Psoriasis

Calcipotriol is a synthetic VitD₃ analogue with a high affinity for the vitamin D receptor.

Methotrexate (Amethopterin; CL14377; WR19039) is an orally active antifolate (Antifolate). Methotrexate inhibits dihydrofolate reductase (DHFR), blocks tetrahydrofolate production, suppresses purine/pyrimidine synthesis and transmethylation, and causes intracellular accumulation of AICAR. Methotrexate promotes extracellular adenosine release, regulates the cytokine network, and inhibits the alarmin function of HMGB1. Methotrexate induces apoptosis and cytotoxicity, upregulates the expression of iNOS and COX-2, suppresses hippocampal neurogenesis, and induces pulmonary fibrosis. Methotrexate is used in the research of various immune and inflammation-related diseases such as arthritis, psoriasis, systemic lupus erythematosus, as well as pulmonary fibrosis and breast cancer.

Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist used clinically to treat type 2 diabetes mellitus.

Deucravacitinib (BMS-986165) is an orally active allosteric inhibitor of tyrosine kinase 2 (TYK2), with an IC₅₀ of 0.2 nM and a K_i of 0.02 nM against the JH2 domain of TYK2, and it exhibits selectivity over other JAK subtypes and most of the kinome. Deucravacitinib blocks IL-23, IL-12, p-STAT1/3 and Type I IFN signaling, and inhibits Th17/Th1-mediated psoriasis inflammation. Deucravacitinib can be used in research related to moderate-to-severe plaque psoriasis, inflammatory bowel disease and systemic lupus erythematosus.

Doramapimod (BIRB 796) is an orally active, highly potent p38 MAPK inhibitor, which has an IC₅₀ for p38α=38 nM, for p38β=65 nM, for p38γ=200 nM, and for p38δ=520 nM. Doramapimod has picomolar affinity for p38 kinase (K_d=0.1 nM). Doramapimod also inhibits B-Raf with an IC₅₀ of 83 nM.

Propranolol is a nonselective and BBB-permeable β-adrenergic receptor (βAR) antagonist, has high affinity for the β1AR and β2AR with K_i values of 1.8 nM and 0.8 nM, respectively. Propranolol inhibits [³H]-DHA binding to rat brain membrane preparation with an IC₅₀ of 12 nM. Propranolol is used for the study of hypertension, pheochromocytoma, myocardial infarction, cardiac arrhythmias, angina pectoris, and hypertrophic cardiomyopathy.

Enpatoran (M5049) is an orally active and selective TLR7/8 antagonist. Enpatoran inhibits the activation of the downstream type I interferon pathway. Enpatoran is used in studies of cutaneous lupus erythematosus, systemic lupus erythematosus with cutaneous manifestations, and psoriasis.

Methotrexate disodium (Amethopterin disodium; CL14377 disodium; WR19039 disodium) is an orally active antifolate (Antifolate). Methotrexate disodium inhibits dihydrofolate reductase (DHFR), blocks tetrahydrofolate production, suppresses purine/pyrimidine synthesis and transmethylation, and causes intracellular accumulation of AICAR. Methotrexate disodium promotes extracellular adenosine release, regulates the cytokine network, and inhibits the alarmin function of HMGB1. Methotrexate disodium induces apoptosis and cytotoxicity, upregulates the expression of iNOS and COX-2, suppresses hippocampal neurogenesis, and induces pulmonary fibrosis. Methotrexate disodium is used in the research of various immune and inflammation-related diseases such as arthritis, psoriasis, systemic lupus erythematosus, as well as pulmonary fibrosis and breast cancer.

SGC-CBP30, a chemical probe, is a potent and highly selective CBP/p300 bromodomain (K_ds of 21 nM and 32 nM for CBP and p300, respectively) inhibitor, displaying 40-fold selectivity over the first bromodomain of BRD4 [BRD4(1)] bound. SGC-CBP30 strongly reduces secretion of IL-17A in Th17 cells and has anti-inflammatory effects.

