A5083659157- Psoriasis: Treatment and Pathogenesis
- Cytokine Signaling Pathways and Interactions
- Dermatology and Skin Diseases
- Asthma and respiratory diseases
- Chronic Lymphocytic Leukemia Research
- Monoclonal and Polyclonal Antibodies Research
- Phytochemistry and Bioactive Compounds
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Inflammatory Bowel Disease
- Immune responses and vaccinations
- Urticaria and Related Conditions
- Autoimmune Bullous Skin Diseases
- Rheumatoid Arthritis Research and Therapies
- Lymphoma Diagnosis and Treatment
- Protein Kinase Regulation and GTPase Signaling
- HER2/EGFR in Cancer Research
- Protein purification and stability
- NF-κB Signaling Pathways
- Spondyloarthritis Studies and Treatments
- Toxin Mechanisms and Immunotoxins
- Long-Term Effects of COVID-19
- Cell Adhesion Molecules Research
- Nanofabrication and Lithography Techniques
- Immunodeficiency and Autoimmune Disorders
Pfizer (United States)
2012-2023
University of Florida
2018
Columbus Oncology and Hematology Associates
2018
Immunosciences Lab (United States)
2013
Abstract The safety, tolerability, pharmacokinetics, and pharmacodynamics of PF‐06700841 were assessed in a randomized, double‐blind, placebo‐controlled, single‐ multiple‐dose escalation, parallel‐group study healthy subjects patients with plaque psoriasis. single ascending dose (1, 3, 10, 30, 100, or 200 mg) multiple (MAD; PF‐06700841; up to 175 mg once daily 50 twice for 10 days) periods included 54 participants. In addition, 30 psoriasis received 100 placebo 28 days. Single doses rapidly...
PF‐04965842 is an oral Janus kinase 1 inhibitor being investigated for the treatment of plaque psoriasis. To evaluate efficacy, safety and tolerability in patients with moderate‐to‐severe Patients this phase II, placebo‐controlled study (NCT02201524) were randomized to receive placebo, 200 mg once daily (OD), 400 OD or twice (TD) 4 weeks. The primary endpoint was change from baseline Psoriasis Area Severity Index (PASI) at week 4. Study enrolment discontinued on 25 June 2015 due changes...
Aims To determine the safety, tolerability, pharmacokinetics and pharmacodynamics of Janus kinase 1‐selective inhibitor, PF‐04965842. Methods This was a phase 1, first‐in‐human, randomized, double‐blind, placebo‐controlled, combination single‐ multiple‐dose escalation, parallel design study in healthy subjects ( http://clinicaltrials.gov , NCT01835197). Subjects received single dose placebo or 3, 10, 30, 100, 200, 400 800 mg PF‐04965842 (single ascending phase) 30 once daily (QD), 100 QD,...
While myriad molecular formats for bispecific antibodies have been examined to date, the simplest structures are often based on scFv. Issues with stability and manufacturability in scFv-based molecules, however, a significant hindrance their development, particularly high-concentration, stable formulations that allow subcutaneous delivery. Our aim was generate tetravalent molecule targeting two inflammatory mediators synergistic immune modulation. We focused an scFv-Fc-scFv format, flexible...
Selective inhibition of tyrosine kinase 2 (TYK2) may offer therapeutic promise in inflammatory conditions, with its role downstream pro‐inflammatory cytokine signaling. In this first‐in‐human study, we evaluated the safety, tolerability, and pharmacokinetics (PK) a novel TYK2 inhibitor, PF‐06826647, healthy participants. This phase I, randomized, double‐blind, placebo‐controlled, parallel‐group study included two treatment periods (single ascending dose (SAD) multiple (MAD)) participants...
To aid in the pursuit of selective kinase inhibitors, we have developed a unique ATP site binder tool for detection binders outside by nuclear magnetic resonance (NMR). We report here novel synthesis that led to this paramagnetic spin-labeled pyrazolopyrimidine probe (1), which exhibits nanomolar inhibitory activity against multiple kinases. demonstrate application performing NMR binding experiments with Lck and Src kinases utilize it detect two compounds proximal site. The complex structure...
Protein biosynthesis and extracellular secretion are essential biological processes for therapeutic protein production in mammalian cells, which offer the capacity correct folding proper post-translational modifications. In this study, we have generated bispecific fusion proteins cells by combining a peptide an antibody into single open reading frame. A neutralizing directed against interleukin-17A (IL17A) was genetically fused to N termini of anti-IL22 antibody, through either light chain,...
Transcription factor retinoic acid-related orphan receptor 2 (RORC2/RORγT) mediates interleukin (IL)-17A and IL-17F expression. IL-17A plays a central role in the pathogenesis of several inflammatory disorders, including psoriasis. The RORC2 inhibitor PF-06763809 has been hypothesized to inhibit production T-helper 17 (Th17) cells, thereby reducing psoriasis symptoms.To assess safety, tolerability effect on skin infiltrate thickness participants with mild/moderate chronic plaque...
Challenges in using cytokine data are limiting Coronavirus Disease 2019 (COVID-19) patient management and comparison among different disease contexts. We suggest mitigation strategies to improve the accuracy of data, as we learn from experience gained during COVID-19 pandemic.
Ritlecitinib is a small molecule in clinical development that covalently and irreversibly inhibits Janus kinase 3 (JAK3) the TEC family of kinases (BTK, BMX, ITK, TXK, TEC). This phase 1, open-label, parallel-group study assessed target occupancy functional effects ritlecitinib on JAK3 healthy participants aged 18-60 years who received 50 or 200 mg single doses day 1. Blood samples to assess pharmacokinetics, occupancy, pharmacodynamics were collected over 48 hours. Target was using mass...
Disease caused by novel coronavirus SARS-CoV-2 (COVID-19) has resulted in significant morbidity and mortality worldwide. One mechanism of severe disease is thought to be a cytokine storm subset patients, where hyper-inflammatory state characterized elevated levels circulating cytokines chemokines portend poor prognosis. We report on our experience clinical laboratory assessment patients hospitalized with COVID-19. demonstrate alarming discrepancies reported different vendors. Our findings...