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.

JP-11646 is a novel potent, selective, non-ATP competitive Pim2 inhibitor with IC50 of 0.5/1/24 nM for Pim2/3/1, respectively; shows less potency for other kinases in a kinase selectivity panel; exhibits 4-760-fold greater suppression of MM proliferation and viability than ATP-competitive PIM inhibitors; significant reduces tumor burden and increases median survival in xenogeneic myeloma murine models.

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.

OX01401 (OX-01401, OX1401) is a potent, selective and cell active inhibitor of the PIM kinase family (PIM1 IC50=15.1 nM).OX01401 inhibited proliferation of two PIM-expressing leukaemic cancer cell lines, MV4-11 (IC50=0.5 uM) and PC3 cell (IC50=1.1 uM), and to reduced intracellular phosphorylated 4EBP1 protein in a concentration dependent manner.

SI-109 (SI 109) is a selective, high-affinity and cell-permeable STAT3 SH2 domain inhibitor with Ki of 9 nM, component of STAT3 degrader SD-36 (PROTAC).

SS-4 (STAT3 inhibitor SS-4) is a highly selective small molecule inhibitor of STAT3 tyrosine phosphorylation that potently inhibits GBM tumorigenesis in vitro and in vivo.SS-4 strongly and selectively inhibits STAT3 Y-705 phosphorylation in MT330 and LN229 GBM cells and inhibits their proliferation and inducs apoptosis with an IC50 of 100 nM.SS-4 increases the expression of STAT3 repressed genes, while decreasing the expression of STAT3 promoted genes.SS-4 markedly reduces the growth of GBM intracranial tumor xenografts.

Stafia-1 prodrug is the cell‐permeable prodrug of Stafia-1, suitable for cell based assays, inhibits tyrosine phosphorylation of STAT5a with selectivity over STAT5b in cultured human leukemia cells.

Stat3 inhibitor H182 is a potent, selective STAT3 inhibitor, inhibits Stat3 DNA-binding activity with IC50 of 0.66 uM.Stat3 inhibitor H182 shows selective inhibition of Stat3:Stat3 DNA-binding activity, over the inhibition of Stat1:Stat3 (IC50 of 3.4-8.3 μM), with far lower potencies against Stat1:Stat1 (IC50 > 15.8 uM) and Stat5:Stat5 activities (IC50 >19.1 uM).Stat3 inhibitor H182 irreversibly and covalently binds (KD=1.97 uM, ITC) to Stat3 key residues Cys426 and Cys468.Stat3 inhibitor H182 inhibits constitutive and ligand-induced Stat3 activation (pY705Stat3) and blocks Stat3 nuclear accumulation with no change in Stat3 protein levels in breast cancer cells, with little or no effects on pS727Stat3, Stat1, JAK2, EGFR, Shc, Erk1/2, Src, or Akt induction.Stat3 inhibitor H182 inhibited anchorage-dependent and independent growth (MDA-MB-231, IC50=1 uM), induced apoptosis, and suppressed Stat3 target gene expression in TNBC cells harboring constitutively-active Stat3.Stat3 inhibitor H182 inhibited growth of breast tumors in mice, enhanced response to radiation and prolonged survival.

STAT3 inhibitor N4 is a small molecule capable of inhibiting the STAT3 SH2 domain with IC50 of 0.57 uM, SPR KD of 1.04 uM, inhibits STAT3 dimerization and transcription in vitro and suppresses pancreatic cancer in vivo.N4 suppresses STAT3 activation in pancreatic cancer cells, suppresses pancreatic cancer cell growth, migration, and induces apoptosis.N4 (20 mg/kg, i.p.) suppresses pancreatic cancer growth, exhibits potent anti-metastatic activity in a pancreatic cancer liver metastasis mouse model, and prolongs survival of tumor-bearing mice.

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.

Prohibitin ligand 1 (Compound 22i), a cardioprotectant prohibitin ligand, induces a phosphorylation of the pro-survival factor STAT3. Prohibitin ligand 1 exhibits in vitro cardioprotectant activities at nanomolar concentrations.

MNK8 is a potent STAT3 (signal transducer and activator of transcription 3) inhibitor. MNK8 inhibits STAT3 activation and reduced its DNA binding ability. MNK8 shows good growth inhibition against hepatocellular carcinoma (HCC) cells. MNK8 induces apoptosis in HCC cells. MNK8 reduces prosurvival proteins expression and migration/invasion of HCC cells.

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.

Quercetagetin (6-Hydroxyquercetin), a flavonoid, is a moderately potent and selective, cell-permeable Pim-1 kinase inhibitor with IC50 of 0.34 μM.

IST5-002, a potent Stat5a/b inhibitor, selectively inhibits transcriptional activity of Stat5a/b (IC50s: 1.5 μM for Stat5a, 3.5 μM for Stat5b). IST5-002 inducs cell apoptotic and death of prostate cancer cells and chronic myeloid leukemia (CML) cells. IST5-002 can be used in the research of prostate cancer and chronic myeloid leukemia (CML).

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.