Small molecules under development for psoriasis: on the road to the individualized therapies

Cervantes-Durán, Claudia; María-Elena, Velázquez-Hernández; Josué, Valentín-Escalera; Bartolomé-Camacho, María-Carmen; Alain-Raimundo, Rodríguez-Orozco; García-Pérez, Martha-Estrella

doi:10.1007/s00403-020-02056-3

Cited by 17 publications

(9 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Even in the same patient, psoriasis characteristics can vary widely. 10 Therefore, it may be difficult to meet the needs of patients with a single drug for the treatment of psoriasis and its complications. In this study, we selected psoriasis patients with the same characteristics while searching for biomarkers and therapeutic targets by monitoring their metabolite changes (which can provide real-time feedback on changes in the patient's phenotype).…”

Section: Discussionmentioning

confidence: 99%

“…Undoubtedly, the understanding of the immunologic, genetic, and molecular aspects of psoriasis has contributed significantly to the identification of novel drugs, new targets, and holistic approaches in recent decades, leading to the development of increasingly personalized therapeutic targets such as cytokines (tumor necrosis factor [TNF], interleukins [IL] 12/23, 17, and 23) and personalized treatment drugs such as biologics, JAK /TYK inhibitors, and phosphodiesterase-4 (PDE-4) inhibitors. [10][11][12] However, their clinical manifestations still need to be defined and evaluated, so there is still a long way to go before achieving the dream goal of personalized treatment for this disease. 11,12 Therefore, it is also imperative to continue to search for new targets that target the characteristics of various psoriasis subtypes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Metabolomics Reveals Molecular Signatures for Psoriasis Biomarkers and Drug Targets Discovery

Song,

Chen,

et al. 2023

CCID

View full text Add to dashboard Cite

Psoriasis is a chronic, multi-system skin disease that can be influenced by immunological, environmental, and genetic factors. Plasma metabolomic analysis can provide a great deal of information on potential diagnostic biomarkers, pathogenesis and personalized treatment. However, the role of metabolites in psoriasis is unknown. Patients and Methods: We performed an untargeted metabolomic analysis of plasma based on high-resolution liquid chromatography mass spectrometry from 10 plaque psoriasis patients and 10 healthy controls. Results: A total of 301 differential metabolites were detected, of which 10 metabolites were possible potential biomarkers, including vitamins, amino acids, and lipids. At the same time, KEGG pathway enrichment analysis was performed for all detected differential metabolites, and it was found that protein digestion and absorption, amino acid metabolism and lipid metabolism may be jointly involved in regulating the pathogenesis of psoriasis. In addition, the proteins ESR1, OPRM1 and HSD11B1 were identified as possible potential topical therapeutic targets for psoriasis through analysis of the metabolite-protein interaction network. Conclusion:In this study, we identified 10 differential metabolites as possible potential combinatorial biomarkers for the diagnosis of psoriasis. 12 metabolic pathways were significantly enriched that may be closely related to the occurrence and development of psoriasis. Three proteins, ESR1, OPRM1, and HSD11B1, were identified as possible potential therapeutic targets for psoriasis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metabolomics Reveals Molecular Signatures for Psoriasis Biomarkers and Drug Targets Discovery

Song,

Chen,

et al. 2023

CCID

View full text Add to dashboard Cite

show abstract

“…Small molecules are small-molecular-weight inhibitors (<1 kDa) that can enter the cells and selectively inhibit signaling pathways [193]. Some advantages they offer to traditional therapies are the topical or oral route of administration, lack of immunogenicity, and low costs of production [194].…”

Section: Small Molecule Therapiesmentioning

confidence: 99%

Inflammation and Psoriasis: A Comprehensive Review

Man,

Orăsan,

Hoteiuc

et al. 2023

IJMS

View full text Add to dashboard Cite

Psoriasis is an immune-mediated disease with a strong genetic component that brings many challenges to sick individuals, such as chronic illness, and which has multiple associated comorbidities like cardiovascular disease, metabolic syndrome, inflammatory bowel disease, and psychological disorders. Understanding the interplay between the innate and adaptative immune system has led to the discovery of specific cytokine circuits (Tumor Necrosis Factor-alpha (TNF-α), IL-23, IL-17), which has allowed scientists to discover new biomarkers that can be used as predictors of treatment response and pave the way for personalized treatments. In this review, we describe the footprint psoriasis leaves on the skin and beyond, key pathophysiological mechanisms, current available therapeutic options, and drawbacks faced by existing therapies, and we anticipate potential future perspectives that may improve the quality of life of affected individuals.

show abstract

“…La PDE4 es una enzima intracelular responsable de la hidrólisis de monofosfato de adenosina cíclico (cAMP), un segundo mensajero que juega un papel fundamental en la regulación de la respuesta inmune (19). La actividad reducida de PDE4 aumenta el nivel de cAMP citosólico, disminuyendo los mediadores proinflamatorios y elevando la producción de factores antiinflamatorios.…”

Section: Inhibidores De La Fosfodiesterasa 4 (Pde4)unclassified

Oral small molecules: new therapeutic targets in psoriasis

Martos-Cabrera,

Sampedro-Ruiz,

Llamas-Velasco

et al. 2023

an. ranm

View full text Add to dashboard Cite

Psoriasis is a chronic immune-mediated skin disease frequently associated with different comorbidities, among which psoriatic arthritis stands out, with a high impact on the quality of life of patients. We have an important therapeutic arsenal that includes topical agents, phototherapy and systemic drugs. In recent years, biological therapy has brought about a true revolution in the treatment of moderate to severe psoriasis, due to its great efficacy and safety. However, it has some limitations such as its exclusively parenteral administration, its high cost and the lack of efficacy and tolerance in some cases. Therefore, based on a better knowledge of the pathophysiology of psoriasis, new therapeutic options have emerged: the small molecules. They represent an enrichment for the clinician in the therapeutic management of psoriasis. Some of those have approved indication and others under investigation. The objective of this review is to analyze the efficacy and safety data of these molecules that include phosphodiesterase inhibitors (apremilast), Janus kinase inhibitors (tofacitinib, baricitinib), selective tyrosine kinase 2 inhibitors (deucravacitinib), agonists G protein-associated A3 adenosine receptor (piclidenoson), orphan T-gamma receptor inverse agonists (vimirogant), and sphingosine-1-phosphate receptor antagonists (ponesimod). In addition, new molecular targets are discussed. In short, the frontline of new systemic treatment for psoriasis.

show abstract

Small molecules under development for psoriasis: on the road to the individualized therapies

Cited by 17 publications

References 99 publications

Metabolomics Reveals Molecular Signatures for Psoriasis Biomarkers and Drug Targets Discovery

Metabolomics Reveals Molecular Signatures for Psoriasis Biomarkers and Drug Targets Discovery

Inflammation and Psoriasis: A Comprehensive Review

Oral small molecules: new therapeutic targets in psoriasis

Contact Info

Product

Resources

About