Señalización JAK / STAT

JAK1/TYK2-IN-3, orally active, selectively inhibits TYK2 (IC50: 6 nM), JAK1 (37 nM), JAK2 (140 nM), JAK3 (362 nM), and has anti-inflammatory effects.

"JAK-IN-23: oral dual JAK/STAT & NF-κB inhibitor; JAK1 (IC50: 8.9 nM), JAK2 (15 nM), JAK3 (46.2 nM); for IBD research."

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.

iBFAR2, an inhibitor of BFAR, restores the CD8+ tumor-resident memory T cell subset against solid tumors. It promotes the binding of JAK2-STAT1 and enhances the phosphorylation of STAT1.

JAK3-IN-18 is a selective and orally active dual inhibitor targeting JAK3 and TEC, with IC50 values of 0.5391 nM and 12.40 nM, respectively. It demonstrates remarkable selectivity for AK1, AK2, and TYK2, with selectivity ratios exceeding 10,000-fold. JAK3-IN-18 exhibits exceptional therapeutic efficacy in a mouse model of experimental autoimmune encephalomyelitis and is applicable for multiple sclerosis research.

"STAT3-IN-8 (compound H172) is a potent inhibitor of STAT3 with potential applications in cancer research [1]."

JAK2-IN-18 (Compound example1) is a selective JAK2 inhibitor. It effectively inhibits the JAK-STAT signaling pathway, with an IC50 value of less than 100 nM for pSTAT5 in HEL9217 cells. JAK2-IN-18 suppresses the proliferation of abnormally proliferating myeloid cells and is useful in research on myeloproliferative disorders, such as essential thrombocythemia.

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.

CP-352664 is a JAK inhibitor with potency against JAK3, exhibiting an EC50 value of 210 nM. It holds potential for use in research related to organ transplant rejection and autoimmune diseases, such as rheumatoid arthritis.

PMMB-187, a selective STAT3 inhibitor, exhibits an IC50 of 1.81 μM in MDA-MB-231 cells. This compound induces apoptosis in MDA-MB-231 cells by inhibiting STAT3 transcriptional activity and nuclear translocation, reducing mitochondrial membrane potential, increasing reactive oxygen species (ROS) production, and upregulating the expression of apoptosis-related proteins. PMMB-187 is useful for research in the field of cancer.

KT621 Analog 2 also measured the DC50 value of STAT6 to be > 1 µM through the Meso Scale Discovery Assay (MSDA) method. This detection was derived after culturing the human cell line A549 at 37°C for 24 hours.

WZ-2-033 is a potent STAT3 inhibitor. It inhibits proliferation, colony survival, migration, and invasion of MDA-MB-231, HCC70, and MDA-MB231-4175 cells, with IC50 values of 0.7, 1.3, and 1.3 μM respectively.

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.