Drug Information

General Information of This Drug
Drug ID DRG00406
Drug Name Monastrol
Synonyms
monastrol; 329689-23-8; 254753-54-3; DL-Monastrol; ETHYL 4-(3-HYDROXYPHENYL)-6-METHYL-2-THIOXO-1,2,3,4-TETRAHYDROPYRIMIDINE-5-CARBOXYLATE; 4-(3-Hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-4H-pyrimidin-5-carboxylic Acid Ethyl Ester; ethyl 4-(3-hydroxyphenyl)-6-methyl-2-sulfanylidene-3,4-dihydro-1H-pyrimidine-5-carboxylate; CHEBI:75382; ethyl 4-(3-hydroxyphenyl)-6-methyl-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carboxylate; (+/-)-Monastrol; 5-Pyrimidinecarboxylic acid,1,2,3,4-tetrahydro-4-(3-hydroxyphenyl)-6-methyl-2-thioxo-, ethyl ester; SR-01000357662; Monastrol?; ()-Monastrol; MFCD00813077; ( inverted exclamation markA)-Monastrol; (A+/-)-Monastrol; Probes1_000001; Probes1_000042; Probes1_000312; Probes2_000257; Probes2_000376; Lopac0_000821; Oprea1_487786; BSPBio_001273; CBDivE_015834; KBioGR_000613; KBioSS_000613; MLS006011746; C18H23NO3S; F3284-6466; SCHEMBL3168349; BCBcMAP01_000162; KBio2_000613; KBio2_003181; KBio2_005749; KBio3_001085; KBio3_001086; DTXSID10388124; CHEBI:143544; LOBCDGHHHHGHFA-UHFFFAOYSA-N; BDBM175356; Bio1_000459; Bio1_000948; Bio1_001437; Bio2_000467; Bio2_000947; DTXSID501317756; GLXC-04725; HMS1362O15; HMS1792O15; HMS1990O15; HMS3267N03; HMS3403O15; HMS3412E20; HMS3676E20; BCP06757; BCP19385; EX-A1988; EX-A4169; GR-322; HB2551; MFCD06762956; NSC716782; NSC829695; s8439; STK386781; ZINC00297106; Monastrol, >=98% (HPLC), solid; AKOS000295413; AKOS002264887; AKOS016068396; AKOS016315550; CCG-267397; CS-6183; HY-101071A; NSC-716782; NSC-829695; IDI1_002222; SMP1_000197; UPCMLD0ENAT5762435:001; NCGC00025103-01; NCGC00025103-02; NCGC00025103-03; NCGC00025103-04; AC-33010; AS-74678; NCI60_040353; SMR004703468; DB-048305; D84039; M 8515; EN300-1266062; A902103; J-016007; Q6898425; SR-01000357662-1; SR-01000357662-2; BRD-A78377521-001-02-2; BRD-A78377521-001-03-0; BRD-A78377521-001-05-5; Z57061994; 5-[[4-[(1-Methylcyclohexyl)methoxy] phenyl]methyl]-2,4-thiazolidinedione; Ethyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-4H-pyrimidin-5-carboxylate; ethyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-3,4-dihydro-1H-pyrimidine-5-carboxylate; ethyl 6-(3-hydroxyphenyl)-2-mercapto-4-methyl-1,6-dihydropyrimidine-5-carboxylate; ethyl 6-methyl-4-(3-hydroxyphenyl)-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate; rac-ethyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate; 6-Methyl-4-(3-hydroxyphenyl)-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester; Ethyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (11)
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Target(s) Kinesin-like protein KIF11 (KIF11)  Target Info 
Structure
Formula
C14H16N2O3S
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 292.36
Lipid-water partition coefficient (xlogp) 1.6
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 4
Rotatable Bond Count (rotbonds) 4
PubChem CID
2987927
Canonical smiles
CCOC(=O)C1=C(NC(=S)NC1C2=CC(=CC=C2)O)C
InChI
InChI=1S/C14H16N2O3S/c1-3-19-13(18)11-8(2)15-14(20)16-12(11)9-5-4-6-10(17)7-9/h4-7,12,17H,3H2,1-2H3,(H2,15,16,20)
InChIKey
LOBCDGHHHHGHFA-UHFFFAOYSA-N
IUPAC Name
ethyl 4-(3-hydroxyphenyl)-6-methyl-2-sulfanylidene-3,4-dihydro-1H-pyrimidine-5-carboxylate
The activity data of This Drug
Standard Type Value Disease Model Cell line Cell line ID Ref.
