ritlecitinib   Click here for help

GtoPdb Ligand ID: 9559

Synonyms: compound 11 [PMID: 28139931] | example 5 [WO2015083028] | PF-06651600 | PF06651600
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Ritlecitinib (PF-06651600) is a potent, orally active, selective covalent inhibitor of Janus kinase 3 (JAK3) [5], with anti-inflammatory activity in in vivo models [4]. It is example 5 in a Pfizer patent that provides SAR for 343 analogues [1]. There are three crystal structures available for compounds reported in [5] with JAK3, but not for compound 11 (the PDB identifiers are 5TTV, 5TTU and 5TTS). Pfizer's pipeline webpage indicates that the ritlecitinib program has been discontinued.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 4
Topological polar surface area 73.91
Molecular weight 285.16
XLogP 1.92
No. Lipinski's rules broken 0
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Canonical SMILES C=CC(=O)N1CC(CCC1C)Nc1ncnc2c1cc[nH]2
Isomeric SMILES C=CC(=O)N1C[C@@H](CC[C@@H]1C)Nc1ncnc2c1cc[nH]2
InChI InChI=1S/C15H19N5O/c1-3-13(21)20-8-11(5-4-10(20)2)19-15-12-6-7-16-14(12)17-9-18-15/h3,6-7,9-11H,1,4-5,8H2,2H3,(H2,16,17,18,19)/t10-,11+/m0/s1
Immunopharmacology Comments
PF-06651600 is a JAK3 inhibitor with potential clinical utility as a therapeutic option for autoimmune diseases.
Immunopharmacology Disease
Disease X-Refs Comment References
Ulcerative colitis Disease Ontology: DOID:8577
OMIM: 266600
Orphanet: ORPHA771
Phase 2 clinical candidate for UC (NCT02958865).
Crohn's disease Disease Ontology: DOID:8778
OMIM: 266600
Orphanet: ORPHA206
Phase 2 clinical candidate for patients with moderate to severe CD (NCT03395184).
Alopecia areata Disease Ontology: DOID:986
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
Rheumatoid arthritis Disease Ontology: DOID:7148
OMIM: 180300
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 3