Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C17H20NO3.Na |
| Molecular Weight | 309.3354 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].CCC1=CC=CC2=C1NC3=C2CCO[C@]3(CC)CC([O-])=O
InChI
InChIKey=OYVVSFKYBAVZJZ-UNTBIKODSA-M
InChI=1S/C17H21NO3.Na/c1-3-11-6-5-7-12-13-8-9-21-17(4-2,10-14(19)20)16(13)18-15(11)12;/h5-7,18H,3-4,8-10H2,1-2H3,(H,19,20);/q;+1/p-1/t17-;/m1./s1
R-etodolac (SDX-101) is the non-cyclooxygenase 2-inhibiting R-enantiomer of the non-steroid anti-inflammatory drug etodolac (1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid). The absolute configuration of the enantiomer is R-(-)-etodolac. R-etodolac specifically bound retinoid X receptor (RXRalpha), inhibited RXRalpha transcriptional activity, and induced its degradation by a ubiquitin and proteasome-dependent pathway. In addition R-etodolac can disrupt the beta-catenin signaling pathway. R-etodolac exerts antineoplastic properties. R-etodolac was in phase 2 studies for the treatment of hematologic malignancies however development was discontinued.
Originator
Sources: http://adisinsight.springer.com/drugs/800016689 | http://en.pharmacodia.com/web/drug/1_5430.html
Curator's Comment: R-etodolac originally developed by Myriad Genetics, licensed to Salmedix (Division of Teva Pharmaceutical Industries Ltd.)
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
85.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18094935 |
1200 mg 2 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
ETODOLAC, (R)- plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
106.4 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18094935 |
2400 mg 2 times / day multiple, oral dose: 2400 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
ETODOLAC, (R)- plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
543.3 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18094935 |
1200 mg 2 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
ETODOLAC, (R)- plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
768.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18094935 |
2400 mg 2 times / day multiple, oral dose: 2400 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
ETODOLAC, (R)- plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
5.76 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18094935 |
1200 mg 2 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
ETODOLAC, (R)- plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
4.94 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18094935 |
2400 mg 2 times / day multiple, oral dose: 2400 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
ETODOLAC, (R)- plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| likely | ||||
| likely | ||||
| likely | ||||
| likely | ||||
| major | ||||
| minor | ||||
| minor | ||||
| minor | ||||
| minor | ||||
| minor | ||||
| minor | ||||
| minor | ||||
| minor | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Resolution of etodolac and antiinflammatory and prostaglandin synthetase inhibiting properties of the enantiomers. | 1983 Dec |
|
| Pharmacokinetic difference between S-(+)- and R-(-)-etodolac in rats. | 2004 Aug |
|
| SDX-101, the R-enantiomer of etodolac, induces cytotoxicity, overcomes drug resistance, and enhances the activity of dexamethasone in multiple myeloma. | 2005 Jul 15 |
|
| Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
Sample Use Guides
Phase 2, multi-center, open label, randomized clinical study for the treatment chronic lymphocytic leukaemia: R-etodolac 600mg tablets + chlorambucil 2mg tablets for 24-26 weeks
Route of Administration:
Oral
R-etodolac induced significant cytotoxicity in MM.1S, U266, RPMI8226, INA-6, and OPM1 MM cell lines with IC50 of 0.49, 1.06, 0.54, 0.22, and 0.47 mM, respectively. R-etodolac also triggers cytotoxicity, with IC50 of 0.62, 0.76 and 0.62 mM, respectively, in Dex-resistant MM.1R, Dox-resistant RPMI-Dox40, and bortezomib-resistant DHL4 cells32. Importantly, R-etodolac does not induce cytotoxicity in PBMCs from 3 healthy volunteers with concentrations as high as 2.5 mM
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101602496
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2V61D87073
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150975-87-4
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SUBSTANCE RECORD
