U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C17H21NO3
Molecular Weight 287.3535
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ETODOLAC, (R)-

SMILES

CCC1=CC=CC2=C1NC3=C2CCO[C@]3(CC)CC(O)=O

InChI

InChIKey=NNYBQONXHNTVIJ-QGZVFWFLSA-N
InChI=1S/C17H21NO3/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)/t17-/m1/s1

HIDE SMILES / InChI

Molecular Formula C17H21NO3
Molecular Weight 287.3535
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

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.

CNS Activity

Curator's Comment: R-etodolac is CNS penetrant in animals. No human data available.

Originator

Curator's Comment: R-etodolac originally developed by Myriad Genetics, licensed to Salmedix (Division of Teva Pharmaceutical Industries Ltd.)

Approval Year

Targets

Targets

Conditions
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
85.1 μg/mL
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
543.3 μg × h/mL
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
5.76 h
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
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
OverviewDrug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
likely
likely
likely
likely
major
minor
minor
minor
minor
minor
minor
minor
minor
no
no
no
no
no
no
no
PubMed

PubMed

TitleDatePubMed
Resolution of etodolac and antiinflammatory and prostaglandin synthetase inhibiting properties of the enantiomers.
1983 Dec
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Patents

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
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:42:40 GMT 2023
Edited
by admin
on Fri Dec 15 15:42:40 GMT 2023
Record UNII
Y1RAH31T6K
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ETODOLAC, (R)-
Common Name English
(-)-ETODOLAC
Common Name English
R-ETODOLAC
Common Name English
(1R)-1,8-DIETHYL-1,3,4,9-TETRAHYDROPYRANO(3,4-B)INDOLE-1-ACETIC ACID
Systematic Name English
PYRANO(3,4-B)INDOLE-1-ACETIC ACID, 1,8-DIETHYL-1,3,4,9-TETRAHYDRO-, (1R)-
Common Name English
KS-1056
Code English
RAK-593
Code English
ETODOLAC, (-)-
Common Name English
SDX-101
Code English
(-)-(R)-ETODOLAC
Common Name English
PYRANO(3,4-B)INDOLE-1-ACETIC ACID, 1,8-DIETHYL-1,3,4,9-TETRAHYDRO-, (R)-
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 162702
Created by admin on Fri Dec 15 15:42:40 GMT 2023 , Edited by admin on Fri Dec 15 15:42:40 GMT 2023
Code System Code Type Description
CAS
147170-18-1
Created by admin on Fri Dec 15 15:42:40 GMT 2023 , Edited by admin on Fri Dec 15 15:42:40 GMT 2023
SUPERSEDED
SMS_ID
100000178237
Created by admin on Fri Dec 15 15:42:40 GMT 2023 , Edited by admin on Fri Dec 15 15:42:40 GMT 2023
PRIMARY
EPA CompTox
DTXSID60233938
Created by admin on Fri Dec 15 15:42:40 GMT 2023 , Edited by admin on Fri Dec 15 15:42:40 GMT 2023
PRIMARY
CAS
87226-41-3
Created by admin on Fri Dec 15 15:42:40 GMT 2023 , Edited by admin on Fri Dec 15 15:42:40 GMT 2023
PRIMARY
FDA UNII
Y1RAH31T6K
Created by admin on Fri Dec 15 15:42:40 GMT 2023 , Edited by admin on Fri Dec 15 15:42:40 GMT 2023
PRIMARY
CHEBI
60370
Created by admin on Fri Dec 15 15:42:40 GMT 2023 , Edited by admin on Fri Dec 15 15:42:40 GMT 2023
PRIMARY
ChEMBL
CHEMBL1716091
Created by admin on Fri Dec 15 15:42:40 GMT 2023 , Edited by admin on Fri Dec 15 15:42:40 GMT 2023
PRIMARY
CAS
848873-99-4
Created by admin on Fri Dec 15 15:42:40 GMT 2023 , Edited by admin on Fri Dec 15 15:42:40 GMT 2023
SUPERSEDED
PUBCHEM
667528
Created by admin on Fri Dec 15 15:42:40 GMT 2023 , Edited by admin on Fri Dec 15 15:42:40 GMT 2023
PRIMARY
Related Record Type Details
RACEMATE -> ENANTIOMER
Related Record Type Details
ACTIVE MOIETY