22.0 nM
Growth inhibition of human KB cells expressing human RFC/FRalpha/PCFT after 96 hrs by CellTiter-blue assay Homo sapiens 5.9 nM
Growth inhibition of Chinese hamster R2 cells expressing human PCFT4 after 96 hrs by CellTiter-blue assay Cricetulus griseus 99.5 nM
Growth inhibition of Chinese hamster D4 cells after 96 hrs by CellTiter-blue assay in presence of folic acid Cricetulus griseus 746.0 nM
Growth inhibition of Chinese hamster D4 cells after 96 hrs by CellTiter-blue assay Cricetulus griseus 22.0 nM
Growth inhibition of Chinese hamster RT16 cells after 96 hrs by CellTiter-blue assay Cricetulus griseus 15.0 nM
Growth inhibition of Chinese hamster PC43-10 cells after 96 hrs by CellTiter-blue assay Cricetulus griseus 6.3 nM
Cytotoxicity against chinese hamster R2 cells expressing human PCFT4 after 96 hrs by CellTitre-Blue fluorescence assay Cricetulus griseus 99.5 nM
Inhibition of RFC (unknown origin) expressed in Chinese hamster PC43-10 cells assessed as cell growth inhibition incubated up to 96 hrs by Celltiter-blue cell viability assay Homo sapiens 6.3 nM
Inhibition of FRalpha (unknown origin) expressed in Chinese hamster RT16 cells assessed as cell growth inhibition incubated up to 96 hrs by Celltiter-blue cell viability assay Homo sapiens 15.0 nM
Inhibition of FRbeta (unknown origin) expressed in Chinese hamster D4 cells assessed as cell growth inhibition incubated up to 96 hrs by Celltiter-blue cell viability assay Homo sapiens 22.0 nM
Inhibition of FRbeta (unknown origin) expressed in Chinese hamster D4 cells assessed as cell growth inhibition incubated up to 96 hrs in presence of 200 nM folic acid by Celltiter-blue cell viability assay Homo sapiens 746.0 nM
Inhibition of PCFT (unknown origin) expressed in Chinese hamster R2/PCFT4 cells assessed as cell growth inhibition incubated up to 96 hrs by Celltiter-blue cell viability assay Homo sapiens 99.5 nM
Cytotoxicity against human KB cells assessed as cell growth inhibition incubated up to 96 hrs by Celltiter-blue cell viability assay Homo sapiens 5.9 nM
Cytotoxicity against human KB cells assessed as cell growth inhibition incubated up to 96 hrs in presence of 200 nM folic acid by Celltiter-blue cell viability assay Homo sapiens 22.0 nM
Inhibition of human thymidylate synthase using dUMP/(6R,S)-tetrahydrofolate as substrate/co-factor by spectrophotometric method Homo sapiens 380.0 nM
Binding affinity to human FR-beta receptor expressed in Chinese hamster D4 cells assessed as antiproliferative activity measured as reduction in cell viability after 96 hrs in presence of folic acid by Cell-Titer Blue assay Homo sapiens 746.0 nM
Binding affinity to human RFC expressed in Chinese hamster PC43-10 cells assessed as antiproliferative activity measured as reduction in cell viability after 96 hrs by Cell-Titer Blue assay Homo sapiens 6.3 nM
Cytotoxicity in RFC-null Chinese hamster R2 cells assessed as reduction in cell viability measured after 96 hrs by Cell-Titer Blue assay Cricetulus griseus 15.0 nM
Binding affinity to human FR-alpha receptor expressed in Chinese hamster RT16 cells assessed as antiproliferative activity measured as reduction in cell viability after 96 hrs by Cell-Titer Blue assay Homo sapiens 15.0 nM
Binding affinity to human FR-beta receptor expressed in Chinese hamster D4 cells assessed as antiproliferative activity measured as reduction in cell viability after 96 hrs by Cell-Titer Blue assay Homo sapiens 22.0 nM
Binding affinity to human PCFT expressed in Chinese hamster R2/PCFT4 cells assessed as antiproliferative activity measured as reduction in cell viability after 96 hrs by Cell-Titer Blue assay Homo sapiens 99.5 nM
Antiproliferative activity against human KB cells expressing human RFC/FR-alpha/PCFT assessed as reduction in cell viability measured after 96 hrs by Cell-Titer Blue assay Homo sapiens 5.9 nM
Antiproliferative activity against human KB cells expressing human RFC/FR-alpha/PCFT assessed as reduction in cell viability measured after 96 hrs in presence of folic acid by Cell-Titer Blue assay Homo sapiens 22.0 nM
Antibacterial activity against Staphylococcus aureus MRSA ATCC 43300 (CO-ADD:GP_020); MIC in CAMBH media, using NBS plates, by OD(600) Staphylococcus aureus subsp. aureus 9.09 %
Antibacterial activity against Escherichia coli ATCC 25922 (CO-ADD:GN_001); MIC in CAMBH media using NBS plates, by OD(600) Escherichia coli 2.78 %
Antibacterial activity against Klebsiella pneumoniae MDR ATCC 70063 (CO-ADD:GN_003); MIC in CAMBH media using NBS plates, by OD(600) Klebsiella pneumoniae 9.17 %
Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 (CO-ADD:GN_042); MIC in CAMBH media using NBS plates, by OD(600) Pseudomonas aeruginosa 12.62 %
Antibacterial activity against Acinetobacter baumannii ATCC 19606 (CO-ADD:GN_034); MIC in CAMBH media using NBS plates, by OD600 Acinetobacter baumannii 12.09 %
Antifungal activity against Candida albicans ATCC 90028 (CO-ADD:FG_001); MIC in YNB media using NBS plates, by OD630 Candida albicans 2.26 %
Antifungal activity against Cryptococcus neoformans H99 ATCC 208821 (CO-ADD:FG_002); MIC in YNB media using NBS plates, by Resazurin OD(600-570) Cryptococcus neoformans -0.58 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Homo sapiens -6.67 %
Cytotoxicity in RFC-null Chinese hamster R2 cells assessed as reduction in cell viability measured after 96 hrs by Cell-Titer Blue fluorescence analysis Cricetulus griseus 15.0 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 24.87 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 17.58 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 -1.269 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.03 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.13 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.26 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.13 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.26 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.03 %

Cross References

Resources Reference
ChEBI 5847
ChEMBL CHEMBL225071
DrugBank DB00293
DrugCentral 2353
FDA SRS FCB9EGG971
Human Metabolome Database HMDB0014438
Guide to Pharmacology 7403
KEGG C11372
PDB D16
PharmGKB PA131625240
PubChem 135400182
SureChEMBL SCHEMBL7438
ZINC ZINC000003832372
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