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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

Description

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

CNS Penetrant
2554
Curator's Comment: R-etodolac is CNS penetrant in animals. No human data available.

Originator

Myriad Genetics
2
Curator's Comment: R-etodolac originally developed by Myriad Genetics, licensed to Salmedix (Division of Teva Pharmaceutical Industries Ltd.)

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 200.0 µM [IC50]
Inhibitor
8297
 200.0 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

inhibitor
1587
substrate
1037

inhibitor
1767
substrate
1217

inhibitor
1852

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1524

CYP2C19
1478
UGT1A4
347

CYP2B6
664

UGT1A10
291

UGT2B7
389

CYP1A2
1054

CYP2C8
693

UGT2B15
203

UGT1A3
422

UGT1A8
283

CYP2A6
543

UGT1A7
236

UGT1A6
307

CYP2C19
991

UGT1A1
418

CYP2E1
667

UGT1A9
380

P-gp
1537
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1692
 no
CYP2C19
1553
 no
CYP2C9
1819
 no
CYP2D6
1891
 no
CYP3A4
1925
 no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
UGT1A3
422
 likely
UGT1A6
307
 likely
UGT1A9
380
 likely
UGT2B7
389
 likely
CYP2C9
1037
 major
CYP1A2
1054
 minor
CYP2A6
543
 minor
CYP2B6
664
 minor
CYP2C19
991
 minor
CYP2C8
693
 minor
CYP2D6
1217
 minor
CYP2E1
667
 minor
CYP3A4
1737
 minor
P-gp
1537
 no
UGT1A1
418
 no
UGT1A10
291
 no
UGT1A4
347
 no
UGT1A7
236
 no
UGT1A8
283
 no
UGT2B15
203
 no
PubMed

PubMed

TitleDatePubMed
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
Patents

Patents

JP2002538142A
8
JP2002544210A
89
JP2003507415A
33
JP2003529542A
6
JP2004510705A
4
JP2008201702A
6
JP2008519861A
32
JP2009525778A
32
JP2011524416A
138
JP4756823B2
22
JP4787165B2
101
US20060166947
2
US7105560
2
WO2007084853A2
2

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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
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
ACTIVE MOIETY
Structure of ETODOLAC, (R)-
NIH
NCATS
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ACCESSIBILITY
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