Glenmark Pharmaceuticals Limited · PTGS2 · Small Molecule
diacerein + aceclofenac is a small molecule developed by Glenmark Pharmaceuticals Limited. It is approved for therapeutic indications via oral (po).
| Company | Glenmark Pharmaceuticals Limited |
| Drug Class | Small Molecule |
| Molecular Target | PTGS2 |
| Route | Oral (PO) |
| Status | Approved |
diacerein + aceclofenac acts on 1 molecular target:
| PTGS2 | prostaglandin-endoperoxide synthase 2 (GRIPGHS, hCox-2) |
diacerein + aceclofenac is developed for 1 unique indication across 1 therapeutic area.
| Therapeutic Area | Condition | Phase |
|---|---|---|
| Musculoskeletal and connective tissue disorders | Musculoskeletal pain | ✓ Approved |
Chen Guixin G, Li Qin Q, Yu Chen C, Liu Hao H et al.
The development of multiple drugs for the synergistic osteoarthritis (OA) therapy is essential, particularly in light of the limited efficacy of existing clinical interventions. However, the poor bioavailability and systemic toxicity of hydrophobic drugs and their incompatibility with hydrophilic components largely hindered the co-delivery of multi-drugs. In this study, we present a dynamic covalent assembly strategy within a hyaluronic acid (HA) matrix to fabricate cationic dipeptide-based carrier particle (CGCP/HA). This carrier is designed to encapsulate hydrophobic nonsteroidal anti-inflammatory drug (NSAID) celecoxib and IL-1β inhibitor diacerein via a one-step co-assembly method, facilitating targeted drug delivery and combination therapy for OA. The resulting particles demonstrated exceptional stability, injectability, and biocompatibility in vitro, while mitigating the adverse effects associated with conventional oral OA medications. In a rat OA model, intra-articular administration of these co-assembled materials significantly suppressed inflammatory cytokines (TNF-α, IL-1β, and PGE2) and demonstrated enhanced cartilage repair by integrating multiple functions of hydrophilic HA, supramolecular carriers, and hydrophobic drugs. This work established a simple strategy for co-assembly of biomolecules and hydrophobic drug molecules and holds significant clinical promise for the treatment of OA.
Thulasidhasan J J, Ibrahim P S Syed PSS, Rajendiran N N
The role of two different non-steroidal anti-inflammatory drugs, namely, mefenamic acid (MA) (2-[(2,3-dimethylphenyl)amino]benzoic acid) and aceclofenac (ACF) (2-[(2,6-dichlorophenyl)amino]phenyl acetoxyacetic acid), and their electrostatic interactions with bovine serum albumin (BSA) and adenine model systems have been studied. The binding affinity for drug formation depends primarily on the heterocyclic ring and functional groups. The hydrophobic interactions were also evaluated. The spectral properties of the interactions were investigated by UV-visible, fluorescence, FT-IR, cyclic voltammetry and molecular modelling methods. In addition, the Stern-Volmer plots for BSA and adenine with the drug molecules are shown. Moreover, the static quenching interaction, the binding constant (Ka) and the number of sites (n) have been determined. The binding efficiency is evaluated and compared on the basis of its E value. The free energy, van der Waals and hydrogen-bonding interaction values of BSA with the drugs are determined. In order to assess the electrochemical process, the scan rate is another important parameter, which has been determined by using cyclic voltammograms.
[This corrects the article DOI: 10.1155/2016/9507563.].
Habib Heba A HA, Heeba Gehan H GH, Abdel-Latif Rania R
Nephrotoxicity is one of the most significant therapeutic limitations of gentamicin (GM) antibiotics, strongly linked to oxidative stress and apoptotic pathways. In this study, diacerein (DIA), an antiarthritic agent with potent antioxidant and anti-inflammatory properties, was investigated for its renoprotective potential and underlying mechanisms in GM-induced nephrotoxicity. Rats received GM (100 mg/kg, i.p.) alone or with DIA (25 or 50 mg/kg) for 10 days. Kidney tissues were assessed for histological damage, oxidative stress, apoptotic and inflammatory markers, and key signaling pathway activities. Structural equation modeling (SEM) was performed to explore mechanistic interactions and biomarker predictive. In a dose-dependent manner, DIA mitigated renal histopathological disturbance and attenuated the imbalanced oxidative status in GM-challenged rats by reducing renal MDA levels, as well as stimulating catalase and SOD activities and Nrf2 protein expression. DIA also attenuated GM-induced inflammation and apoptosis by suppressing NF-κB and cleaved caspase-3 expression. DIA restoration of phosphorylated PI3K and AKT protein expression, suggesting activation of the PI3K/AKT/Nrf2/NF-κB signaling pathway. Principal component analysis (PCA) extracted one dominant component (PC1) as the antioxidant-oxidative stress axis, explaining over 90% of the total variance. SEM further supported a mechanistic framework wherein PI3K strongly influenced AKT, which upregulated Nrf2 (β = 0.66, p < 0.001) and, in turn, enhanced CAT and SOD (β = 0.86 and 0.83, p < 0.001). The model reinforces AKT-Nrf2-CAT axis as a critical pathway modulating caspase-dependent apoptosis. DIA exhibits renal protection in GM-induced nephrotoxicity mainly through modulating PI3K/AKT/Nrf2 signaling pathways. PCA and SEM analyses provide novel mechanistic and diagnostic insights that enhance the translational potential of the findings.
Gujarathi Nayan A NA, Girase Rushikesh R, Sukhia Amey A, Aher Abhijeet A AA et al.
Chondroitin sulfate-functionalized ultra-deformable liposomes (CS-ACE-UDFLs) were developed for dual action, enhanced skin penetration and CD44-receptor-mediated precise delivery of drug. Optimization of critical parameters such as lipid concentration, sonication time, and edge activator concentration executed by Box-Behnken design. DLS particle size analyzer revealed nano-vesicle size (229.6 ± 7.95 nm), stable negative zeta potential (-41.30 ± 1.80 mV), high entrapment efficiency (73.53 ± 1.27%), and a low polydispersity index (0.253 ± 0.014) for CS-ACE-UDFLs. The encapsulation of aceclofenac confirmed through differential scanning calorimetry and X-ray diffraction studies. Surface characterization of CS-ACE-UDFLs with TEM analysis revealed a spherical morphology with a distinct chondroitin sulfate coating on the vesicle surface. In vitro release kinetics depicted the Korsmeyer-Peppas model, implying a complex release pattern, resulting from coupling of diffusion processes and matrix relaxation mechanisms. Enhanced drug release reported for CS-ACE-UDFLs (56.04% in 4 h, 91.80% in 8 h) post-incorporation edge activator compared to conventional liposomes (35.54% in 4 h, 68.51% in 8 h). The physicochemical parameters of CS-ACE-UDFLs were maintained during preliminary stability studies at 5°C. Confocal microscopy studies demonstrated a higher fluorescence intensity of functionalized ultradeformable liposomes hydrogel. Compared to ACE solution and ACE-UDFLs, CS-ACE-UDFLs showed superior anti-inflammatory activity in LPS-activated RAW 264.7 cells, characterized by enhanced cellular uptake and significantly lower levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α). In vivo studies on the CFA-induced arthritis rat model exhibited a significant reduction in paw volume and arthritis score (P < 0.0001) after treatment with the CS-ACE-UDFLs hydrogel system, indicating its potential in rheumatoid arthritis therapy.
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