Details
Stereochemistry | EPIMERIC |
Molecular Formula | C32H47F5O3S |
Molecular Weight | 606.771 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 6 / 7 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]3([H])C4=C(C[C@@H](CCCCCCCCC[S+]([O-])CCCC(F)(F)C(F)(F)F)[C@@]23[H])C=C(O)C=C4
InChI
InChIKey=VWUXBMIQPBEWFH-WCCTWKNTSA-N
InChI=1S/C32H47F5O3S/c1-30-17-15-26-25-12-11-24(38)21-23(25)20-22(29(26)27(30)13-14-28(30)39)10-7-5-3-2-4-6-8-18-41(40)19-9-16-31(33,34)32(35,36)37/h11-12,21-22,26-29,38-39H,2-10,13-20H2,1H3/t22-,26-,27+,28+,29-,30+,41?/m1/s1
Molecular Formula | C32H47F5O3S |
Molecular Weight | 606.771 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 5 / 6 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: http://www.drugbank.ca/drugs/DB00947Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/ppa/fulvestrant.html
Sources: http://www.drugbank.ca/drugs/DB00947
Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/ppa/fulvestrant.html
Fulvestrant is a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor. Fulvestrant competitively and reversibly binds to estrogen receptors present in cancer cells and achieves its anti-estrogen effects through two separate mechanisms. First, fulvestrant binds to the receptors and downregulates them so that estrogen is no longer able to bind to these receptors. Second, fulvestrant degrades the estrogen receptors to which it is bound. Both of these mechanisms inhibit the growth of tamoxifen-resistant as well as estrogen-sensitive human breast cancer cell lines. Fulvestrant is used for the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy. Fulvestrant is marketed under the trade name Faslodex, by AstraZeneca.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16251200
Curator's Comment: Fulvestrant does not cross the blood–brain barrier
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26407012 |
0.0631 nM [IC50] | ||
Target ID: CHEMBL387 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26407012 |
0.1 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | FASLODEX Approved UseFASLODEX is an estrogen receptor antagonist indicated for the:
Treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following
antiestrogen therapy. Launch Date1.01753278E12 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
25.1 ng/mL |
500 mg single, intramuscular dose: 500 mg route of administration: Intramuscular experiment type: SINGLE co-administered: |
FULVESTRANT plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
11400 ng × h/mL |
500 mg single, intramuscular dose: 500 mg route of administration: Intramuscular experiment type: SINGLE co-administered: |
FULVESTRANT plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
40 day |
250 mg single, intramuscular dose: 250 mg route of administration: Intramuscular experiment type: SINGLE co-administered: |
FULVESTRANT plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
500 mg 1 times / month multiple, intramuscular Highest studied dose Dose: 500 mg, 1 times / month Route: intramuscular Route: multiple Dose: 500 mg, 1 times / month Sources: |
unhealthy, 54 years n = 1 Health Status: unhealthy Condition: breast cancer Age Group: 54 years Sex: F Population Size: 1 Sources: |
|
500 mg 1 times / month multiple, intramuscular Dose: 500 mg, 1 times / month Route: intramuscular Route: multiple Dose: 500 mg, 1 times / month Sources: |
unhealthy, 56 years n = 1 Health Status: unhealthy Condition: ductal carcinoma of the breast Age Group: 56 years Sex: F Population Size: 1 Sources: |
Disc. AE: Epidermal necrolysis... AEs leading to discontinuation/dose reduction: Epidermal necrolysis (1 patient) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Epidermal necrolysis | 1 patient Disc. AE |
500 mg 1 times / month multiple, intramuscular Dose: 500 mg, 1 times / month Route: intramuscular Route: multiple Dose: 500 mg, 1 times / month Sources: |
unhealthy, 56 years n = 1 Health Status: unhealthy Condition: ductal carcinoma of the breast Age Group: 56 years Sex: F Population Size: 1 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | no (co-administration study) Comment: label: administration with rifampin (inducer) showed not effect on PK of fulvestrant Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Estrogenicity of bisphenol A in a human endometrial carcinoma cell line. | 1999 Apr 25 |
|
Methoxychlor stimulates estrogen-responsive messenger ribonucleic acids in mouse uterus through a non-estrogen receptor (non-ER) alpha and non-ER beta mechanism. | 1999 Aug |
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The aryl hydrocarbon receptor (AHR)/AHR nuclear translocator (ARNT) heterodimer interacts with naturally occurring estrogen response elements. | 1999 Nov 25 |
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Modulation of aromatase expression in human breast tissue. | 2001 Dec |
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Transcriptional activation of heat shock protein 27 gene expression by 17beta-estradiol and modulation by antiestrogens and aryl hydrocarbon receptor agonists. | 2001 Feb |
|
Effects of beta-estradiol and bisphenol A on heat shock protein levels and localization in the mouse uterus are antagonized by the antiestrogen ICI 182,780. | 2001 Oct |
|
Infertility and testicular atrophy in the antiestrogen-treated adult male rat. | 2001 Sep |
