Drug Details

General Information of the Drug (ID: DR4213)
Name
Raloxifene
Synonyms
raloxifene; 84449-90-1; Keoxifene; Evista; Raloxifenum [Latin]; Raloxifeno [Spanish]; Raloxifenum; Raloxifeno; LY 139481; LY-139481; UNII-YX9162EO3I; Optruma; CHEMBL81; Keoxifene; LY 139481;; CHEBI:8772; YX9162EO3I; RAL; LY139481; CCRIS 7129; HSDB 7460; NCGC00015889-05; CAS-82640-04-8; Pharoxifene; Raloxifene D4; Raloxifene, 6; Raloxifene (INN); Eviden (TN); Raxeto (TN); Lopac-R-1402; DSSTox_CID_3550; SCHEMBL6144; DSSTox_RID_77076; DSSTox_GSID_23550; Lopac0_001051; BSPBio_000903; KBioGR_002361; KBioSS_002364; BIDD:ER0216; BIDD:GT0795; SPBio_002824; BPBio1_000995; GTPL2820; DTXSID3023550; BDBM19441; KBio2_002361; KBio2_004929; KBio2_007497; KBio3_002840; cid_11071264; cMAP_000032; HMS2089F06; HMS3742O11; ZINC538275; BCP09772; Tox21_202603; MFCD00866415; NSC747974; NSC761389; s5781; AKOS015896267; AC-8399; CCG-205128; DB00481; MCULE-4598311006; NSC-747974; NSC-761389; SDCCGSBI-0051021.P003; MRF-0000684; SMP2_000095; AS-35086; HY-13738; J22.982B; SBI-0051021.P002; AB0073011; CAS-84449-90-1; CS-0007764; FT-0674305; VU0155042-3; C07228; D08465; 449R901; Q425223; BRD-K63828191-003-11-5;
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Molecular Type
Small molecule
Disease Osteoporosis [ICD-11: FB83] Approved [1]
Structure
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2D MOL

3D MOL

ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 24.2 mcgh/L
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 1.36 mcg/L
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 32.5 h
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability
Clearance
The apparent oral clearance of drug is 44.1 L/h/kg
Elimination
0.002% of drug is excreted from urine in the unchanged form, and 6% drug is excreted as glucuronide conjugates
Half-life
The concentration or amount of drug in body reduced by one-half in 27 - 32 hours
Metabolism
The drug is metabolized via the liver
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 21.11506 micromolar/kg/day
Unbound Fraction
The unbound fraction of drug in plasma is 0.05%
Vd
The volume of distribution (Vd) of drug is 2348 L/kg
Water Solubility
The ability of drug to dissolve in water is measured as 0.013 mg/mL
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C28H27NO4S
PubChem CID
5035
Canonical SMILES
C1CCN(CC1)CCOC2=CC=C(C=C2)C(=O)C3=C(SC4=C3C=CC(=C4)O)C5=CC=C(C=C5)O
InChI
1S/C28H27NO4S/c30-21-8-4-20(5-9-21)28-26(24-13-10-22(31)18-25(24)34-28)27(32)19-6-11-23(12-7-19)33-17-16-29-14-2-1-3-15-29/h4-13,18,30-31H,1-3,14-17H2
InChIKey
GZUITABIAKMVPG-UHFFFAOYSA-N
CAS Number
CAS 84449-90-1
TTD Drug ID
D01XBA
DrugBank ID
DB00481
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Epigallocatechin gallate      Hamamelis virginiana     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     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		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation JNK2  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation mTOR  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation S6K1  Molecule Info 
Pathway MAP
                    In-vitro Model MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 The combination of EGCG and raloxifene effectively reduced the mitogenic and survival signaling in MDA-MB-231 cells.
          Resveratrol      Gnetum parvifolium     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
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination of Res and Ral via increased expression of apoptotic genes including Bax, p53 and caspase-3 and caspase-8 is able to promote apoptosis as a mitochondrial dependent pathway in MCF7 and MDA-MB-231.
Target and Pathway
Target(s) Estrogen receptor (ESR)  Molecule Info  [4]
KEGG Pathway Estrogen signaling pathway Click to Show/Hide
2 Prolactin signaling pathway
3 Thyroid hormone signaling pathway
4 Endocrine and other factor-regulated calcium reabsorption
5 Proteoglycans in cancer
NetPath Pathway FSH Signaling Pathway Click to Show/Hide
2 EGFR1 Signaling Pathway
3 RANKL Signaling Pathway
Pathway Interaction Database Regulation of nuclear SMAD2/3 signaling Click to Show/Hide
2 Signaling events mediated by HDAC Class II
3 Plasma membrane estrogen receptor signaling
4 LKB1 signaling events
5 Regulation of Telomerase
6 ATF-2 transcription factor network
7 AP-1 transcription factor network
8 FOXM1 transcription factor network
9 Validated nuclear estrogen receptor alpha network
10 Signaling mediated by p38-alpha and p38-beta
11 FOXA1 transcription factor network
Reactome Nuclear signaling by ERBB4 Click to Show/Hide
2 Nuclear Receptor transcription pathway
WikiPathways Estrogen signaling pathway Click to Show/Hide
2 Nuclear Receptors Meta-Pathway
3 Estrogen Receptor Pathway
4 Signaling by ERBB4
5 JAK/STAT
6 Integrated Pancreatic Cancer Pathway
7 Leptin signaling pathway
8 miR-targeted genes in muscle cell - TarBase
9 Integrated Breast Cancer Pathway
10 Nuclear Receptors
References
Reference 1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Reference 2 In vitro mechanism of action for the cytotoxicity elicited by the combination of epigallocatechin gallate and raloxifene in MDA-MB-231 cells. Oncol Rep. 2010 Sep;24(3):779-85.
Reference 3 Apoptosis induction in human breast cancer cell lines by synergic effect of raloxifene and resveratrol through increasing proapoptotic genes. Life Sci. 2018 Jul 15;205:45-53.
Reference 4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 620).
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