Evidence map›Paper›PMID 42825998›Full record

ArticleDermatology and therapy2026

Comparative Pharmacologic Characterization of Povorcitinib (INCB054707) as a Highly Selective Oral JAK1 Inhibitor.

Brittney Wass, Aidan M Fenix, Nina Zolotarjova, Alex Margulis, Guofeng Zhang, Dominic Sales, Maryanne Covington, Leandro L Santos, Chryssa Kanellopoulou, Ricardo Macarrón

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Article in Dermatology and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Brittney WassIncyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE, 19803, USA. bwass@incyte.com.ORCID http://orcid.org/0009-0003-0610-5401
Aidan M FenixIncyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE, 19803, USA.ORCID http://orcid.org/0000-0002-1564-7347
Nina ZolotarjovaIncyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE, 19803, USA.ORCID http://orcid.org/0009-0008-5035-4532
Alex MargulisIncyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE, 19803, USA.
Guofeng ZhangIncyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE, 19803, USA.ORCID http://orcid.org/0000-0001-9675-2044
Dominic SalesIncyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE, 19803, USA.
Maryanne CovingtonIncyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE, 19803, USA.
Leandro L SantosIncyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE, 19803, USA.ORCID http://orcid.org/0000-0001-9986-6047
Chryssa KanellopoulouIncyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE, 19803, USA.
Ricardo MacarrónIncyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE, 19803, USA. rmacarron@incyte.com.ORCID http://orcid.org/0000-0001-8868-2146

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathways mediate signaling by multiple cytokines and growth factors critical for inflammation and immune regulation. Povorcitinib (INCB054707) is an oral JAK1 inhibitor designed to achieve high selectivity over JAK2 and minimize off-target hematologic effects. This study comprehensively assessed the in vitro selectivity and potency of povorcitinib relative to the JAK inhibitors upadacitinib, abrocitinib, baricitinib, and tofacitinib.

methodsPovorcitinib and comparator compounds were characterized using enzymatic assays, full kinome profiling across 370 kinases, cytokine reporter assays, human whole-blood STAT phosphorylation assays, and cell viability studies.

resultsPovorcitinib demonstrated potent, selective JAK1 inhibition with minimal activity against JAK2, JAK3, and TYK2, showing ≥ 50-fold selectivity over JAK2 in most assays, exceeding that of other JAK inhibitors. Kinome screening confirmed minimal off-target activity. In cell-based assays, povorcitinib selectively inhibited interleukin (IL)-6- and IL-2-mediated JAK1 signaling with minimal inhibition of thrombopoietin (TPO)-mediated JAK2 signaling, achieving up to 52-fold functional JAK1 selectivity in cytokine reporter assays and greater than tenfold selectivity in human whole blood. In contrast, other selective JAK1 inhibitors, such as upadacitinib, displayed near-equipotent JAK1/JAK2 inhibition in whole-blood assays. Povorcitinib displayed no cytotoxicity at concentrations > 5000 nM in HEK293, HEPG2, HUVEC, and HLF cells, which are JAK-independent. Across orthogonal assays, povorcitinib consistently exhibited the highest JAK1 selectivity among the JAK inhibitors evaluated.

conclusionsThese data, together with its favorable pharmacokinetic and emerging clinical safety profile, highlight the potential for povorcitinib as a highly selective, next-generation JAK1 inhibitor.

Indexed as

Autoimmune diseasesINCB054707Inflammatory diseasesJAK1 selectivityJAK inhibitorsPovorcitinib

Identifiers

PMID42825998

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.