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Comparison of an array of in vitro assays for the assessment of the estrogenic potential of natural and synthetic estrogens, phytoestrogens and xenoestrogens. | 2001 Sep 14 |
|
Stimulation of alkaline phosphatase activity in Ishikawa cells induced by various phytoestrogens and synthetic estrogens. | 2002 Dec |
|
Estradiol enhances and estriol inhibits the expression of CYP1A1 induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in a mouse ovarian cancer cell line. | 2002 Jul 15 |
|
Triphenylethylene antiestrogen-induced acute relaxation of mouse duodenal muscle. Possible involvement of Ca2+ channels. | 2002 Jun 12 |
|
Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland. | 2003 Aug |
|
BMP7/ActRIIB regulates estrogen-dependent apoptosis: new biomarkers for environmental estrogens. | 2004 |
|
Effects of the pesticides prochloraz and methiocarb on human estrogen receptor alpha and beta mRNA levels analyzed by on-line RT-PCR. | 2004 Aug |
|
Effect of anti-estrogens on the androgen receptor activity and cell proliferation in prostate cancer cells. | 2004 Dec |
|
Augmented endothelial nitric oxide synthase (eNOS) protein expression in human pregnant myometrium: possible involvement of eNOS promoter activation by estrogen via both estrogen receptor (ER)alpha and ERbeta. | 2004 Feb |
|
Identification of estrogen-responsive genes by complementary deoxyribonucleic acid microarray and characterization of a novel early estrogen-induced gene: EEIG1. | 2004 Feb |
|
Estrogen receptor alpha, but not beta, plays a major role in 17beta-estradiol-induced murine cholesterol gallstones. | 2004 Jul |
|
Fulvestrant is an effective and well-tolerated endocrine therapy for postmenopausal women with advanced breast cancer: results from clinical trials. | 2004 Mar |
|
Resveratrol modulates the phosphoinositide 3-kinase pathway through an estrogen receptor alpha-dependent mechanism: relevance in cell proliferation. | 2004 Mar 20 |
|
Small nuclear RING finger protein expression during gonad development: regulation by gonadotropins and estrogen in the postnatal ovary. | 2004 May |
|
Short-chain fatty acids enhance nuclear receptor activity through mitogen-activated protein kinase activation and histone deacetylase inhibition. | 2004 May 4 |
|
Estrogen modulates microglial inflammatory mediator production via interactions with estrogen receptor beta. | 2004 Nov |
|
Leptin interferes with the effects of the antiestrogen ICI 182,780 in MCF-7 breast cancer cells. | 2004 Oct 1 |
|
Differential responses to doxorubicin-induced phosphorylation and activation of Akt in human breast cancer cells. | 2005 |
|
Endocrinology and hormone therapy in breast cancer: selective oestrogen receptor modulators and downregulators for breast cancer - have they lost their way? | 2005 |
|
Transcriptional activation of the oxytocin promoter by oestrogens uses a novel non-classical mechanism of oestrogen receptor action. | 2005 Apr |
|
Selective oestrogen receptor modulators, aromatase inhibitors and the female breast. | 2005 Aug |
|
Alternative splicing of Slo channel gene programmed by estrogen, progesterone and pregnancy. | 2005 Aug 29 |
|
Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR). | 2005 Dec 1 |
|
ERE-independent ERalpha target genes differentially expressed in human breast tumors. | 2005 Dec 21 |
|
Novel progestogenic activity of environmental endocrine disruptors in the upregulation of calbindin-D9k in an immature mouse model. | 2005 Jan |
|
Opposite effects of estrogen receptors alpha and beta on MCF-7 sensitivity to the cytotoxic action of TNF and p53 activity. | 2005 Jul 14 |
|
Differential effects of estrogen receptor antagonists on pituitary lactotroph proliferation and prolactin release. | 2005 Jul 15 |
|
Receptor isoform and ligand-specific modulation of dihydrotestosterone-induced prostate specific antigen gene expression and prostate tumor cell growth by estrogens. | 2005 Jul-Aug |
|
Regulation of vitamin D receptor expression via estrogen-induced activation of the ERK 1/2 signaling pathway in colon and breast cancer cells. | 2005 Jun |
|
The estrogenic activity of synthetic progestins used in oral contraceptives enhances fatty acid synthase-dependent breast cancer cell proliferation and survival. | 2005 Jun |
|
[Regulation of orphan receptor ERR alpha by estrogen and progesterone in endometrial carcinoma cell line]. | 2005 Jun 18 |
|
Estrogen-induced loss of progesterone receptor expression in normal and malignant ovarian surface epithelial cells. | 2005 Jun 23 |
|
Differential effects of estrogens and progestins on the anticoagulant tissue factor pathway inhibitor in the rat. | 2005 Mar |
|
Promoting insulin secretion in pancreatic islets by means of bisphenol A and nonylphenol via intracellular estrogen receptors. | 2005 May |
|
Estrogenic effects of two derivatives of icariin on human breast cancer MCF-7 cells. | 2005 Nov |
|
Estrogen receptor alpha increases basal and cigarette smoke extract-induced expression of CYP1A1 and CYP1B1, but not GSTP1, in normal human bronchial epithelial cells. | 2005 Nov |
|
The phytoestrogen biochaninA weakens acute cardiac allograft rejection without affecting the reproductive system. | 2005 Oct |
|
Estrogen increases mitochondrial efficiency and reduces oxidative stress in cerebral blood vessels. | 2005 Oct |
|
Effect of methoxychlor and estradiol on cytochrome p450 enzymes in the mouse ovarian surface epithelium. | 2006 Feb |
