Psoriasis and autoimmune arthritis represent distinct yet mechanistically interconnected inflammatory diseases driven by chronic immune dysregulation [1]. Despite their dissimilar clinical manifestations, these conditions are closely linked: up to 30 % of patients with psoriasis develop psoriatic arthritis as their disease progresses [4]. This strong clinical association reflects shared immunopathogenic mechanisms, including dysregulated cytokine signaling, innate immune activation and genetic predisposition. Targeting these common pathways offers opportunities for therapies that can address both skin and joint inflammation.
To advance drug discovery in autoimmune inflammatory disorders, Life Chemicals has developed a dedicated collection of over 7,800 drug-like screening compounds optimized for high-throughput screening (HTS) against shared inflammatory and immune signaling pathways implicated in psoriasis, psoriatic arthritis (PsA), rheumatoid arthritis (RA) and related conditions.
The Library was constructed using two complementary design strategies:
- Autoimmune Inflammatory Targeted Screening Set (1,200 compounds)
Built using structure-based virtual docking, this subset includes compounds predicted to modulate early disease drivers and key immune mediators within core inflammatory signaling pathways - Autoimmune Inflammatory Focused Screening Set (6,600 compounds)
Developed through ligand-based virtual screening, this set comprises compounds that are highly structurally similar to known modulators of emerging and clinically relevant targets. It contains a dermal-optimized subset featuring 1,400 compounds with physicochemical properties favorable for efficient skin penetration
Together, these subsets provide a strategically designed starting point for identifying novel modulators of immune-driven inflammation
The compound selection can be customized based on your requirements. Cherry-picking is available.
Please, contact us at orders@lifechemicals.com for any additional information and price quotations.
Representative screening compounds from the Arthritis and Psoriasis Screening Library
Scientific rationale
Psoriasis and inflammatory arthritis, including psoriatic arthritis (PsA) and rheumatoid arthritis (RA), are chronic immune-mediated inflammatory diseases that significantly impair patient quality of life. Psoriasis primarily affects the skin, typically presenting itself as erythematous, scaly skin lesions. Inflammatory arthritis is characterized by joint inflammation, pain, and progressive disability. It encompasses a heterogeneous group of joint disorders, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), osteoarthritis (OA), reactive arthritis, crystal-induced arthritis (e.g., gout), and virus-associated arthritis [2,3].
A wide spectrum of therapeutic targets has been described across these disease types (Figures 1, 2). Key drivers include pro-inflammatory cytokines (TNF-α, IL-6, IL-17, IL-23), innate immune receptors (TLR1/2/7), the NLRP3 inflammasome, and intracellular signaling cascades, such as NF-κB, MAPK, PI3K/AKT, JAK/STAT, and SYK [5–7].
Osteoarthritis (OA) progression involves IL-1β, TNF-α, IL-6, matrix metalloproteinases (MMP-1, MMP-3, MMP-13), and signaling via NF-κB, MAPK, PI3K-AKT, SYK, Notch, cGAS-STING, and IRF3-IKK pathways. Rheumatoid arthritis (RA) is driven by persistent synovial inflammation mediated by TNF-α, IL-6, IL-1β and downstream kinases, including JAKs and SYK [8,9].
Psoriatic arthritis (PsA) shares many inflammatory mechanisms but is uniquely influenced by IL-17, IL-22, IL-23/IL-23R signaling, and genetic associations, such as HLA-B27 and ERAP2. Virus-associated arthritis, including that linked to Parvovirus B19, Chikungunya virus and SARS-CoV-2, involves acute immune activation through TNF-α, IL-6, TLRs and the NLRP3 inflammasome [10].
In parallel, psoriasis is characterized by immune-driven keratinocyte hyperproliferation mediated by type I and II interferons (IFN-α, IFN-γ), TNF-α, IL-12, IL-17, IL-22, IL-23, and IL-36. Intracellular mediators, such as TYK2, JAKs, STAT1/3, and ROCK2, play key roles in sustaining chronic inflammation. Additional targets, including IL-21, PDIA3 and cytochrome P450 enzymes, such as CYP1A1, further expand therapeutic opportunities [11,12].
Compound selection
An in-depth literature review and a target-focused analysis of disease-relevant signaling pathways drove our compound selection.
Autoimmune Inflammatory Targeted Screening Set (1,200 compounds)
Generated through structure-based virtual docking against our proprietary HTS Compound Collection, this set was derived from our broader Anti-inflammatory Screening Compound Library. It focuses on compounds relevant to psoriatic and rheumatoid inflammation, prioritizing modulators of early disease drivers and key immune mediators.