Half Maximal Effective Concentration (EC50) 1.2 uM Colon carcinoma HCT 116 cell CVCL_0291 [1]
Half Maximal Growth Inhibition (GI50) 31.6 uM T acute lymphoblastic leukemia CCRF-CEM cell CVCL_0207 [2]
Half Maximal Growth Inhibition (GI50) 31.6 uM T acute lymphoblastic leukemia MOLT-4 cell CVCL_0013 [2]
Half Maximal Growth Inhibition (GI50) 31.6 uM Normal COLO205 cell CVCL_F402 [2]
Half Maximal Growth Inhibition (GI50) 31.6 uM Non-small cell lung carcinoma NCI-H522 cell CVCL_1567 [2]
Half Maximal Growth Inhibition (GI50) 31.6 uM Melanoma SK-MEL-2 cell CVCL_0069 [2]
Half Maximal Growth Inhibition (GI50) 31.6 uM Leukemia SR cell CVCL_1711 [2]
Half Maximal Growth Inhibition (GI50) 31.6 uM Glioblastoma SF-295 cell CVCL_1690 [2]
Half Maximal Growth Inhibition (GI50) 31.6 uM Colon adenocarcinoma KM12 cell CVCL_1331 [2]
Half Maximal Growth Inhibition (GI50) 31.6 uM Chronic myeloid leukemia K562 cell CVCL_0004 [2]
Half Maximal Growth Inhibition (GI50) 39.8 uM Renal cell carcinoma SN12C cell CVCL_1705 [2]
Half Maximal Growth Inhibition (GI50) 39.8 uM Minimally invasive lung adenocarcinoma NCI-H322M cell CVCL_1557 [2]
Half Maximal Growth Inhibition (GI50) 39.8 uM Glioblastoma SNB-75 cell CVCL_1706 [2]
Half Maximal Growth Inhibition (GI50) 39.8 uM Cutaneous melanoma SK-MEL-5 cell CVCL_0527 [2]
Half Maximal Growth Inhibition (GI50) 39.8 uM Colon adenocarcinoma HCC 2998 cell CVCL_1266 [2]
Half Maximal Growth Inhibition (GI50) 39.8 uM Colon adenocarcinoma SW620 cell CVCL_0547 [2]
Half Maximal Growth Inhibition (GI50) 39.8 uM Colon adenocarcinoma HCT 15 cell CVCL_0292 [2]
Half Maximal Growth Inhibition (GI50) 50.1 uM Pleural epithelioid mesothelioma NCI-H226 cell CVCL_1544 [2]
Half Maximal Growth Inhibition (GI50) 50.1 uM Ovarian serous adenocarcinoma OVCAR-3 cell CVCL_0465 [2]
Half Maximal Growth Inhibition (GI50) 50.1 uM Ovarian endometrioid adenocarcinoma IGROV-1 cell CVCL_1304 [2]
Half Maximal Growth Inhibition (GI50) 50.1 uM Gliosarcoma SF539 cell CVCL_1691 [2]
Half Maximal Growth Inhibition (GI50) 63.1 uM Ovarian serous cystadenocarcinoma SK-OV-3 cell CVCL_0532 [2]
Half Maximal Growth Inhibition (GI50) 63.1 uM Ovarian adenocarcinoma OVCAR-4 cell CVCL_1627 [2]
Half Maximal Growth Inhibition (GI50) 63.1 uM Non-small cell lung carcinoma EKVX cell CVCL_1195 [2]
Half Maximal Growth Inhibition (GI50) 63.1 uM Melanoma UACC-257 cell CVCL_1779 [2]
Half Maximal Growth Inhibition (GI50) 63.1 uM Melanoma Malme-3M cell CVCL_1438 [2]
Half Maximal Growth Inhibition (GI50) 63.1 uM Lung adenocarcinoma NCI-H23 cell CVCL_1547 [2]
Half Maximal Growth Inhibition (GI50) 79.4 uM Renal adenocarcinoma ACHN cell CVCL_1067 [2]
Half Maximal Growth Inhibition (GI50) 79.4 uM Ovarian serous adenocarcinoma OVCAR-5 cell CVCL_1628 [2]
Half Maximal Growth Inhibition (GI50) 79.4 uM Melanoma LOX IMVI cell CVCL_1381 [2]
Half Maximal Growth Inhibition (GI50) 79.4 uM Cutaneous melanoma SK-MEL-28 cell CVCL_0526 [2]
Half Maximal Growth Inhibition (GI50) 79.4 uM Colon cancer HT29 cell CVCL_A8EZ [2]
Half Maximal Growth Inhibition (GI50) 79.4 uM Astrocytoma SNB-19 cell CVCL_0535 [2]
Half Maximal Growth Inhibition (GI50) 100 uM Renal carcinoma UO-31 cell CVCL_1911 [2]
Half Maximal Inhibitory Concentration (IC50) 45 ug/mL Invasive breast carcinoma MCF-7 cell CVCL_0031 [3]
Half Maximal Inhibitory Concentration (IC50) >10 uM Lung adenocarcinoma A-549 cell CVCL_0023 [4]
Half Maximal Inhibitory Concentration (IC50) >10 uM Gastric adenocarcinoma AGS cell CVCL_0139 [4]
Half Maximal Inhibitory Concentration (IC50) >100 uM Lung adenocarcinoma A-549 cell CVCL_0023 [5]
Each Peptide-drug Conjugate Related to This Drug
Full Information of The Activity Data of The PDC(s) Related to This Drug
NT4-MON ether [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [6]
Indication Solid tumor
Efficacy Data Cell viability 0.00%
Administration Time 6 days
Administration Dosage 0.03 mM
MOA of PDC
