abrocitinib   Click here for help

GtoPdb Ligand ID: 9991

Synonyms: Cibinqo® | compound 25 [PMID: 29298069] | PF-04965842 | PF04965842
Approved drug PDB Ligand Immunopharmacology Ligand
abrocitinib is an approved drug (UK, Japan & EMA (2021), FDA (2022))
Compound class: Synthetic organic
Comment: Abrocitinib (PF-04965842) is a JAK inhibitor [4]. X-ray crystal structures of PF-04965842 bound to both JAK1 and JAK2 have been deposited with the Protein DataBank (accession IDs 6BBU and 6BBV respectively). We used the SMILES string supplied with the article in which the structure was declared [4] to generate our representation of the chemical structure. The IUPAC name in abrocitinib's INN record resolves to the same StdInChIKey as our structure. PubChem CID 78323835 represents the structure without specified stereochemistry.
The JAKs are immunokinases that are molecular targets of therapeutics which are used in the treatment of immune-mediated diseases.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 99.36
Molecular weight 323.14
XLogP 2.05
No. Lipinski's rules broken 0
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Canonical SMILES CCCS(=O)(=O)NC1CC(C1)N(c1ncnc2c1cc[nH]2)C
Isomeric SMILES CCCS(=O)(=O)N[C@@H]1C[C@@H](C1)N(c1ncnc2c1cc[nH]2)C
InChI InChI=1S/C14H21N5O2S/c1-3-6-22(20,21)18-10-7-11(8-10)19(2)14-12-4-5-15-13(12)16-9-17-14/h4-5,9-11,18H,3,6-8H2,1-2H3,(H,15,16,17)/t10-,11+
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Summary of Clinical Use Click here for help
Abrocitinib (PF-04965842) was advanced to clinical trials for autoimmune conditions, and reached Phase 3 evaluation for atopic dermatitis and Phase 2 for plaque psoriasis (NCT02201524). Results from the psoriasis trial have been published [1], and these indicated that PF-04965842 improved disease symptoms and was well tolerated in patients with moderate to severe psoriasis. Further development for psoriasis has been terminated by the sponsor (Pfizer) for business reasons. Development in moderate to severe atopic dermatitis is continuing in Pfizer's JAK1 Atopic Dermatitis Efficacy and Safety (JADE) program, which incluides the JADE MONO-1 (NCT03349060) and JADE MONO-2 (NCT03575871) trials. Results demonstrating significant efficacy in the JADE MONO-1 study were published in July 2020 [3], and similarly supportive results from JADE MONO-2 followed in August 2020 [2].

Abrocitinib was first approved for clinical use in 2021. Under these authorisations it is indicated as a treatment for moderate-to-severe atopic dermatitis in adult patients who are candidates for systemic therapy. The FDA's approval as a treatment for atopic dermatitis was granted in January 2022.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02201524 Study to Evaluate PF-04965842 in Patients With Moderate to Severe Psoriasis Phase 2 Interventional Pfizer
NCT03575871 Study Evaluating Efficacy and Safety of PF-04965842 in Subjects Aged 12 Years And Older With Moderate to Severe Atopic Dermatitis Phase 3 Interventional Pfizer
NCT03349060 Study to Evaluate Efficacy and Safety of PF-04965842 in Subjects Aged 12 Years And Older With Moderate to Severe Atopic Dermatitis Phase 3 Interventional Pfizer This RCT is known as the 'JADE MONO-1' trial. Results published in 2020, indicated that once daily, oral abrocitinib for 12 weeks was effective and well tolerated in trial participants with moderate-to-severe atopic dermatitis. 3
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