Icotrokinra (JNJ-77242113) is an orally available, selective antagonist of the IL-23 receptor. Icotrokinra inhibits IL-23-induced STAT3 phosphorylation in peripheral blood mononuclear cells (IC₅₀=5.6 pM) and inhibits IL-23-induced interferon IFN-γ production in NK cells with an IC₅₀ of 18.4 pM. Icotrokinra exhibits anti-inflammatory activity in a rat TNBS-induced colitis model. Icotrokinra can be used in the study of psoriasis, psoriatic arthritis, and inflammatory bowel disease.

Bimekizumab (Anti-Human IL17A/IL-17F Recombinant Antibody) is a humanised monoclonal antibody, can selectively neutralises IL-17A and IL-17F. Both of them are pro-osteogenic with respect to human periosteum-derived cell (hPDC) differentiation. Thus Bimekizumab blocks the inflammation-driven osteogenic differentiation.

Ustekinumab is an anti-IL-12/IL-23 IgG1κ human monoclonal antibody.

Secukinumab (AIN457) is a high affinity, human monoclonal antibody targeted against interleukin (IL)-17A. Secukinumab is the first-in-class anti-IL-17 agent used for the research of plaque psoriasis, ankylosing spondylitis and psoriatic arthritis.

Urea is a powerful protein denaturant via both direct and indirect mechanisms. A potent emollient and keratolytic agent. Used as a diuretic agent. Blood urea nitrogen (BUN) has been utilized to evaluate renal function. Widely used in fertilizers as a source of nitrogen and is an important raw material for the chemical industry.

Risankizumab (BI 655066) is a humanised IgG monoclonal antibody, targeting IL-23 p19 subunit (K_d <10 pM) and inhibiting IL-17 production induced by human IL-23 in mouse splenocytes (IC₅₀ = 2 pM). Risankizumab can be used to research immunological and inflammatory disorders such as psoriasis vulgaris, psoriatic arthritis, generalized pustular psoriasis and erythrodermic psoriasis.

PMX-53 (3D53) is a synthetic peptidic and a potent and orally active complement C5a receptor (CD88) antagonist with an IC₅₀ of 20 nM. PMX-53 is also a low-affinity MrgX2 agonist that stimulates MrgX2-mediated mast cell degranulation. PMX-53 specifically binds to C5aR1 and does not bind to the second C5aR (C5L2) and C3aR. PMX-53 has anti-inflammatory, anticancer and antiatherosclerotic effects.

Guselkumab is a recombinant human IgG1 monoclonal antibody against the IL-23p19 subunit. Guselkumab binds to human and cynomolgus monkey IL-23 with K_d values of 3.3 and 1.9 pmol/L, respectively. Guselkumab inhibits production of cytokines lying downstream of the IL-23 signaling pathway and can be used for psoriatic arthritis research.

Soquelitinib (CPI-818) is an orally active and highly selective covalent interleukin-2-inducible kinase (ITK) inhibitor. Soquelitinib is active in six different models of T cell-mediated inflammatory and immune disease, including acute and chronic asthma, pulmonary fibrosis, systemic sclerosis (scleroderma), psoriasis, and acute graft versus host disease with Th2 cytokine product inhibition. Soquelitinib increases tumor infiltration of normal CD8⁺ cells that possess enhanced T effector function.

Methoxsalen (8-Methoxypsoralen) is a furanocoumarin compound used in psoralen, used in studies of psoriasis, eczema, vitiligo and some sun-exposed cutaneous lymphomas, and is a P450 inhibitor.

Triclosan is a broad-spectrum antibacterial agent that inhibits bacterial fatty acid synthesis at the enoyl-acyl carrier protein reductase (FabI) step. Triclosan inhibits E. coli enoyl-acyl carrier protein reductase (FabI) and FabI containing a glycine-to-valine substitution at position 93 (FabIG93V) with IC₅₀s of 2 µM and 10 µM, respectively. Triclosan causes apoptotic effect in cultured rat neural stem cells (NSC). Triclosan exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models.