We have been studying protease-resistant branched peptides as tumor targeting agents by using tetra-branched peptides (NT4) containing the human regulatory peptide neurotensin (NT) sequence. Neurotensin receptors are overexpressed in several human malignancies, such as colon, pancreatic, prostate and small-cell lung cancer. We have been using NT4 conjugated to different functional units for tumor imaging and therapy, and found that NT4 conjugated to methotrexate produced 60% reduction of tumor growth in xenografted mice. Results obtained with NT4 indicated that branched peptides are promising novel multifunctional targeting molecules, which might allow cancer detection and therapy by means of the same molecule, with no modification in target binding, but rather a simple exchange of functional units. Since cancer cells are very different from one another in terms of drug sensibility, not only in different tumors but in different patients and stages of the disease, this approach prefigures the synthesis of a number of constructs conjugated with differently acting chemotherapeutics. The type of linkage between effector unit (drug/imaging agent etc.) and peptide is obviously crucial for this type of approach. The choice must be driven by two issues: 1) The nature of the drug functional groups available for coupling with the peptide; and 2) the mechanism-of-action of the drug. When a prodrug acts without being released from the carrier unit, a strong linker is preferred. However, if a drug has to be released in order to interact with the intracellular target, the linker must be cleavable. In latter, the linker has to be chosen properly-not too labile or leakage will occur during drug distribution, but not too robust or the pharmacological action will be impaired.

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Description
This clearly indicated that the chemotherapeutic moiety was released into the cell medium and the drug was internalized into the cells, probably by membrane diffusion. This became evident when observing the behavior of the unrelated conjugated peptides.
In Vitro Model Prostate carcinoma PC-3 cell CVCL_0035
Experiment 2 Reporting the Activity Data of This PDC [6]
Indication Solid tumor
Efficacy Data Cell viability 5.00%
Administration Time 6 days
Administration Dosage 0.03 mM
MOA of PDC
We have been studying protease-resistant branched peptides as tumor targeting agents by using tetra-branched peptides (NT4) containing the human regulatory peptide neurotensin (NT) sequence. Neurotensin receptors are overexpressed in several human malignancies, such as colon, pancreatic, prostate and small-cell lung cancer. We have been using NT4 conjugated to different functional units for tumor imaging and therapy, and found that NT4 conjugated to methotrexate produced 60% reduction of tumor growth in xenografted mice. Results obtained with NT4 indicated that branched peptides are promising novel multifunctional targeting molecules, which might allow cancer detection and therapy by means of the same molecule, with no modification in target binding, but rather a simple exchange of functional units. Since cancer cells are very different from one another in terms of drug sensibility, not only in different tumors but in different patients and stages of the disease, this approach prefigures the synthesis of a number of constructs conjugated with differently acting chemotherapeutics. The type of linkage between effector unit (drug/imaging agent etc.) and peptide is obviously crucial for this type of approach. The choice must be driven by two issues: 1) The nature of the drug functional groups available for coupling with the peptide; and 2) the mechanism-of-action of the drug. When a prodrug acts without being released from the carrier unit, a strong linker is preferred. However, if a drug has to be released in order to interact with the intracellular target, the linker must be cleavable. In latter, the linker has to be chosen properly-not too labile or leakage will occur during drug distribution, but not too robust or the pharmacological action will be impaired.

