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Molecular Medicine Reports Nov 2015Cyclin-dependent kinase 2 (CDK2) has been reported to be overexpressed in human colorectal cancer; it is responsible for the G1‑to‑S‑phase transition in the cell...
Cyclin-dependent kinase 2 (CDK2) has been reported to be overexpressed in human colorectal cancer; it is responsible for the G1‑to‑S‑phase transition in the cell cycle and its deregulation is a hallmark of cancer. The present study was the first to use idock, a free and open‑source protein‑ligand docking software developed by our group, to identify potential CDK2 inhibitors from 4,311 US Food and Drug Administration‑approved small molecular drugs with a re‑purposing strategy. Among the top compounds identified by idock score, nine were selected for further study. Among them, adapalene (ADA; CD271,6‑[3‑(1‑adamantyl)‑4‑methoxyphenyl]‑2‑naphtoic acid) exhibited the highest anti‑proliferative effects in LOVO and DLD1 human colon cancer cell lines. Consistent with the expected properties of CDK2 inhibitors, the present study demonstrated that ADA significantly increased the G1‑phase population and decreased the expression of CDK2, cyclin E and retinoblastoma protein (Rb), as well as the phosphorylation of CDK2 (on Thr‑160) and Rb (on Ser‑795). Furthermore, the anti‑cancer effects of ADA were examined in vivo on xenograft tumors derived from DLD1 human colorectal cancer cells subcutaneously inoculated in BALB/C nude mice. ADA (20 mg/kg orally) exhibited marked anti‑tumor activity, comparable to that of oxaliplatin (40 mg/kg), and dose‑dependently inhibited tumor growth (P<0.05), while combined administration of ADA and oxaliplatin produced the highest therapeutic effect. To the best of our knowledge, the present study was the first to indicate that ADA inhibits CDK2 and is a potential candidate drug for the treatment of human colorectal cancer.
Topics: Adapalene; Administration, Oral; Animals; Antineoplastic Agents; Cell Line, Tumor; Colorectal Neoplasms; Cyclin E; Cyclin-Dependent Kinase 2; Drug Combinations; Female; Gene Expression; High-Throughput Screening Assays; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Docking Simulation; Organoplatinum Compounds; Oxaliplatin; Phosphorylation; Retinoblastoma Protein; Tumor Burden; Xenograft Model Antitumor Assays
PubMed: 26398439
DOI: 10.3892/mmr.2015.4310 -
Thoracic Cancer Mar 2024Skin disorders are the most common side effect associated with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. It is important to manage...
BACKGROUND
Skin disorders are the most common side effect associated with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. It is important to manage skin lesions. Adapalene has been used to treat skin lesions caused by EGFR-TKIs in some cases. The aim of this study was to investigate the functional mechanism of adapalene in erlotinib-induced skin disorder.
METHODS
To analyze the effect of adapalene on skin rash, afatinib and adapalene were administered to mice. The relationship between the concentration of adapalene and skin disorders was also examined by analyzing AQP3 expression. A skin lesion model was experimentally established in human skin keratinocytes (HaCaT) by using erlotinib with TNF-α and IL-1β. We used qRT-PCR to analyze chemokine-induced inflammation and western blotting to analyze the effects of adapalene on the NF-κB signaling pathway. Antimicrobial peptides and adhesion factors were also examined using qRT-PCR.
RESULTS
Mice administered 0.01% adapalene had less skin inflammation than mice treated with afatinib alone. The expression level of AQP3 decreased in an adapalene concentration-dependent manner. The mRNA levels of proinflammatory cytokines such as CCL2 and CCL27 in HaCaT cells were significantly reduced by adapalene. The expression of an antimicrobial peptide, hBD3, was upregulated after adapalene treatment. Adhesion factors, such as E-cadherin, were significantly downregulated by EGFR-TKI and significantly upregulated by adapalene treatment. Western blot analysis suggested that erlotinib-induced phosphorylation of p65 was decreased by adapalene.
CONCLUSION
We suggest that adapalene may be a possible treatment option for skin disorders induced by EGFR-TKIs.
Topics: Humans; Animals; Mice; Afatinib; Erlotinib Hydrochloride; Adapalene; ErbB Receptors; Skin Diseases; Inflammation; Protein Kinase Inhibitors; Lung Neoplasms
PubMed: 38379420
DOI: 10.1111/1759-7714.15249 -
Clinical, Cosmetic and Investigational... 2023We aim to evaluate the effectiveness and tolerability of a sunscreen formulation containing licochalcone A (LicA) and L-carnitine (LC) as an adjuvant to adapalene in the...
Efficacy and Tolerability of a Sunscreen Containing Licochalcone a and L-Carnitine as an Adjunct to Retinoids in the Management of Acne and Post-Acne Pigmentation Among Malaysian Patients.
