N-hetaryformamidine-based dual IL-17 and IL-23 inhibitors for psoriasis and inflammatory skin disease treatment
Novel small molecule N-hetaryformamidine (HF) compounds that inhibit both IL-17 and IL-23 cytokine pathways for treating psoriasis and related inflammatory conditions. Initial screening shows potent IL-17 inhibition with IC50 values of 0.34–0.63 µM and low cytotoxicity, comparable to leading reference compounds.
Overview
This research presents a novel class of small molecule inhibitors based on the N-hetaryformamidine (HF) scaffold, designed to simultaneously target IL-17 and IL-23 cytokine pathways. These dual inhibitors offer a promising new approach for managing inflammatory skin diseases such as psoriasis, with potential extension to asthma depending on the route of administration. The compounds are synthesized through a multicomponent reaction producing N-pyrazolylformamidines, providing an efficient and scalable route to novel therapeutic candidates. By addressing both IL-17 and IL-23, these inhibitors target two key drivers of chronic inflammation, potentially offering improved efficacy over single-pathway interventions.
Technical specifications
Key features and capabilities:
- Compounds synthesized via multicomponent reaction producing N-pyrazolylformamidines
- Dual targeting of IL-17 and IL-23 cytokine secretion pathways
- IL-17 inhibitory activity with IC50 values ranging from 0.34 to 0.63 µM in stimulated human peripheral blood mononuclear cells (hPBMC)
- Favorable cytotoxicity profile with EC50 values greater than 30 µM against hPBMC
- Activity comparable to potent reference compounds including TAK-828F, GNE-6468, and CDDO-Im
- Selectivity in inhibiting IL-17 secretion while sparing cell viability
- Preliminary structure-activity relationship (SAR) data enabling rational design of next-generation molecules
Validation methodology:
- In vitro screening using memory T-cells stimulated by anti-CD3, anti-CD28, and IL-23 in hPBMC
- IL-17 secretion quantified via ELISA assays
- Cytotoxicity assessed against hPBMC to establish selectivity windows
Technology readiness level
The technology is currently at an early-to-mid stage of preclinical development. Hit compounds have been identified through in vitro screening with demonstrated potent IL-17 inhibition and acceptable safety margins in cell-based assays. Preliminary structure-activity relationship data have been established, enabling informed design of optimized derivatives. Future validation efforts are planned to further characterize efficacy, optimize pharmacokinetic properties, and advance toward in vivo studies. The scaffold shows strong potential for expansion into dual IL-17/IL-23 inhibitors suitable for inflammatory skin disease therapeutics.
About Lipidware Sdn Bhd
Lipidware Sdn Bhd is a Malaysian biotechnology company founded in 2017 as a university startup from Universiti Putra Malaysia (UPM) through the Putra Science Park InnoHub Programme. The company specializes in translating academic research into commercialized skincare solutions, most notably its REMDII brand. Developed by researchers in biotechnology and biochemistry, the company’s core innovation involves a patented bioactive delivery system that utilizes full-spectrum tocotrienols—a form of Vitamin E—to provide targeted anti-inflammatory and barrier-repair properties for sensitive and eczema-prone skin. This research-driven approach includes rigorous independent testing and ethics-approved human clinical trials to ensure safety and efficacy as a steroid-free alternative for individuals of all ages.
Beyond product development, Lipidware plays a significant role in community education and support through the Malaysia Eczema Support Community (MESC), which provides resources and guidance for patients and caregivers. The company’s efforts bridge the gap between clinical science and practical health management, addressing skin conditions such as atopic dermatitis, psoriasis, and actinic keratosis. Through its commitment to real science, Lipidware has earned numerous national and international accolades for innovation and commercialization, successfully moving university-backed breakthroughs from the laboratory to pharmacy shelves to improve patient quality of life.
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