   Click to Show/Hide
Description
This clearly indicated that the chemotherapeutic moiety was released into the cell medium and the drug was internalized into the cells, probably by membrane diffusion. This became evident when observing the behavior of the unrelated conjugated peptides.
In Vitro Model Colon adenocarcinoma HT-29 cell CVCL_0320
Experiment 3 Reporting the Activity Data of This PDC [6]
Indication Solid tumor
Efficacy Data Cell viability 50.00%
Administration Time 6 days
Administration Dosage 0.03 mM
MOA of PDC
We have been studying protease-resistant branched peptides as tumor targeting agents by using tetra-branched peptides (NT4) containing the human regulatory peptide neurotensin (NT) sequence. Neurotensin receptors are overexpressed in several human malignancies, such as colon, pancreatic, prostate and small-cell lung cancer. We have been using NT4 conjugated to different functional units for tumor imaging and therapy, and found that NT4 conjugated to methotrexate produced 60% reduction of tumor growth in xenografted mice. Results obtained with NT4 indicated that branched peptides are promising novel multifunctional targeting molecules, which might allow cancer detection and therapy by means of the same molecule, with no modification in target binding, but rather a simple exchange of functional units. Since cancer cells are very different from one another in terms of drug sensibility, not only in different tumors but in different patients and stages of the disease, this approach prefigures the synthesis of a number of constructs conjugated with differently acting chemotherapeutics. The type of linkage between effector unit (drug/imaging agent etc.) and peptide is obviously crucial for this type of approach. The choice must be driven by two issues: 1) The nature of the drug functional groups available for coupling with the peptide; and 2) the mechanism-of-action of the drug. When a prodrug acts without being released from the carrier unit, a strong linker is preferred. However, if a drug has to be released in order to interact with the intracellular target, the linker must be cleavable. In latter, the linker has to be chosen properly-not too labile or leakage will occur during drug distribution, but not too robust or the pharmacological action will be impaired.

   Click to Show/Hide
Description
This clearly indicated that the chemotherapeutic moiety was released into the cell medium and the drug was internalized into the cells, probably by membrane diffusion. This became evident when observing the behavior of the unrelated conjugated peptides.
In Vitro Model Pancreatic ductal adenocarcinoma PANC-1 cell CVCL_0480
References
Ref 1 Design and synthesis of 2-amino-pyrazolopyridines as Polo-like kinase 1 inhibitors. Bioorg Med Chem Lett. 2008 Oct 15;18(20):5648-52. doi: 10.1016/j.bmcl.2008.08.095. Epub 2008 Aug 29.
Ref 2 Synthesis and characterization of tritylthioethanamine derivatives with potent KSP inhibitory activity. Bioorg Med Chem. 2011 Sep 15;19(18):5446-53. doi: 10.1016/j.bmc.2011.07.054. Epub 2011 Jul 30.
Ref 3 Synthesis and biological evaluation of conformationally flexible as well as restricted dimers of monastrol and related dihydropyrimidones. Eur J Med Chem. 2011 Aug;46(8):3274-81. doi: 10.1016/j.ejmech.2011.04.048. Epub 2011 May 5.
Ref 4 De novo design, synthesis and biological evaluation of 1,4-dihydroquinolin-4-ones and 1,2,3,4-tetrahydroquinazolin-4-ones as potent kinesin spindle protein (KSP) inhibitors. Bioorg Med Chem. 2011 Sep 15;19(18):5612-27. doi: 10.1016/j.bmc.2011.07.029. Epub 2011 Jul 22.
Ref 5 Dihydropyrimidine-2-thiones as Eg5 inhibitors and L-type calcium channel blockers: potential antitumour dual agents. Medchemcomm. 2019 Jul 4;10(9):1589-1598. doi: 10.1039/c9md00108e. eCollection 2019 Sep 1.
Ref 6 Design and in vitro evaluation of branched peptide conjugates: turning nonspecific cytotoxic drugs into tumor-selective agents. ChemMedChem. 2010 Apr 6;5(4):567-74. doi: 10.1002/cmdc.200900527.