Article Figures & Data
Figures
- Fig. 1.
Transport of glucose-conjugated antipsoriatic drugs through GLUT1 in keratinocytes. In contradistinction to healthy keratinocytes (A), hyperproliferative keratinocytes are composed of overexpressed GLUT1 transporters, which contribute to significantly higher uptake of glucose-conjugated drugs (B). As a result, in chronic inflammation, the glucose-conjugated antipsoriatic drugs may lead to reduced inflammation and hyperproliferation of keratinocytes. The intracellular cleavage of acid-labile linkers in the more acidic environment results in controlled drug release in hyperproliferative keratinocytes.
- Fig. 2.
Synthesis of glucose-conjugated antipsoriatic drugs. Synthesis of (A) acitretin glycoconjugate, (B) tofacitinib glycoconjugate, and (C) cyclosporin glycoconjugate.
Tables
- TABLE 1
FDA-approved traditional and biologic therapies for psoriasis
Agents have been classified into two main groups: 1) systemic immunosuppressives used for the treatment of moderate to severe psoriasis; and 2) biologic agents divided into TNF-α inhibitors, IL-17 inhibitors, and IL-23 and related cytokine inhibitors.
Class Compound Mechanism of action Traditional agents commonly used in treatment of moderate to severe psoriasis Methotrexate A folate antimetabolite that inhibits T-cell activation as well as DNA synthesis and repair (Chan and Cronstein, 2013) Cyclosporine A calcineurin inhibitor that leads to reduced production of interleukin-2 (Matsuda and Koyasu, 2000) Apremilast A phosphodiesterase 4 inhibitor that leads to increased intracellular cAMP levels to regulate various inflammatory mediators (e.g., decreases levels of TNF-α and interleukin-23, increases level of interleukin-10) (Schafer, 2012) Tofacitinib An inhibitor of interleukin-2-induced phosphorylation of JAK3 and STAT5, which are involved in immune cell function (Hodge et al., 2016) Fumaric acid esters Fumarate derivatives that activate Nrf2 to inhibit the production of proinflammatory cytokines, such as IL-12 and IL-23 (Balak, 2015) Acitretin A retinoid that binds to and activates retinoid receptors to normalize keratinocyte differentiation in the epidermis (Tippmann et al.,2009) Biologic agents TNF-α inhibitors Etanercept A recombinant protein that binds to the Fc portion of IgG and blocks soluble TNF-α interaction with receptors on the cell surface (Goffe and Cather, 2003) Infliximab A chimeric monoclonal antibody that interferes with endogenous TNF-α (Guo et al., 2013) Adalimumab A recombinant monoclonal antibody against TNF-α (Mease, 2007) Certolizumab pegol A pegylated Fab’ fragment of humanized monoclonal antibody against TNF-α; selectively binds and neutralizes the activity of human TNF-α (Acosta-Felquer et al., 2016) Interleukin 17 inhibitors Secukinumab A human IgG1κ monoclonal antibody that selectively binds to interleukin-17A and inhibits the interaction of this cytokine with the IL-17 receptor (Fala, 2016) Ixekizumab A humanized IgG4κ monoclonal antibody against IL-17A, that inhibits the release of proinflammatory cytokines and chemokines (Monin and Gaffen, 2018) Brodalumab A human monoclonal IgG2 antibody that acts as an antagonist of IL-17 receptor A (IL-17RA) to block the release of proinflammatory cytokines and chemokines (Monin and Gaffen, 2018) Interleukin 23 and related cytokines inhibitors Ustekinumab A human IgGκ monoclonal antibody that binds with high affinity to p40 subunit of both IL-12 and IL-23 to reduce the expression of key cytokines, such as MCP-1, TNF-α, IP-10, and IL-8 (Benson et al., 2011) Guselkumab A human IgG1λ monoclonal antibody that selectively blocks the IL-23 receptor and reduces the serum levels of IL-17A, IL-17F, and IL-22 (Al-Salama and Scott, 2018) Tildrakizumab A human IgG1κ monoclonal that binds to the p19 subunit of IL-23 and consequently inhibits its interaction with the IL-23 receptor (Papp et al., 2015) Risankizumab A human IgG1 monoclonal antibody against the p19 subunit of IL-23, resulting in inhibition of its interaction with the IL-23 receptor (Haugh et al., 2018) FDA, Food and Drug Administration. STAT5, Signal transducer and activator of transcription 5. Nrf2, Nuclear factor erythroid 2-related factor 2. MCP-1, Monocyte chemoattractant protein-1.
