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

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

R-etodolac, RAK-593, SDX 101

+ [1]

Target

CTNNB1 x NF-κB x PPARγ

Action

inhibitors, agonists

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 DiseasesHemic and Lymphatic Diseases+ [1]

Active Indication-

Inactive Indication

Chronic Lymphocytic LeukemiaProstatic CancerRefractory Multiple Myeloma

Originator Organization

Salmedix, Inc.

Active Organization-

Inactive Organization

Cephalon, Inc.

Salmedix, Inc.

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

RegulationOrphan Drug (United States)

Login to view timeline

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.

EUCTR2004-000440-24-SE

/ Not yet recruitingNot Applicable

A Randomized, Multi-Center, Phase II Study to Investigate the Safety and Efficacy of SDX-101 (R-etodolac) in Combination with Chlorambucil, and that of Chlorambucil alone, in Patients with Chronic Lymphocytic Leukemia (CLL) - --

Start Date24 Aug 2004

Sponsor / Collaborator

Cephalon (UK) Ltd.

100 Clinical Results associated with (R)-Etodolac

Login to view more data

100 Translational Medicine associated with (R)-Etodolac

Login to view more data

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

Login to view more data

94

Literatures (Medical) associated with (R)-Etodolac

13 Aug 2022·MOLECULAR SIMULATION

Structure-Based Virtual Screening, Molecular Docking, Molecular Dynamics Simulation and Pharmacokinetic modelling of Cyclooxygenase-2 (COX-2) inhibitor for the clinical treatment of Colorectal Cancer

Author: Singh, Sanjeev Kumar ; Abdalla, Mohnad ; Chopra, Ishita ; Prajapati, Leena ; Sharma, Megha ; Hussain, Tajamul ; Albogami, Sarah ; Soni, Lovely ; Nayarisseri, Anuraj ; Shaheen, Uzma ; Madhavi, Maddala ; Sikarwar, Mayank Singh ; Bhrdwaj, Anushka ; Yadav, Manasi

Colorectal cancer is the third most frequent cause of cancer worldwide and is more prevalent in older individuals of all ages.The recent statistics from World Health Organization (WHO) on cancer accounted for 1.93 million new cases of colorectal cancer alone, in 2020[1].The exact cause of this disease is still unknown; however, obesity, sedentary lifestyle, and changed food consumption habit are thought to be driving forces.Earlier clin. studies have found non-steroidal anti-inflammatory drugs (NSAIDs) to be potent in treating colorectal cancer by inhibiting cyclooxygenase enzyme, and further research ascertained cyclooxygenase-2 gene (COX-2) inhibitors to be the most effective chemotherapy treatment.The aim of this study is to find the most effective inhibitor with a superior affinity against COX-2 protein and its pharmacol. profile.The pre-established compound, parecoxib (PubChem ID: 119828) was taken up for Structure-based Virtual Screening to identify a novel compound (PubChem ID: 10151468) that has a strong binding affinity than the established compoundAddnl., the comparative studies of both the screened and established compounds were examined using the MD simulation approach to confirm structural stability.Our conclusion suggests that the virtual screened compound (PubChem ID: 10151468) could be a potential therapeutic for the treatment of colorectal cancer.

01 Jul 2022·Biochemistry and biophysics reports

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

Article

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

26 May 2022·Journal of medicinal chemistryQ1 · MEDICINE

Biophysical Survey of Small-Molecule β-Catenin Inhibitors: A Cautionary Tale

Q1 · MEDICINE

Review

Author: McCoy, Michael A. ; Hoogewijs, Kurt ; Wells, Neil ; Baud, Matthias G. J. ; Spicer, Dominique ; Fiedler, Marc

The canonical Wingless-related integration site signaling pathway plays a critical role in human physiology, and its dysregulation can lead to an array of diseases. β-Catenin is a multifunctional protein within this pathway and an attractive yet challenging therapeutic target, most notably in oncology. This has stimulated the search for potent small-molecule inhibitors binding directly to the β-catenin surface to inhibit its protein-protein interactions and downstream signaling. Here, we provide an account of the claimed (and some putative) small-molecule ligands of β-catenin from the literature. Through in silico analysis, we show that most of these molecules contain promiscuous chemical substructures notorious for interfering with screening assays. Finally, and in line with this analysis, we demonstrate using orthogonal biophysical techniques that none of the examined small molecules bind at the surface of β-catenin. While shedding doubts on their reported mode of action, this study also reaffirms β-catenin as a prominent target in drug discovery.

100 Deals associated with (R)-Etodolac

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	(R)-Etodolac	-	-

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Chronic Lymphocytic Leukemia	Phase 2	France	Cephalon, Inc.	01 Sep 2004
Chronic Lymphocytic Leukemia	Phase 2	Germany	Cephalon, Inc.	01 Sep 2004
Chronic Lymphocytic Leukemia	Phase 2	Poland	Cephalon, Inc.	01 Sep 2004
Chronic Lymphocytic Leukemia	Phase 2	Sweden	Cephalon, Inc.	01 Sep 2004
Chronic Lymphocytic Leukemia	Phase 2	United Kingdom	Cephalon, Inc.	01 Sep 2004
Refractory Multiple Myeloma	Phase 2	United States	Cephalon, Inc.	01 Feb 2002
Prostatic Cancer	Preclinical	United States	Salmedix, Inc.	-