PURPOSE
We aim to evaluate the effectiveness and tolerability of a sunscreen formulation containing licochalcone A (LicA) and L-carnitine (LC) as an adjuvant to adapalene in the management of acne and post-acne pigmentation (PAH).
PATIENTS AND METHODS
A randomized, double-blind, active comparator-controlled trial of 51 patients aged 18 years or older with a clinical diagnosis of mild-to-moderate acne vulgaris was conducted at the Hospital Sultan Abdul Aziz Shah, Universiti Putra Malaysia. The efficacy and tolerability of once-daily adapalene 1.0% were assessed during the 2-week run-in period. Subsequently, patients were randomized to receive either an add-on investigational LicA-containing sunscreen or niacinamide-containing comparator sunscreen every 4 hourly during daytime for 4 weeks. Patients were followed up at Weeks 2 and 4 to assess for improvement in acne severity, PAH, calorimetric parameters and cutaneous tolerability.
RESULTS
Two weeks of adapalene usage significantly improved acne severity; however, up to 52% of patients experienced dryness, burning and stinging. Adding LicA-containing or comparator sunscreens was associated with further improvement in acne severity, PAH and calorimetric parameters at the study endpoint. No significant differences in the cutaneous tolerability profiles were observed between treatment groups. Notably, significantly fewer patients receiving LicA-containing sunscreen developed scaliness at Week 4 compared with those in the comparator group. In addition, more patients receiving LicA-containing sunscreen reported less dryness, burning and stinging reactions than the comparator group. Importantly, more patients receiving LicA-containing sunscreen agreed that their treatment led to excellent improvement than the comparator group; of note, one patient reported that their condition worsened with the receipt of the comparator product.
CONCLUSION
The concurrent use of LicA-containing sunscreen with adapalene may improve the cutaneous tolerance to adapalene among Malaysian patients.
PubMed: 38152154
DOI: 10.2147/CCID.S422898 -
JPMA. the Journal of the Pakistan... Oct 2023
Topics: Humans; Adapalene; Acne Vulgaris; Anti-Inflammatory Agents, Non-Steroidal; Melanoma; Gels; Treatment Outcome; Dermatologic Agents
PubMed: 37876097
DOI: 10.47391/JPMA.8438 -
Drug Safety Mar 2024In refining drug safety signals, defining the object of study is crucial. While research has explored the effect of different event definitions, drug definition is often...
INTRODUCTION
In refining drug safety signals, defining the object of study is crucial. While research has explored the effect of different event definitions, drug definition is often overlooked. The US FDA Adverse Event Reporting System (FAERS) records drug names as free text, necessitating mapping to active ingredients. Although pre-mapped databases exist, the subjectivity and lack of transparency of the mapping process lead to a loss of control over the object of study.
OBJECTIVE
We implemented the DiAna dictionary, systematically mapping individual free-text instances to their corresponding active ingredients and linking them to the World Health Organization Anatomical Therapeutic Chemical (WHO-ATC) classification.
METHODS
We retrieved all drug names reported to the FAERS (2004-December 2022). Using existing vocabularies and string editing, we automatically mapped free text to ingredients. We manually revised the mapping and linked it to the ATC classification.
RESULTS
We retrieved 18,151,842 reports, with 74,143,411 drug entries. We manually checked the first 14,832 terms, up to terms occurring over 200 times (96.88% of total drug entries), to 6282 unique active ingredients. Automatic unchecked translations extend the standardization to 346,854 terms (98.94%). The DiAna dictionary showed a higher sensitivity compared with RxNorm alone, particularly for specific drugs (e.g., rimegepant, adapalene, drospirenone, umeclidinium). The most prominent drug classes in the FAERS were immunomodulating (37.40%) and neurologic drugs (29.19%).
CONCLUSION
The DiAna dictionary, as a dynamic open-source tool, provides transparency and flexibility, enabling researchers to actively shape drug definitions during the mapping phase. This empowerment enhances accuracy, reproducibility, and interpretability of results.
Topics: United States; Humans; Adverse Drug Reaction Reporting Systems; Drug-Related Side Effects and Adverse Reactions; Reproducibility of Results; Software; United States Food and Drug Administration
PubMed: 38175395
DOI: 10.1007/s40264-023-01391-4 -
Indian Journal of Dermatology Jul 2014A combination of topical retinoid and antibacterial therapy is often advocated for acne to enhance therapeutic efficacy.
Efficacy and tolerability of topical fixed combination of nadifloxacin 1% and adapalene 0.1% in the treatment of mild to moderate acne vulgaris in Indian patients: a multicenter, open-labelled, prospective study.
BACKGROUND
A combination of topical retinoid and antibacterial therapy is often advocated for acne to enhance therapeutic efficacy.
