Drug Details

General Information of the Drug (ID: DR8472)
Name
2-methoxyestradiol
Synonyms
ESM; Panzem; PulmoLAR; Panzem NCD; M 6383; (17beta)-2-Methoxyestra-1,3,5(10)-triene-3,17-diol; (17beta)-2-methoxyestra-1(10),2,4-triene-3,17-diol; (8R,9S,13S,14S,17S)-2-methoxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol; 1,3,5(10)-ESTRATRIEN-2,3,17-BETA-TRIOL 2-METHYL ETHER; 1,3,5(10)-Estratriene-2,3,17-triol 2-methyl ether; 2,3,17beta-Trihydroxy-1,3,5(10)-estratriene 2-methyl ether; 2-Hydroxyestradiol 2-methyl ether; 2-Hydroxyestradol 2-methyl ether; 2-ME2, 2-Methoxyestradiol; 2-Methoxyestra-1,3,5(10)-triene-3,17beta-diol; 2-Methoxyestradiol-17beta; 3,17beta-Dihydroxy-2-methoxy-1,3,5(10)-estratriene
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Molecular Type
Small molecule
Disease Pulmonary hypertension [ICD-11: BB01] Phase 2 [1]
Structure
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2D MOL

3D MOL

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Formula
C19H26O3
PubChem CID
66414
Canonical SMILES
CC12CCC3C(C1CCC2O)CCC4=CC(=C(C=C34)OC)O
InChI
1S/C19H26O3/c1-19-8-7-12-13(15(19)5-6-18(19)21)4-3-11-9-16(20)17(22-2)10-14(11)12/h9-10,12-13,15,18,20-21H,3-8H2,1-2H3/t12-,13+,15-,18-,19-/m0/s1
InChIKey
CQOQDQWUFQDJMK-SSTWWWIQSA-N
CAS Number
CAS 362-07-2
ChEBI ID
CHEBI:28955
TTD Drug ID
D06NYA
DrugBank ID
DB02342
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Arsenic trioxide      Realgar and orpiment     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP7  Molecule Info 
Pathway MAP
                    In-vitro Model SV-HUC-1 CVCL_3798 Healthy Homo sapiens
NTUB1 CVCL_RW29 Bladder carcinoma Homo sapiens
T24 CVCL_0554 Bladder carcinoma Homo sapiens
                    Experimental
                    Result(s)		 2-Methoxyestradiol Induces Mitotic Arrest, Apoptosis, and Synergistic Cytotoxicity with Arsenic Trioxide in Human Urothelial Carcinoma Cells.
          Eugenol      Coreopsis tinctoria     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
                    In-vitro Model LNCaP CVCL_0395 Prostate carcinoma Homo sapiens
PC-3 CVCL_0035 Prostate carcinoma Homo sapiens
DU145 CVCL_0105 Prostate carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combining 2-ME(2) with eugenol (i) inhibited growth of prostate cancer cells and induced apoptosis at lower concentrations than either single agent alone.
          Ferulic acid      Ferula sinkiangensisK     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression HSPD1  Molecule Info 
Pathway MAP
                    In-vitro Model A-375 CVCL_0132 Amelanotic melanoma Homo sapiens
                    Experimental
                    Result(s)		 2-Methoxyestradiol and its combination with ferulic acid induces melanoma cell death via downregulation of Hsp60 and Hsp90.
          Quercetin      Averrhoa carambola     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
                    In-vitro Model PC-3 CVCL_0035 Prostate carcinoma Homo sapiens
LNCaP CVCL_0395 Prostate carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination of quercetin and 2-Methoxyestradiol enhances inhibition of human prostate cancer LNCaP and PC-3 cells xenograft tumor growth.
Target and Pathway
Target(s) Hypoxia-inducible factor 1 alpha (HIF-1A)  Molecule Info  [6]
KEGG Pathway HIF-1 signaling pathway Click to Show/Hide
2 mTOR signaling pathway
3 Thyroid hormone signaling pathway
4 Pathways in cancer
5 Proteoglycans in cancer
6 Renal cell carcinoma
7 Central carbon metabolism in cancer
8 Choline metabolism in cancer
NetPath Pathway IL5 Signaling Pathway Click to Show/Hide
2 Notch Signaling Pathway
Panther Pathway Angiogenesis Click to Show/Hide
2 Hypoxia response via HIF activation
3 VEGF signaling pathway
Pathway Interaction Database AP-1 transcription factor network Click to Show/Hide
2 Hypoxic and oxygen homeostasis regulation of HIF-1-alpha
3 VEGFR1 specific signals
4 HIF-1-alpha transcription factor network
5 Notch-mediated HES/HEY network
Reactome Regulation of gene expression by Hypoxia-inducible Factor Click to Show/Hide
2 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
3 BMAL1:CLOCK,NPAS2 activates circadian gene expression
4 NOTCH1 Intracellular Domain Regulates Transcription
5 Circadian Clock
WikiPathways SIDS Susceptibility Pathways Click to Show/Hide
2 Notch Signaling Pathway
3 Vitamin D Receptor Pathway
4 Regulation of Hypoxia-inducible Factor (HIF) by Oxygen
5 Signaling by NOTCH1
6 Oncostatin M Signaling Pathway
7 Adipogenesis
8 AGE/RAGE pathway
9 Circadian Clock
10 Angiogenesis
References
Reference 1 HIF-1-alpha and survivin involved in the anti-apoptotic effect of 2ME2 after global ischemia in rats. Neurol Res. 2011 Jul;33(6):583-92.
Reference 2 2-methoxyestradiol induces mitotic arrest, apoptosis, and synergistic cytotoxicity with arsenic trioxide in human urothelial carcinoma cells. PLoS One. 2013 Aug 13;8(8):e68703.
Reference 3 Combination of 2-methoxyestradiol (2-ME2) and eugenol for apoptosis induction synergistically in androgen independent prostate cancer cells. J Steroid Biochem Mol Biol. 2009 Jan;113(1-2):25-35.
Reference 4 2-Methoxyestradiol and Its Combination with a Natural Compound, Ferulic Acid, Induces Melanoma Cell Death via Downregulation of Hsp60 and Hsp90. J Oncol. 2019 Oct 2;2019:9293416.
Reference 5 Combination of Quercetin and 2-Methoxyestradiol Enhances Inhibition of Human Prostate Cancer LNCaP and PC-3 Cells Xenograft Tumor Growth. PLoS One. 2015 May 26;10(5):e0128277.
Reference 6 2-methoxyestradiol inhibits hypoxia-inducible factor 1alpha, tumor growth, and angiogenesis and augments paclitaxel efficacy in head and neck squam... Clin Cancer Res. 2004 Dec 15;10(24):8665-73.
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