Señalización JAK / STAT

Tyk2-IN-14, a small molecule inhibitor of TYK2, is significant in treating inflammatory diseases and conditions linked to hypersecretion of IFNa and interferons [1].

(3S,4R)-Tofacitinib is an less active enantiomer of Tofacitinib. Tofacitinib is a JAK3 inhibitor(IC50 : 1 nM).

Tyk2-IN-10 acts as an inhibitor of the Tyrosine Kinase 2 (Tyk2)-mediated signaling pathway, which plays a role in inflammation regulation.

JAK1-IN-9 (compound 23a) is a potent, selective inhibitor of JAK1, demonstrating an IC50 of 72 nM.

SI-109 is a potent inhibitor of STAT3 SH2 domain (Ki=9 nM),and with antitumor activity.

PF-06263276 selectively inhibits pan-JAK with IC50: JAK1 (2.2 nM), JAK2 (23.1 nM), JAK3 (59.9 nM), TYK2 (29.7 nM).

Lirucitinib is a JAK inhibitor known for its anti-inflammatory properties.

STAT3-IN-36 (compound 11g) is a tritarget inhibitor that selectively targets LRPPRC, STAT3, and CDK1, exhibiting potent anticancer activity. This compound binds to LRPPRC, STAT3, and CDK1, demonstrating more effective anticancer effects than those of TMF or Capecitabine. Additionally, STAT3-IN-36 exhibits an IC50 value of 1.8 μM in HGC27 cells.

LNK01004 is a JAK inhibitor that exhibits potent inhibitory effects on JAK1 (IC50: 10 nM), JAK2 (IC50: ＜0.51 nM), and TYK2 (IC50: 1.0 nM). It can concurrently inhibit multiple cytokine-induced p-STAT signaling pathways and is applicable for research on diseases such as atopic dermatitis.

Milpecitinib (Compound 21a) is a potent and selective Janus tyrosine kinase (JAK) inhibitor with anti-inflammatory properties. It shows promise for research in cancer and inflammatory diseases.

Tyk2-IN-20 (Example 289) is an effective inhibitor of Tyk2 with an IC50 value below 5 nM. Additionally, it inhibits JAK1, JAK2, and JAK3 with IC50 values under 100 nM. This compound is utilized for the research of inflammatory diseases.

GDC-9918 (compound GDC-9918) is an inhibitor of Janus kinases.

Cenacitinib is an effective inhibitor of Janus kinase (Janus kinase) and possesses anti-inflammatory activity.

YLIU-4-105-1 is a type II JAK2 inhibitor. Demonstrating in vivo pharmacological activity, YLIU-4-105-1 reduces splenic weight, decreases blood reticulocyte counts in a dose-dependent manner, and inhibits pSTAT5.

JAK3-IN-7 is a potent and selective JAK3 inhibitor (IC50<0.01 μM) for the treatment of rejection in organ transplantation, graft-versus-host reaction after

Lipid-derived lipoxins are produced at the site of vascular and mucosal inflammation where they down-regulate polymorphonuclear leukocyte recruitment and

JAK1-IN-19 (Compound 18) is a potent JAK1 inhibitor with IC50 values of 0.02 nM for JAK1, 0.5 nM for JAK2, 91 nM for JAK3, and 0.2 nM for TYK2. It demonstrates a higher intrinsic clearance in both rats and humans. JAK1-IN-19 is applicable for research into atopic dermatitis and other autoimmune diseases.

TYK2ligand 2 is the TYK2 ligand of PROTACTYD-68. TYD-68 is a highly potent and selective CRBN-recruiting TYK2 PROTAC degrader with a DC50 value of 0.42 nM.

JAK1/TYK2-IN-5 (compound A1) is an inhibitor of JAK1 and TYK2, exhibiting Ki values of 0.0044 nM for TYK2JH2, 0.02 nM for JAK1 JH2, 6.9 μM for JAK1 JH1, 0.79 μM for JAK2 JH1, 0.21 μM for JAK3 JH1, and 0.55 μM for TYK2JH1. Additionally, it inhibits STAT activation mediated by TYK2/JAK1, induced by IFNα.

GDC-0339: oral Pim kinase inhibitor for multiple myeloma (Kis: Pim1 - 0.03 nM, Pim2 - 0.1 nM, Pim3 - 0.02 nM), well-tolerated.

JAK3-IN-11: potent oral JAK3 inhibitor (IC50=1.7 nM), noncytotoxic, >588-fold selectivity, blocks T-cell growth; useful in autoimmune research.

JDTic, a 4-phenylpiperidine derivative distantly related to analgesics like meperidine and ketobemidone and more closely to the mu opioid antagonist alvimopan, exhibits a notably long duration of action, maintaining effects in animals for weeks following a single dose. This duration is not due to irreversible binding to the kappa opioid receptor but rather to altered activity of c-Jun N-terminal kinases. As a highly selective antagonist for the κ-opioid receptor, without influencing the μ- or δ-opioid receptors, JDTic has shown potential in animal studies for producing antidepressant and anxiolytic effects. It also demonstrates promise in treating addiction to substances such as cocaine and morphine, distinguishing itself structurally from other kappa antagonists like norbinaltorphimine.