Associated biological targets are specified per compound in the SDF file for easy filtering and analysis.
Autoimmune Inflammatory Focused Screening Set (6,600 compounds)
Ligand-based virtual screening using 2D molecular fingerprints identified compounds with high structural similarity (Tanimoto ≥ 0.85) to known modulators of disease-associated targets. Reference molecules, narrowed to compounds with experimentally confirmed bioactivity, were extracted from the ChEMBL. This approach enriched the set with novel scaffolds and chemotypes while maintaining broad chemical diversity suitable for HTS and downstream optimization.
The SDF file allows filtering by target, disease and organism, subset and key physicochemical properties to support flexible data handling.
Dermal-optimized Subset for Topical Drug Discovery (1,400 compounds)
To support topical and localized therapeutic development, a dermal-optimized subset was created based on physicochemical properties predictive of favorable skin penetration and minimal systemic exposure:
- Molecular Weight (MW): 200–400 Da
- Clog P: 1-3
- Topological Polar Surface Area (TPSA): < 140 Ų
- H-Bond Donors (HBD): ≤ 5
- H-Bond Acceptors (HBA): ≤ 8
- Rotatable Bonds: ≤ 8
These criteria correspond to an estimated percutaneous permeability coefficient (Kₚ ≈ –4 on a log scale), enabling efficient localized absorption while minimizing systemic distribution.
The Dermal-optimized subset is derived from the broader Autoimmune Inflammatory Focused Screening Set, providing a targeted option for topical and localized therapeutic screening. Compounds can be filtered by subset directly in the supplied SDF.
![Pathological processes in psoriatic disease (PsD) (figure adapted from [13])](img/library_descriptions/Autoimmune%20Inflammatory%20Arthritis%20and%20Psoriasis%20Screening%20Libraries/Autoimmune%20Inflammatory_1.png "Pathological processes in psoriatic disease (PsD) (figure adapted from [13])")
Figure 1. Pathological processes in psoriatic disease (PsD) (figure adapted from [13]).
![Targeted therapies. Mechanism of action of the latest approved or in-development molecules for the treatment of PsA. Interleukin 17 (IL-17) and isoforms IL-17A/F/E and IL17 receptor (IL-17R); janus kinase 1, 2, 3 (JAK1, JAK2, JAK3) and tyrosine kinase 2 (TYK2) (figure adapted from [13]).](img/library_descriptions/Autoimmune%20Inflammatory%20Arthritis%20and%20Psoriasis%20Screening%20Libraries/Autoimmune%20Inflammatory_2.png "Targeted therapies. Mechanism of action of the latest approved or in-development molecules for the treatment of PsA. Interleukin 17 (IL-17) and isoforms IL-17A/F/E and IL17 receptor (IL-17R); janus kinase 1, 2, 3 (JAK1, JAK2, JAK3) and tyrosine kinase 2 (TYK2) (figure adapted from [13]).")
Figure 2. Targeted therapies. Mechanism of action of the latest approved or in-development molecules for the treatment of PsA. Interleukin 17 (IL-17) and isoforms IL-17A/F/E and IL17 receptor (IL-17R); janus kinase 1, 2, 3 (JAK1, JAK2, JAK3) and tyrosine kinase 2 (TYK2) (figure adapted from [13]).
Reference:
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11. Popa OM, Cherciu M, Cherciu LI, Dutescu MI, Bojinca M, Bojinca V, Bara C, Popa LO. ERAP1 and ERAP2 Gene Variations Influence the Risk of Psoriatic Arthritis in the Romanian Population. Arch Immunol Ther Exp (Warsz). 2016 Dec;64(Suppl 1):123-129. doi: 10.1007/s00005-016-0444-4.
12. Zhang Y, Yang W, Li W, Zhao Y. NLRP3 Inflammasome: Checkpoint Connecting Innate and Adaptive Immunity in Autoimmune Diseases. Front Immunol. 2021;12:732933. Published 2021 Oct 11. doi:10.3389/fimmu.2021.732933
13. Azuaga, A.B.; Ramírez, J.; Cañete, J.D. Psoriatic Arthritis: Pathogenesis and Targeted Therapies. Int. J. Mol. Sci. 2023, 24, 4901. https://doi.org/10.3390/ijms24054901