Signalisation JAK/STAT

CEE321 is an effective pan-JAK inhibitor with an IC50 of 54 nM. It effectively inhibits biomarkers associated with atopic dermatitis.

JAK-IN-19 inhibits JAK (pIC50: 7.2, 7.7), less so for VEGFR2 (7.0) and Aurora B (5.8).

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

STAT3-IN-35 is a STAT3 inhibitor that binds to the SH2 domain. This compound inhibits the phosphorylation of STAT3 and exhibits antiproliferative activity in triple-negative breast cancer (TNBC) cell lines. Additionally, STAT3-IN-35 has demonstrated toxicity and potent antitumor activity in TNBC xenograft models.

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

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.

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.

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

Londamocitinib (JAK1-IN-7) is a selective and potent JAK1 inhibitor with anti-inflammatory activity.

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].

Pim-1 kinase inhibitor 6 (Compound 4d) is a robust inhibitor of Pim-1 kinase, demonstrating an IC 50 of 0.46 μM. It significantly exhibits cytotoxic effects on cancer cells [1].

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

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.

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.

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