Ace Therapeutics empowers pharmaceutical companies and researchers in their pursuit of novel therapies for inflammatory bowel disease (IBD) by providing comprehensive Janus kinase (JAK) inhibitor development services. Our expertise in medicinal chemistry, disease modeling, and drug efficacy evaluation assists our customers in selecting and optimizing the most promising compounds for further development.
The Role of JAKs in IBD
JAKs are a family of intracellular tyrosine kinases that play a critical role in signal transduction pathways activated by cytokines. In IBD, JAKs mediate the signaling of pro-inflammatory cytokines such as TNF-α, IL-6, and IFN-γ, which promote the activation and differentiation of immune cells, leading to tissue damage and inflammation in the gut. This makes JAKs a promising target for IBD therapy. Inhibition of JAKs can effectively dampen the inflammatory cascade, reduce the production of pro-inflammatory cytokines and attenuate the severity of IBD symptoms.
Figure 1. JAK-associated receptors play a pleiotropic role in inflammatory bowel disease. (Salas A., et al., 2020)
What Can We Do for the Development of JAK Inhibitors?
- Target Validation and Profiling
We offer target validation services to elucidate the specific roles of JAK isoforms in the pathogenesis of IBD and to select appropriate drug targets. Our services include the identification of the key JAKs involved in inflammatory pathways, their downstream signaling cascades, and their contribution to disease progression using advanced techniques such as RNA sequencing, proteomics, and functional assays.
- Evaluation of the Efficacy of JAK Inhibitors
In Vitro Studies
In Vivo Studies
We utilize a variety of established cell lines relevant to IBD, such as T cells, macrophages, and intestinal epithelial cells to help you assess the potency and selectivity of JAK inhibitors in blocking inflammatory signaling pathways.
- Functional Assays: Measure the ability of JAK inhibitors to block JAK-mediated phosphorylation of downstream signaling molecules, ultimately inhibiting the production of pro-inflammatory cytokines.
- Binding Assays: Determine the affinity and selectivity of inhibitors for specific JAK isoforms using techniques such as radioligand binding assays and surface plasmon resonance.
We conduct preclinical studies in animal models of IBD, such as dextran sulfate sodium (DSS)-induced colitis mice or TNBS-induced colitis rats. These models allow us to evaluate the efficacy of JAK inhibitors in reducing disease severity.
- Measurements: Weight loss, stool consistency, and colon length.
- Histological analysis: Assess inflammation, ulceration, and tissue damage in the colon.
- Cytokine profiling: Measure levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in the colon and serum.
- Safety Evaluation of JAK Inhibitors
Our expertise in preclinical safety assessment allows us to conduct a comprehensive evaluation that includes studies to assess potential off-target effects, toxicity profiles, and long-term safety. We utilize a variety of in vitro and in vivo models to evaluate the safety of your JAK inhibitor candidate by studying cardiovascular function, hematological parameters, and organ function.
- Combination Therapy Screening & Assays
At Ace Therapeutics, we understand that combining JAK inhibitors with other well-established IBD therapies can offer synergistic benefits and potentially enhance treatment outcomes. Our expertise in drug combination studies allows us to investigate the potential for combining JAK inhibitors with biologics, corticosteroids, or other immunomodulators. We conduct both in vitro and in vivo studies to assess the efficacy and safety of these combination therapies, exploring optimal dosing regimens and routes of administration to maximize efficacy and minimize adverse effects.
Ace Therapeutics is your partner in the development of novel JAK inhibitors for the treatment of inflammatory bowel disease. Our experts are dedicated to supporting you through every stage of preclinical research and evaluation. Contact us today to discuss your specific needs.
References
- Salas A., et al. JAK-STAT pathway targeting for the treatment of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2020, 17(6):323-337.
- Honap S.; et al. JAK inhibitors for inflammatory bowel disease: recent advances. Frontline Gastroenterol. 2023, 15(1):59-69.
Related Services
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