- Guide to PHARMACOLOGY
Synonyms: compound 11 [PMID: 28139931] | example 5 [WO2015083028] | Litfulo® | PF-06651600 | PF06651600
ritlecitinib is an approved drug (FDA (2023))
Compound class: Synthetic organic
Comment: Ritlecitinib (PF-06651600) is a potent, orally active, molecule with dual inhibitor activities. It acts as a covalent and selective inhibitor of Janus kinase 3 (JAK3)  (a type I inhibitor, that binds to the kinase in its ATP pocket), and it also inhibits TEC family kinases (BTK, ITK, TEC, Etk, TXK) that are involved in immune cell regulation. It has demonstrated anti-inflammatory activities in in vivo models . Ritlecitinib is example 5 in a Pfizer patent that provides SAR for 343 analogues . There are three crystal structures available for compounds reported in  with JAK3, but not for compound 11 (the PDB identifiers are 5TTV, 5TTU and 5TTS).
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
|PF-06651600 is a JAK3 inhibitor with potential clinical utility as a therapeutic option for autoimmune diseases.
Inhibition of JAK3 modulates γ-common chain cytokine pathways (e.g., IL-7, IL-9, IL-15, and IL-21) that are drivers of ulcerative colitis pathophysiology. However, unlike JAK1 inhibitors, JAK3 inhibition does not disrupt the actions of immunoregulatory cytokines (e.g., IL-10, IL-27, and IL-21) which are critical regulators of immune homeostasis in the digestive tract. Ritlecitinib-mediated inhibition of TEC family kinases impedes the functions of cytotoxic immune cells (CD8+ T cell, natural killer cells) that are involved in the pathogenesis of inflammatory bowel disease.
|Phase 2 clinical candidate for UC (NCT02958865).|
|Phase 2 clinical candidate for patients with moderate to severe CD (NCT03395184).|
||Phase 2b/3 clinical candidate for AA (NCT03732807). In August 2021, Pfizer announced that ritlecitinib had met its primary endpoint (reduction in hair loss) in this study. Results from phase 2a NCT02974868 comparing ritlecitinib and brepocitinib with placebo at 24 weeks were published by King et al. (2021).||2|
|Phase 2 clinical candidate for RA (NCT02969044). In this study oral treatment with ritlecitinib (200 mg once daily) was well tolerated, and was associated with significant improvements in RA disease activit.y||4|