Delving into the Latest Updates on (R)-Etodolac with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

R-etodolac

+ [1]

Target

CTNNB1 x NF-κB x PPARγ

Mechanism

CTNNB1 inhibitors(Catenin beta 1 inhibitors), NF-κB inhibitors(Nuclear factor NF-kappa-B complex inhibitors), PPARγ agonists(Peroxisome proliferator-activated receptor γ agonists)

Therapeutic Areas

NeoplasmsImmune System DiseasesCardiovascular Diseases+ [2]

Active Indication-

Inactive Indication

Chronic Lymphocytic LeukemiaMultiple MyelomaProstatic Cancer

Originator Organization

Salmedix, Inc.

Active Organization-

Inactive Organization

Salmedix, Inc.

Cephalon, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

RegulationOrphan Drug (US)

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Structure/Sequence

Molecular FormulaC17H21NO3

InChIKeyNNYBQONXHNTVIJ-QGZVFWFLSA-N

CAS Registry87226-41-3

This is a Phase 2, multi-center, open label, randomized clinical study to evaluate the safety and efficiency of SDX-101 in combination with chlorambucil (CLB) and chlorambucil alone in Chronic Lymphocytic Leukaemia (CLL) patients. The study treatment period will be approximately 24-26 weeks with a follow-up period of approximately 8 weeks. Following the end of treatment, patients with a confirmed complete response, partial response or stable disease will be followed for up to 2 years to assess time to disease progression. Approximately 80 patients with documented diagnosis of B-cell CLL by standard clinical and immunophenotyping criteria will be enrolled into the SDX-101-03 study. This study is being conducted in the following European countries: France, Germany, Poland, Sweden and the United Kingdom.

Start Date01 Sep 2004

Sponsor / Collaborator

Cephalon, Inc.

100 Clinical Results associated with (R)-Etodolac

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100 Translational Medicine associated with (R)-Etodolac

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100 Patents (Medical) associated with (R)-Etodolac

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37

Literatures (Medical) associated with (R)-Etodolac

01 Jul 2022·Biochemistry and Biophysics Reports

R-etodolac is a more potent Wnt signaling inhibitor than enantiomer, S-etodolac

Article

Author: Kang, Stephen ; Deng, Sophie X ; Ma, Chao ; Roberts, JoAnn S ; Robertson, Sarah Y T ; Han, Christiana S ; Zheng, Jie J

Etodolac is an FDA-approved nonsteroidal anti-inflammatory drug (NSAID) used to treat a variety of inflammatory diseases. The drug is administered as a racemate (50/50 mixture of R- and S- enantiomers), however, studies have shown that the two enantiomers have distinct biologic and pharmacokinetic differences. Wnt signaling, which plays key roles in cell proliferation, polarity, and differentiation, has been shown to be inhibited by R-etodolac; however, comparative analyses of R- and S-etodolac in this function have not been conducted. We used in silico molecular docking and TOPflash functional biologic assays to compare R- and S-enantiomers effect on Wnt signaling inhibition. Further, we used a cultivated limbal stem epithelial cell (cLSCs) model to investigate enantiospecific changes in the colony-forming efficiency (CFE) of cLSCs. The data shows that R-etodolac is a more potent inhibitor of Wnt signaling. In addition, consistently, while both enantiomers demonstrate a dose-dependent decrease in CFE of cLSCs, R-etodolac is a more potent inhibitor.

01 Dec 2017·The Journal of the Association of Physicians of India

Association of Physicians of India: Position Statement on Role of Chirally Pure Molecules in Clinical Practice.

Article

Author: Nadkar, Milind Y ; Mishra, Sundeep ; Ponde, C K ; Kalra, Sanjay ; Das, A K ; Sahay, Manisha ; Bansode, B R ; Tiwaskar, Shilpa ; Prabhoo, Ram ; Vora, Agam ; Balhara, Yatan Pal Singh ; Jacob, Jubbin ; Dhamija, Puneet ; S, Balakrishnan ; Narasingan, S N ; Gupta, Y K ; Bajaj, Sarita ; Sahay, R K ; Sathyamurthy, I ; Dutta, Anjanlal ; Shah, Siddharth N ; Aggarwal, Sameer ; Tiwaskar, Mangesh

