Drug repurposing in psoriasis, performed by reversal of disease-associated gene expression profiles

Ahmed, Faheem; Ho, Son Gi; Samantasinghar, Anupama; Memon, Fida Hussain; Rahim, Chethikkattuveli Salih Abdul; Soomro, Afaque Manzoor; Pratibha, .; Sunildutt, Naina; Kim, Kyung Hwan; Choi, Kyung Hyun

doi:10.1016/j.csbj.2022.10.046

Cited by 26 publications

(22 citation statements)

References 39 publications

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“…The field of cosmeceuticals targeting the skin is no exception: skin appearance is essential for self-esteem and quality of life, and therefore skincare products represent a huge market. In particular, cosmeceuticals are a hybrid category of skin care formulations that are halfway between cosmetics and pharmaceuticals and are rationally designed to target (pathological) physiological mechanisms to improve skin health and appearance [28][29][30].…”

Section: Discussionmentioning

confidence: 99%

Acenocoumarol, an Anticoagulant Drug, Prevents Melanogenesis in B16F10 Melanoma Cells

Han

Hyun

2023

Pharmaceuticals

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Hyperpigmentation can occur in abnormal skin conditions such as melanomas, as well as in conditions including melasma, freckles, age spots, seborrheic keratosis, and café-au-lait spots (flat brown spots). Thus, there is an increasing need for the development of depigmenting agents. We aimed to repurpose an anticoagulant drug as an effective ingredient against hyperpigmentation and apply cosmeceutical agents. In the present study, the anti-melanogenic effects of two anticoagulant drugs, acenocoumarol and warfarin, were investigated. The results showed that both acenocoumarol and warfarin did not cause any cytotoxicity and resulted in a significant reduction in intracellular tyrosinase activity and melanin content in B16F10 melanoma cells. Additionally, acenocoumarol inhibits the expression of melanogenic enzymes such as tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2, suppressing melanin synthesis through a cAMP-dependent, protein kinase (PKA)-dependent downregulation of microphthalmia-associated transcription factor (MITF), a master transcription factor in melanogenesis. Furthermore, anti-melanogenic effects were exerted by acenocoumarol through downregulation of the p38 and JNK signaling pathway and upregulation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthesis kinase-3β (GSK-3β) cascades. In addition, the β-catenin content in the cell cytoplasm and nucleus was increased by acenocoumarol through a reduction in the phosphorylated β-catenin (p-β-catenin content). Finally, we tested the potential of acenocoumarol for topical applications by conducting primary human skin irritation tests. Acenocoumarol did not induce any adverse reactions during these tests. Based on the results, it can be concluded that acenocoumarol regulates melanogenesis through various signaling pathways such as PKA, MAPKs, PI3K/Akt/GSK-3β, and β-catenin. These findings suggest that acenocoumarol has the potential to be repurposed as a drug for treating hyperpigmentation symptoms and could provide new insights into the development of therapeutic approaches for hyperpigmentation disorders.

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Section: Discussionmentioning

confidence: 99%

Acenocoumarol, an Anticoagulant Drug, Prevents Melanogenesis in B16F10 Melanoma Cells

Han

Hyun

2023

Pharmaceuticals

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“…Additionally, transcriptomics with morphological profiling was used to predict other synergistic toxicities. Overall, the study highlights the potential of liver organoids as a promising model for DILI risk prediction and emphasizes the need for further optimization and expansion to encompass patient genetic diversity (Ahmed et al, 2022f;Zhang et al, 2023).…”

Section: Toxicity and Organ On Chipmentioning

confidence: 94%

Revolutionizing drug development: harnessing the potential of organ-on-chip technology for disease modeling and drug discovery

et al. 2023

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The inefficiency of existing animal models to precisely predict human pharmacological effects is the root reason for drug development failure. Microphysiological system/organ-on-a-chip technology (organ-on-a-chip platform) is a microfluidic device cultured with human living cells under specific organ shear stress which can faithfully replicate human organ-body level pathophysiology. This emerging organ-on-chip platform can be a remarkable alternative for animal models with a broad range of purposes in drug testing and precision medicine. Here, we review the parameters employed in using organ on chip platform as a plot mimic diseases, genetic disorders, drug toxicity effects in different organs, biomarker identification, and drug discoveries. Additionally, we address the current challenges of the organ-on-chip platform that should be overcome to be accepted by drug regulatory agencies and pharmaceutical industries. Moreover, we highlight the future direction of the organ-on-chip platform parameters for enhancing and accelerating drug discoveries and personalized medicine.

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“…The drugs were ranked based on negative scoring to positive scoring, and the top 50 negative-scored drug perturbations were recorded for further analysis. These drugs were hypothesized to reverse the expression of the diseased genes (shown in Figure c) …”

Section: Methodsmentioning

confidence: 99%

“…These drugs were hypothesized to reverse the expression of the diseased genes (shown in Figure 1c). 31 2.5. Validating Prioritized Drug Candidates.…”

Section: Analysis Using Connectivity Mapmentioning

confidence: 99%

Integrating Transcriptomic and Structural Insights: Revealing Drug Repurposing Opportunities for Sporadic ALS

Sunildutt,

Ahmed,

Chethikkattuveli Salih

et al. 2024

ACS Omega

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Amyotrophic lateral sclerosis (ALS) is a progressive and devastating neurodegenerative disorder characterized by the loss of upper and lower motor neurons, resulting in debilitating muscle weakness and atrophy. Currently, there are no effective treatments available for ALS, posing significant challenges in managing the disease that affects approximately two individuals per 100,000 people annually. To address the urgent need for effective ALS treatments, we conducted a drug repurposing study using a combination of bioinformatics tools and molecular docking techniques. We analyzed sporadic ALS-related genes from the GEO database and identified key signaling pathways involved in sporadic ALS pathogenesis through pathway analysis using DAVID. Subsequently, we utilized the Clue Connectivity Map to identify potential drug candidates and performed molecular docking using AutoDock Vina to evaluate the binding affinity of short-listed drugs to key sporadic ALS-related genes. Our study identified Cefaclor, Diphenidol, Flubendazole, Fluticasone, Lestaurtinib, Nadolol, Phenamil, Temozolomide, and Tolterodine as potential drug candidates for repurposing in sporadic ALS treatment. Notably, Lestaurtinib demonstrated high binding affinity toward multiple proteins, suggesting its potential as a broad-spectrum therapeutic agent for sporadic ALS. Additionally, docking analysis revealed NOS3 as the gene that interacts with all the short-listed drugs, suggesting its possible involvement in the mechanisms underlying the therapeutic potential of these drugs in sporadic ALS. Overall, our study provides a systematic framework for identifying potential drug candidates for sporadic ALS therapy and highlights the potential of drug repurposing as a promising strategy for discovering new therapies for neurodegenerative diseases.

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Drug repurposing in psoriasis, performed by reversal of disease-associated gene expression profiles

Cited by 26 publications

References 39 publications

Acenocoumarol, an Anticoagulant Drug, Prevents Melanogenesis in B16F10 Melanoma Cells

Acenocoumarol, an Anticoagulant Drug, Prevents Melanogenesis in B16F10 Melanoma Cells

Revolutionizing drug development: harnessing the potential of organ-on-chip technology for disease modeling and drug discovery

Integrating Transcriptomic and Structural Insights: Revealing Drug Repurposing Opportunities for Sporadic ALS

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