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(2R,6S,7R)-7-(4-hydroxyphenyl)-8-oxatricyclo[7.4.0.0^{2,6}]trideca-1(13),9,11-trien-12-ol
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ChemBase ID:
5563
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Molecular Formular:
C18H18O3
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Molecular Mass:
282.33372
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Monoisotopic Mass:
282.12559444
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SMILES and InChIs
SMILES:
[C@H]12c3cc(ccc3O[C@H]([C@H]1CCC2)c1ccc(cc1)O)O
Canonical SMILES:
Oc1ccc(cc1)[C@@H]1Oc2ccc(cc2[C@H]2[C@@H]1CCC2)O
InChI:
InChI=1S/C18H18O3/c19-12-6-4-11(5-7-12)18-15-3-1-2-14(15)16-10-13(20)8-9-17(16)21-18/h4-10,14-15,18-20H,1-3H2/t14-,15+,18+/m1/s1
InChIKey:
XIESSJVMWNJCGZ-VKJFTORMSA-N
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Cite this record
CBID:5563 http://www.chembase.cn/molecule-5563.html
NAMES AND DATABASE IDS
NAMES AND DATABASE IDS
Names Database IDs
IUPAC name
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(2R,6S,7R)-7-(4-hydroxyphenyl)-8-oxatricyclo[7.4.0.0^{2,6}]trideca-1(13),9,11-trien-12-ol
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(2R,6S,7R)-7-(4-hydroxyphenyl)-8-oxatricyclo[7.4.0.0^{2,6}]trideca-1(9),10,12-trien-12-ol
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IUPAC Traditional name
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(2R,6S,7R)-7-(4-hydroxyphenyl)-8-oxatricyclo[7.4.0.0^{2,6}]trideca-1(13),9,11-trien-12-ol
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(2R,6S,7R)-7-(4-hydroxyphenyl)-8-oxatricyclo[7.4.0.0^{2,6}]trideca-1(9),10,12-trien-12-ol
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Synonyms
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(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-1,2,3,3A,4,9B-HEXAHYDROCYCLOPENTA[C]CHROMEN-8-OL
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LY500307
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CAS Number
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PubChem SID
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PubChem CID
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DATA SOURCES
DATA SOURCES
All Sources Commercial Sources Non-commercial Sources
CALCULATED PROPERTIES
CALCULATED PROPERTIES
JChem
ALOGPS 2.1
Acid pKa
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9.352871
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H Acceptors
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3
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H Donor
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2
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LogD (pH = 5.5)
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4.1099153
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LogD (pH = 7.4)
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4.10518
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Log P
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4.109976
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Molar Refractivity
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80.4954 cm3
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Polarizability
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31.31295 Å3
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Polar Surface Area
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49.69 Å2
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Rotatable Bonds
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1
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Lipinski's Rule of Five
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true
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Log P
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3.85
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LOG S
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-4.24
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Solubility (Water)
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1.62e-02 g/l
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DETAILS
DETAILS
DrugBank
Selleck Chemicals
Selleck Chemicals -
S1598
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Research Area
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Description
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Endocrinology |
Biological Activity
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Description
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LY500307 (SERBA-1) is a potent, selective estrogen receptor β agonist with EC50 of 0.66 nM. |
Targets
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Estrogen receptor β |
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IC50 |
0.66 nM (EC50) [1] |
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In Vitro
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LY500307 shows potent binding affinity for both ERα (Ki 2.68 nM) and ERβ (Ki 0.19 nM), which exhibits 14-fold binding selectivity for the β isoform, generated using 3H-estradiol and recombinant, full-length, human ERs in a competitive binding assay. LY500307 shows full agonist function in both ERα and ERβ assays (>90% relative efficacy), displays potent inhibition toward ERβ with EC50 of 0.66 nM exhibiting 32 fold specificity for ERβ than for ERα which has EC50 of 19.4 nM measured using a transcription assay in the cotransfected human prostate cancer PC3/ER (α or β)-ERE cell line. LY500307/ERα and LY500307/ERβ X-ray cocrystal structures show significant differences in the manner in which LY500307 binds within the binding pockets. LY500307 displays a different orientation corresponding to a (ca. 180°) rotation on its bisphenol axis, and the A ring phenol of LY500307, while bound to histidine in both structures, locates to different sides of the imidazole functionality for this interaction explaining the observed selectivity of LY500307 for ERβ. [1] |
In Vivo
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Oral administration of LY500307 (0.01-0.05 mg/kg) in CD-1 mice produces the reduction on prostate weights in a dose-response manner, has no effect on testes and SV weights in this dose range and no effect on T and DHT levels at up to 10× the minimum efficacy dose (0.1 mg/kg), while the nonselective ER agonist diethylstilbestrol (DES) shows significant regression of prostate, testes, and SV and also lowering T and DHT. [1] |
Clinical Trials
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The phase II study to evaluate daily oral doses of LY500307 for 24 weeks in men with lower urinary tract symptoms (LUTS) and prostatic enlargement secondary to benign prostatic hyperplasia (BPH) has been terminated due to insufficient efficacy. |
Features
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LY500307 shows significantly higher binding activity toward ERβ than ERα. |
Protocol
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Kinase Assay
[1]
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Cell-Based Transcriptional Assays |
PC3 human prostatic adenocarcinoma cells are transiently cotransfected with plasmid carrying either full length human ERα or full length human ERβ and a reporter plasmid using fugene 6 transfection reagent. Human ERα or human ERβ are constitutively expressed using plasmids containing the cytomegalovirus (CMV) promoter. Reporter plasmids for the ER CTF assays contain 3X human ERE plus the thymidine kinase (TK) promoter upstream of the luciferase reporter cDNA. Efficacy is determined relative to the reference molecule diethylstilbestrol. EC50 values are determined by computer fit to a concentration-response curve. |
Animal Study
[1]
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Animal Models |
CD-1 mice |
Formulation |
Dissolved in the solution containing 1% carbxymethyl cellulose and 0.25% Tween 80. |
Doses |
0.01-0.05 mg/kg |
Administration |
Oral gavage daily |
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PATENTS
PATENTS
PubChem Patent
Google Patent