|
Dioxin induces an estrogen-like, estrogen receptor-dependent gene expression response in the murine uterus. | 2006 May |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/fulvestrant.html
Usual Adult Dose for Breast Cancer
Initial dose: 500 mg IM on days 1, 15, and 29, then once a month thereafter.
Route of Administration:
Intramuscular
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24793639
In human and rat mesangial cells, increased type IV collagen and fibronectin gene transcription induced by TGF-b1 was downregulated by Fulvestrant at concentrations ranging from 10(-10) M to 10(-7) M.
Substance Class |
Chemical
Created
by
admin
on
Edited
Wed Jul 05 23:20:03 UTC 2023
by
admin
on
Wed Jul 05 23:20:03 UTC 2023
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Record UNII |
22X328QOC4
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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WHO-VATC |
QL02BA03
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LIVERTOX |
NBK548072
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NDF-RT |
N0000175582
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NCI_THESAURUS |
C2116
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NDF-RT |
N0000000168
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WHO-ATC |
L02BA03
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NDF-RT |
N0000175826
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EMA ASSESSMENT REPORTS |
FASLODEX (AUTHORIZED: BREAST NEOPLASMS)
Created by
admin on Wed Jul 05 23:20:03 UTC 2023 , Edited by admin on Wed Jul 05 23:20:03 UTC 2023
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Code System | Code | Type | Description | ||
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7658
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N0000000145
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PRIMARY | Estrogen Receptor Antagonists [MoA] | ||
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1255
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PRIMARY | |||
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DB00947
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22X328QOC4
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282357
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PRIMARY | RxNorm | ||
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759879
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PRIMARY | |||
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C1379
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22X328QOC4
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100000089504
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7712
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KK-128
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31638
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129453-61-8
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SUB13933MIG
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FULVESTRANT
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104741
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1286650
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1015
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M5583
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PRIMARY | Merck Index | ||
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CHEMBL1358
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DTXSID4022369
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C070081
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Related Record | Type | Details | ||
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (HPLC)
USP
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (HPLC)
EP
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TARGET -> INHIBITOR |
IC50
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TARGET -> INHIBITOR |
Selective estrogen receptor degrader (SERD)
BINDING
IC50
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BINDER->LIGAND |
BINDING
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TARGET -> INHIBITOR |
Binding assay
IC50
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METABOLIC ENZYME -> SUBSTRATE |
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CELL->INHIBITOR |
Viablity
IC50
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TARGET->DEGRADER, SELECTIVE |
100% Degradation as control
EC50
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TARGET->DEGRADER, SELECTIVE |
Selective estrogen receptor degrader (SERD)
BINDING
IC50
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Related Record | Type | Details | ||
---|---|---|---|---|
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
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METABOLITE LESS ACTIVE -> PARENT |
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METABOLITE -> PARENT |
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PARENT -> METABOLITE ACTIVE |
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Related Record | Type | Details | ||
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
For the calculation of contents, multiply the peak areas by 0.3
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
For the calculation of contents, multiply the peak areas by 0.7
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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