JAK inhibitors ∼ overview∼

Figures & data

Figure 1. Intracellular signaling of cytokines/growth factor s via the JAK-STAT pathway.

Table 1. Cytokine/growth factor signaling profiles through the JAK-STAT pathway.

Cytokine family	Cytokines	JAK	STAT
Common γ	IL-2,4,7,9,15,21	JAK1, JAK3	STAT1,3,5,6
Common β	IL-3,5, GM-CSF	JAK2	STAT5
Homodimeric receptor	EPO, TPO, GH, Leptin, Prolactin	JAK2	STAT5
Type 1 interferon	IFNα,β	JAK1, Tyk2	STAT1,2,3
Type 2 interferon	IFNγ	JAK1,2	STAT1,3,5
gp130 family	IL-6,11,13,25,27,31, LIF, OSM	JAK1,2, Tyk2	STAT1,3,5
IL-10 family	IL-10,19,20,22	JAK1, Tyk2	STAT1,3,5
IL-12 family	IL-12,23	JAK2, Tyk2	STAT3,4

GM-CSF: granulocyte-macrophage colony-stimulating factor; EPO: erythropoietin; TPO: thrombopoietin; GH: growth hormone; IFN: interferon; LIF: leukemia inhibitory factor; OSM: oncostatin M.

Table 2. Characteristics of JAK inhibitors approved by PMDA and their primary doses for each indicated disease.

Drugs	The first approval year	Selectivity	half life	Hepatic or renal contraindication	RA	AS/nr-axSpA	Psoriasis/PsA	UC	AD	AA	MF/PV	COVID-19-P
Tofacitinib	2013	JAK1,2,3 > Tyk2	3 h	Child-Pugh C	5 mg BID			10 mg BID, then 5 mg BID
Ruxolitinib	2014	JAK1,2 > Tyk2	3 h								5 (10 for PV)-25 mg BID
Baricitinib	2017	JAK1,2 > Tyk2	6 h	CKD-G4	4 mg QD				4 mg QD	4 mg QD		4 mg QD
Peficitinib	2019	JAK3> JAK1,2, Tyk2	6 h	Child-Pugh C	150 mg QD
Upadacitinib	2020	JAK1> JAK2> JAK3, Tyk2	10 h	Child-Pugh C	15 mg QD	15 mg QD	15 mg QD	45 mg QD, then 15 mg QD	15 mg QD
Delgocitinib	2020	JAK1,2 > JAK3, Tyk2							topical
Filgotinib	2020	JAK1> JAK2> JAK3, Tyk2	8 h	Child-Pugh C, CKD-G5	200 mg QD			200 mg QD
Abrocitinib	2021	JAK1 > JAK2, Tyk2	5 h	Child-Pugh C					100 mg QD
Deucravacitinib	2022	Tyk2	10 h				6 mg QD for psoriasis

AS: ankylosing spondylitis; nr-axSpA: non-radiographic axial spondyloarthritis; PsA: psoriatic arthritis; UC: ulcerative colitis; AD: atopic dermatitis; AA: alopecia areata; MF: myelofibrosis; PV: polycythemia vera; COVID-19-P: COVID-19 pneumonia; BID: bis in die (twice a day); QD: quaque die (once a day); CKD: chronic kidney disease.