Chirally pure molecules or enantiomers are non-superimposable mirror images of each other with a chiral center (such as carbon, sulphur, nitrogen or phosphorous atom). An equimolar mixture of enantiomers forms a racemate. Chirally pure molecules (single enantiomers) are important in the field of drug discovery as the drug targets such as enzymes and receptors are enantioselective in nature. Clinical studies have demonstrated that chirally pure drugs exhibit different pharmacokinetic and metabolic profiles, reduced adverse events, improved safety profiles and similar therapeutic activity at lowered drug dosage as compared with the racemate in many therapeutic areas. However, since there is a low level of awareness on the advantages of chirally pure molecules among clinicians, pharmacists and patients in India, the Association of Physicians of India (API) developed this position statement to increase awareness on the concept of chirality and the associated advantages of using chirally pure drugs in certain therapeutic areas to maximize patient outcomes. This includes the clinical evidence associated with single enantiomers such as S-metoprolol, S-amlodipine, esomeprazole, escitalopram, levobupivacaine, cisatracurium, S-etodolac, dexketoprofen, levofloxacin in terms of efficacy and safety as compared with their racemates. In addition, the API also provides some tactical recommendations for clinicians, pharmacists, patients, regulatory body and pharmaceutical companies to increase awareness on chirally pure drugs and puts forth the need for expedited availability of chirally pure drugs in the Indian market.

01 Nov 2017·The AAPS JournalQ3 · MEDICINE

Development of an Enantioselective and Biomarker-Informed Translational Population Pharmacokinetic/Pharmacodynamic Model for Etodolac

Q3 · MEDICINE

Article

Author: Bulitta, Jürgen B ; Dalla Costa, Teresa ; de Miranda Silva, Carolina ; da Silva, Lucienir Maria ; Lanchote, Vera Lucia ; Rocha, Adriana ; Schmidt, Stephan ; Tozatto, Eduardo ; Donadi, Eduardo Antônio

Cyclooxygenase-2 (COX-2) isoform has a critical role in the development of pain. Inhibition of COX-2 in vitro serves as a biomarker for nonsteroidal anti-inflammatory drugs (NSAIDs). The NSAID concentrations yielding 80% COX-2 inhibition (IC₈₀) correlate with therapeutic doses to achieve analgesia across multiple COX-2 inhibitors. However, there are no time-course models relating COX-2 inhibition with decreased pain. This study aimed to characterize the relationship between NSAID concentrations, in vitro COX-2 inhibition, and acute pain decrease in humans over time by a translational approach using clinical pharmacokinetic and literature reported in vitro and clinical pharmacodynamic data. In a two-way cross-over study, eight healthy volunteers received 300 and 400 mg racemic etodolac, a preferential COX-2 inhibitor. R- and S-etodolac were determined by LC-MS/MS and simultaneously modeled. Literature in vitro IC₅₀ data for COX-2 inhibition by S-etodolac were used to fit adjusted pain score profiles from dental patients receiving etodolac. External model qualification was performed using published ibuprofen data. Etodolac absorption was highly variable due to gastric transit kinetics and low aqueous solubility. The disposition parameters differed substantially between enantiomers with a total clearance of 2.21 L/h for R-etodolac and 26.8 L/h for S-etodolac. Volume of distribution at steady-state was 14.6 L for R-etodolac and 45.8 L for S-etodolac. Inhibition of COX-2 by 78.1% caused a half-maximal pain decrease. The time-course of pain decrease following ibuprofen was successfully predicted via the developed translational model. This proposed enantioselective pharmacodynamic-informed approach presents the first quantitative time-course model for COX-2 induced pain inhibition in patients.

100 Deals associated with (R)-Etodolac

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic Lymphocytic Leukemia	Phase 2	FR	Cephalon, Inc.	01 Sep 2004
Chronic Lymphocytic Leukemia	Phase 2	SE	Cephalon, Inc.	01 Sep 2004
Chronic Lymphocytic Leukemia	Phase 2	GB	Cephalon, Inc.	01 Sep 2004
Chronic Lymphocytic Leukemia	Phase 2	DE	Cephalon, Inc.	01 Sep 2004
Chronic Lymphocytic Leukemia	Phase 2	PL	Cephalon, Inc.	01 Sep 2004
Multiple Myeloma	Phase 2	US	Cephalon, Inc.	01 Feb 2002
Prostatic Cancer	Phase 2	US	Salmedix, Inc.	-