AIMS
A preliminary study to evaluate the efficacy and tolerability of a topical fixed combination of nadifloxacin (1%) and adapalene (0.1%) in the treatment of mild to moderate acne in Indian patients.
MATERIALS AND METHODS
This was an open-labeled, phase 3 non-randomized, non-comparative study conducted at five centers (Ahmedabad, Nagpur, Thane, Bangalore, and Mumbai) across India. Of 119 enrolled patients with mild to moderate acne, 117 patients were evaluated at the end of the study for efficacy parameters. A fixed combination of nadifloxacin (1%) and adapalene (0.1%) topical gel was applied at the affected area once at night for a period of 8 weeks. Reduction in the total, inflammatory and non-inflammatory lesion counts from the baseline, investigator global assessment (IGA) and reduction in the severity of acne as per combined acne severity classification were the primary efficacy variables measured at 2 weeks, 4 weeks, and 8 weeks.
RESULTS
Overall, 98.3% patients showed a statistically significant progressive reduction in non-inflammatory lesion counts, inflammatory lesion counts, and total lesion counts over the study duration. By the end of 8 weeks, 75% of the patients had their global assessment scores approaching to normal healthy skin score. The adverse events were mild to moderate in severity.
CONCLUSION
This preliminary study shows that a fixed combination of 1% nadifloxacin and 0.1% adapalene topical gel could be an effective and well-tolerated option for the treatment of mild to moderate acne vulgaris. However, further well-controlled, randomized and comparative evaluation of this combination is necessary.
PubMed: 25071260
DOI: 10.4103/0019-5154.135492 -
Clinical, Cosmetic and Investigational... 2011Acne vulgaris is a chronic disease with several pathogenic factors. Multiple medications are typically used that can lead to nonadherence and treatment failure....
BACKGROUND
Acne vulgaris is a chronic disease with several pathogenic factors. Multiple medications are typically used that can lead to nonadherence and treatment failure. Combination medications target multiple pathways of acne formation and may offer therapeutic benefit.
PURPOSE
To explore the efficacy and tolerability of combination retinoid plus antimicrobial treatments in acne vulgaris.
METHODS
A PubMed and Google search was conducted for combination therapies of clindamycin and tretinoin, with secondary analysis of related citations and references. Similar searches were completed for the combination medications of benzoyl peroxide plus clindamycin or erythromycin, and for the combination therapy of adapalene and benzoyl peroxide.
RESULTS
Combination clindamycin phosphate and tretinoin gel was found to be more efficacious than monotherapy of either drug or its vehicle for acne, including inflammatory acne, and has a greater onset of action than either drug alone. Clindamycin phosphate and tretinoin gel was well-tolerated, and adherence to its use exceeded that of using both medications in separate formulations. Benzoyl peroxide-containing combination medications with clindamycin or erythromycin were both more effective in the treatment of acne than either drug alone. Both medications were well-tolerated, with dry skin being the most common adverse effect.
CONCLUSIONS
Combination medications have superior efficacy and adherence, and have a similar tolerability profile compared with monotherapy of its components. Several studies have found antibiotic-containing combination products with a retinoid effective for acne. The use of antibiotic-containing combination medications for acne can lead to bacterial resistance. Due to this potential for bacterial resistance, benzoyl peroxide treatments are also recommended in combination with a retinoid.
PubMed: 21760743
DOI: 10.2147/CCID.S13873 -
American Family Physician Jan 2000Acne is a common problem in adolescents and young adults. The disorder is caused by abnormal desquamation of follicular epithelium that results in obstruction of the... (Review)
Review
Acne is a common problem in adolescents and young adults. The disorder is caused by abnormal desquamation of follicular epithelium that results in obstruction of the pilosebaceous canal. This obstruction leads to the formation of comedones, which can become inflamed because of overgrowth of Propionibacterium acnes. Topical retinoids such as tretinoin or adapalene are effective in many patients with comedonal acne. Patients with inflammatory lesions benefit from treatment with benzoyl peroxide, azelaic acid or topical antibiotics. Frequently, the use of comedonal and antibacterial agents is required.
Topics: Acne Vulgaris; Administration, Topical; Adolescent; Adult; Anti-Bacterial Agents; Anti-Infective Agents, Local; Benzoyl Peroxide; Dermatologic Agents; Dicarboxylic Acids; Drug Therapy, Combination; Humans; Keratolytic Agents; Patient Education as Topic; Pharmaceutical Vehicles; Retinoids; Salicylic Acid; Sulfacetamide
PubMed: 10670502
DOI: No ID Found -
Antimicrobial Agents and Chemotherapy Apr 2023Acne vulgaris is a complex skin disease involving infection by Cutibacterium acnes, inflammation, and hyperkeratinization. We evaluated the activity of the retinoid...
