JAK1-IN-8, a potent JAK1 inhibitor (IC50<500 nM), compound 28, extracted from patent WO2016119700A1.

Ten01 has 5.0 nM activity against JAK1 kinase.

JAK-IN-14 is a potent and selective JAK1 inhibitor, with an IC50 of <5 μM. JAK-IN-14 is >8-fold more selective for JAK1 than JAK2 and JAK3 (Patent WO2016119700A1, compound 16).

JAK1/TYK2-IN-1 is a dual inhibitor of TYK2 and JAK1 (IC50 = 29 and 41 nM respectively).

Povorcitinib is a potent and selective inhibitor of JAK1. Povorcitinib has the potential for the research of disease selected from cutaneous lupus erythematosus (CLE) and Lichen planus (LP) (extracted from patent WO2021076124A1).

GDC-4379 is a JAK1 inhibitor that can be used for the research of asthma.

JAK2/TYK2-IN-2 is a potent and selective TYK2 inhibitor with IC50 values of 9 and 157 nM for TYK2 and JAK2, respectively. JAK2/TYK2-IN-2 has anti-inflammatory activity.

JAK1/TYK2-IN-3 is a potent, selective and orally active dual TYK2/JAK1 inhibitor with IC50 values of 6 and 37 nM, respectively. JAK1/TYK2-IN-3 also shows selectively relative to JAK2 (IC50=140 nM) and JAK3 (IC50=362 nM). JAK1/TYK2-IN-3 shows anti-inflammatory effect by regulating the expression of related TYK2/JAK1-regulated genes, as well as the formation of Th1, Th2, and Th17 cells.

JAK-IN-19 is a potent JAK inhibitor (PBMC IFNγ pIC50=7.2 and HLF Eotaxin pIC50=7.7). JAK-IN-19 has good retentive properties in the lung via mitigating being metabolized by Aldehyde Oxidase (AO), with diminished VEGFR2 selectivity (VEGFR2 pIC50=7.0, Aurora B pIC50=5.8).

Tofacitinib Prodrug-1 is an effective and oral active prodrug to mitigate the systemic adverse effects of Tofacitinib. Tofacitinib Prodrug-1 can effectively attenuate the oxazolone-induced colitis in mice model with low toxicity. Tofacitinib Prodrug-1 is a potential drug candidate for the treatment of ulcerative colitis.

Flonoltinib maleate is a potent, highly selective, dual JAK2/FLT3 inhibitor with IC50 of 0.8, 1.4, and 15 nM for JAK2, JAK2V617F, and FLT3, respectively.

AZD4604 (AZD-4604) is a potent, selective Janus-associated kinase 1 (JAK1) inhibitor with anti-inflammatory effect.

BMS-986202 (BMS 986202) is potent, selective Tyk2 inhibitor that binds to Tyk2 JH2 domain with IC50 of 0.19 nM, Ki of 0.02 nM, >10,000-fold over 273 kinases and pseudokinases; BMS-986202 demonstrated cellular activity (IL-23 IC50=12 nM) in IL-23 stimulated reporter assay (in Kit225 T cells). BMS-986202 also binds Jak1 JH2 with an IC50 of 7.8 nM, but this enzymatic binding did not lead to any functional activities, as BMS-986202 displayed an activity (IC50) of greater than 12.5 μM in the IL-2 stimulated Jak1/3-dependent cellular assay. BMS-986202 showed in vivo efficacy in mouse models of IL-23-driven acanthosis, anti-CD40-induced colitis, and spontaneous lupus.

LAS194046 (LAS-194046) is a potent, selective pan-JAK inhibitor with IC50 of 5.46/0.4/ 2.07 nM against JAK1/2/3, less potent in TYK2 activity (IC50=21.8 nM).LAS194046 is effective at blocking cytokine signaling depending on JAK1/JAK3, both in lymphocytes and monocytes, and JAK2/JAK2 in monocytes with IC50 of 16 nM, 26 nM and 37 nM, respectively.LAS194046 reduces allergen-induced airway inflammation, late asthmatic response, and phosphor-STAT activation in the rat OVA model.

NDI-031407 (NDI 031407) is a novel potent, selective TYK2 inhibitor with IC50 of 0.21 nM in radiometric assays, 20 fold selectivity over JAK3 (4.2 nM), 147 fold for JAK2 (31 nM), and 220 fold for JAK1 (46 nM).NDI-031407 has high potency in cell line and primary cell assays for TYK2-dependent cytokines (IL-12, IC50=118 nM) over TYK2-independent cytokines (GM-CSF).NDI-031407 blocks IL-23–induced STAT3 phosphorylation and IL-17A production in human CD4+ T cells.NDI-031407 inhibits disease progression in the SKG model of Spondyloarthritis (SpA).NDI-031407 suppresses systemic IL-23–induced type 3 immunity in vivo.

TD-1473 (Izencitinib, TD1473, JNJ 8398) is a potent, selective, oral gut-selective pan-JAK inhibitor with pKi of 10.0/10.0/8.8/9.5 for human recombinant JAK1, JAK2, JAK3 and TYK2.TD-1473 inhibited cytokine-induced phosphorylation of STAT1 in mouse primary colonic epithelial cells with pIC50 values for inhibition against IL-6, IFNα and IFNγ were 7.3, 6.8 and 7.0.TD-1473 demonstrated JAK inhibitory activity in ex vivo mouse colon and human IBD patient colonic tissue. TD-1473 (Izencitinib) is under development for the treatment of ulcerative colitis.

Humanin (human) (1-24-Protein humanin (human)), a small mitochondrial-derived cytoprotective polypeptide encoded by mtDNA, exhibits protective effects in several cell types against cellular stress conditions and apoptosis through regulating various signaling mechanisms, such as JAK/STAT pathway and interaction of BCL-2 family of protein.

SD-1008 is a potent JAK inhibitor. SD-1008 inhibits tyrosyl phosphorylation of STAT3, JAK2 and Src. SD-1008 also reduces STAT3-dependent luciferase activity. SD-1008 enhances apoptosis induced by Paclitaxel in ovarian cancer cells via directly blocking the JAK-STAT3 signaling pathway.

Peficitinib (ASP015K) hydrobromide is an orally active JAK inhibitor, with IC50s of 3.9, 5.0, 0.7 and 4.8 nM for JAK1, JAK2, JAK3 and Tyk2, respectively.

SJ1008030 (compound 8) is a JAK2 PROTAC which selectively degrades JAK2. SJ1008030 inhibits MHH–CALL-4 cells with an EC50 of 5.4 nM and an IC50 of 32.09 nM. SJ1008030 can be used for the research of leukemia.

VVD-118313 (compound 5a) is a potent, selective JAK1 inhibitor. VVD-118313 targets an isoform-restricted allosteric cysteine to block JAK1-dependent trans-phosphorylation and cytokine signaling. VVD-118313 can be used for research of cancer.

Peficitinib (ASP015K) hydrochloride is an orally active JAK inhibitor, with IC50s of 3.9, 5.0, 0.7 and 4.8 nM for JAK1, JAK2, JAK3 and Tyk2, respectively.