Acne vulgaris is a complex skin disease involving infection by Cutibacterium acnes, inflammation, and hyperkeratinization. We evaluated the activity of the retinoid 6-[3-(adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and 16 other retinoid analogs as potential anti- compounds and found that CD437 displayed the highest antimicrobial activity with an MIC against (ATCC 6919 and HM-513) of 1 μg/mL. CD437 demonstrated an MBC of 2 μg/mL compared to up to 64 μg/mL for the retinoid adapalene and up to 16 μg/mL for tetracycline, which are commonly used clinically to treat acne. Membrane permeability assays demonstrated that exposure of ATCC 6919 to CD437 damaged the integrity of ATCC 6919 bacterial membranes, and this finding was confirmed with scanning electron microscopy. Additionally, CD437 downregulated the expression of ATCC 6919 virulence factors, including the genes encoding Christie-Atkins-Munch-Petersen factor 1 (CAMP1), CAMP2, glycerol-ester hydrolase B (GehB), sialidase B, and neuraminidase. In a mouse skin infection model of ATCC 6919, topical treatment with CD437 ameliorated skin lesions and reduced the bacterial burden ( < 0.001). In human NHEK primary cells, CD437 reduced the transcriptional levels of the coding genes for inflammatory cytokines (interleukin-1α, ~10-fold; interleukin-6, ~20-fold; interleukin-8, ~30-fold; and tumor necrosis factor-alpha, ~6-fold) and downregulated the transcriptional levels of (~10-fold), (~4-fold), and (~2-fold), indicating that CD437 can diminish inflammation and hyperkeratinization. In summary, CD437 deserves further attention for its dual function as a potential acne therapeutic that potentially acts on both the pathogen and the host.
Topics: Mice; Animals; Humans; Retinoids; Acne Vulgaris; Cytokines; Anti-Bacterial Agents; Inflammation; Propionibacterium acnes
PubMed: 36943064
DOI: 10.1128/aac.01679-22 -
Indian Journal of Dermatology,... 2012Acne vulgaris is a very common skin disease with a significant detrimental effect on the quality of life of the patients. (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of a nano-emulsion gel formulation of adapalene 0.1% and clindamycin 1% combination in acne vulgaris: a randomized, open label, active-controlled, multicentric, phase IV clinical trial.
BACKGROUND
Acne vulgaris is a very common skin disease with a significant detrimental effect on the quality of life of the patients.
AIMS
To assess the comparative efficacy and safety of a nano-emulsion gel formulation of adapalene and clindamycin combination with its conventional formulation in the treatment of acne vulgaris of the face. It was a prospective, randomized, open label, active-controlled, multicentric, clinical trial.
METHODS
Eligible patients suffering from acne vulgaris of the face were randomized to receive once-daily treatment with a nano-emulsion gel or conventional gel formulation of adapalene 0.1% and clindamycin (as phosphate) 1% combination for 12 weeks. Total, inflammatory and noninflammatory lesion counts, with grading of acne severity were carried out on a monthly basis. Safety assessments were done to determine the comparative local and systemic tolerability. Two-tailed significance testing was carried out with appropriate statistical tests, and P-values < 0.05 were considered as significant.
RESULTS
209/212 patients enrolled in the study were eligible for efficacy and safety assessments in both nano-emulsion gel (118/119 patients) and conventional gel (91/93 patients) groups. Significantly better reductions in total (79.7% vs. 62.7%), inflammatory (88.7% vs. 71.4%) and noninflammatory (74.9% vs. 58.4%) lesions were reported with the nano-emulsion gel as compared to the conventional gel (P < 0.001 for all). Mean acne severity score also reduced significantly more with the nano-emulsion formulation (1.9 ± 0.9 vs. 1.4 ± 1.0; P < 0.001) than the comparator. Significantly lower incidence and lesser intensity of adverse events like local irritation (4.2% vs. 19.8%; P < 0.05) and erythema (0.8% vs. 9.9%; P < 0.05) were recorded with the nano-emulsion gel.
CONCLUSIONS
The nano-emulsion gel formulation of adapalene and clindamycin combination appears to be more efficacious and better tolerated than the conventional formulation for the treatment of acne vulgaris in Indian patients. Further studies can elucidate the comparative treatment benefits of this nano-emulsion gel formulation.
Topics: Acne Vulgaris; Adapalene; Adolescent; Adult; Anti-Bacterial Agents; Clindamycin; Dermatologic Agents; Drug Combinations; Emulsions; Female; Gels; Humans; Male; Nanotechnology; Naphthalenes; Treatment Outcome; Young Adult
PubMed: 22772617
DOI: 10.4103/0378-6323.98077