JAK

WP-1034 is a selective JAK-STAT inhibitor that exhibits pro-apoptotic and antileukemic properties, particularly in acute myeloid leukemia (AML) models. By blocking the activation of Stat 3 and Stat 5, WP-1034 effectively induces cell cycle arrest and triggers apoptosis in affected cells. This reagent is valuable for research focused on understanding the mechanisms and therapeutic avenues in AML.

6-Demethoxytangeretin is a flavonoid compound isolated from *Citrus reticulata* with demonstrated anti-inflammatory and anti-allergic properties. It inhibits IL-6 production and the expression of related genes in human mast cells by modulating the ALK and MAPK signaling pathways. Additionally, 6-Demethoxytangeretin enhances CRE-mediated transcription in hippocampal neurons, indicating potential neuroregulatory effects.

Flonoltinib is a potent and orally active dual JAK2/FLT3 inhibitor with IC50 values of 0.7 nM for JAK2, 4 nM for FLT3, 26 nM for JAK1, and 39 nM for JAK3. It exhibits strong anti-cancer activity and is a promising candidate for the treatment of hematologic malignancies and other JAK/FLT3-driven cancers.

SJ1008030 (compound 8) TFA is a selective JAK2-targeting PROTAC that promotes proteasomal degradation of Janus kinase 2 (JAK2). It exhibits potent antiproliferative activity in MHH–CALL-4 leukemia cells, with an IC₅₀ of 5.4 nM. By effectively eliminating JAK2 protein rather than merely inhibiting its activity, SJ1008030 TFA represents a promising therapeutic strategy for JAK2-driven hematologic malignancies, particularly in leukemia research.

AJI-214 is a dual-target inhibitor that simultaneously inhibits Aurora kinase A and Janus kinase 2 (JAK2). It directly blocks Aurora A activity, disrupting T cell mitotic progression and polarity, while also inhibiting JAK2-mediated STAT3 phosphorylation, thereby suppressing the differentiation of pro-inflammatory TH1 and TH17 cells. AJI-214 holds therapeutic potential for modulating immune responses and is being investigated for the prevention and treatment of graft-versus-host disease (GVHD).

SJ1008030 (Compound 8) formic is a selective PROTAC degrader of JAK2, designed to target and eliminate JAK2 protein via the ubiquitin–proteasome pathway. It effectively inhibits the growth of MHH–CALL-4 leukemia cells with an IC₅₀ of 5.4 nM. SJ1008030 formic is a valuable tool for leukemia research and the study of JAK2-driven signaling pathways.

Itacnosertib is a selective inhibitor of JAK2, with an IC50 value of 8540 nM, and it also targets FLT3 and ACVR1 (ALK2) with an IC50 of 8 nM. This compound demonstrates significant anti-leukemic activity, making it valuable for research in hematological malignancies. Itacnosertib is utilized in studies investigating the mechanisms of JAK2-mediated signaling pathways and the development of targeted therapies for related disorders.

JAK-IN-39 is a potent inhibitor of the Janus kinase (JAK) family, specifically targeting JAK1, JAK2, and JAK3 with IC50 values of 0.05, 1.18, and 0.03 nM, respectively. This compound effectively reduces the viability of TF-1 cells and inhibits the production of pro-inflammatory cytokines, including TNFα and IFNγ, in vitro. JAK-IN-39 is valuable for research into immune regulation and potential therapeutic applications in inflammatory diseases and hematological malignancies.

JAK/HDAC-IN-3 is a dual inhibitor targeting Janus kinase (JAK) and histone deacetylases (HDAC). It exhibits potent inhibitory activity with IC50 values of 25.36 nM for JAK2, and 0.2 μM and 0.43 μM for HDAC and HDAC1, respectively. This compound is valuable for investigating the roles of JAK and HDAC pathways in cellular processes and disease models, particularly in cancer and inflammatory research.

DPPY is a potent JAK3 inhibitor with an IC50 of less than 10 nM, demonstrating high selectivity for protein tyrosine kinases including EGFR and BTK. It exhibits significant anti-proliferative activity against B-cell lymphoma cells. DPPY holds potential for research applications related to idiopathic pulmonary fibrosis (IPF) and other conditions involving aberrant JAK3 signaling.

MJ04 is a selective inhibitor targeting Janus Kinase 3 (JAK 3) with an IC50 of 2.03 nM. This compound effectively inhibits T cell differentiation and reduces pro-inflammatory cytokine production in lipopolysaccharide-induced macrophages. Additionally, MJ04 exhibits favorable pharmacokinetic properties in mice and has demonstrated the ability to promote hair growth in a dihydrotestosterone-induced model of androgenetic alopecia (AGA), showing minimal toxicity (LD50 > 2 g/kg).

AUH-6-96 is a potent JAK/STAT signaling inhibitor that effectively reduces Unpaired-induced transcriptional activity in Drosophila cells and inhibits tyrosine phosphorylation of STAT92E. It also suppresses both constitutive and IL-6-induced phosphorylation of STAT3 while decreasing levels of tyrosine-phosphorylated JAK3. Furthermore, AUH-6-96 induces apoptosis in cancer cells by downregulating anti-apoptotic genes downstream of STAT3, selectively reducing the viability of cancer cells with dysregulated JAK/STAT signaling. This compound is relevant for research pertaining to Hodgkin's lymphoma, breast cancer, and prostate cancer.

JAK3-IN-13 is a selective and orally bioavailable inhibitor of JAK3, exhibiting IC50 values of 4728, 2039, 8, and 365 nM against NK1, JNK2, JNK3, and Tyk2, respectively. This compound demonstrates significant antiproliferative effects and induces cell cycle arrest in the G0/G1 phase. JAK3-IN-13 is particularly relevant for research applications focused on tumor biology and the modulation of immune responses.

Phenylpyropene C is a JAK/STAT pathway inhibitor known to effectively inhibit interferon-gamma (IFN-γ) mediated expression of reporter genes, with an IC50 range of 5.4 to 10.8 μM. Additionally, it serves as an inhibitor of acyl-CoA, exhibiting an IC50 of 16.0 μM. This compound is valuable for research applications focusing on the modulation of immune responses and the exploration of cytokine signaling pathways.

Plodicitinib is an inhibitor of Janus tyrosine kinase 3 (JAK3) and TEC family kinases. This compound exhibits significant anti-inflammatory activity, making it valuable for research in inflammation-related disorders. It is applicable in studies exploring the modulation of immune responses and potential therapeutic interventions in autoimmune diseases.

NUAK1-IN-3 is a selective inhibitor of NUAK1 with a high potency, exhibiting an IC50 of 0.49 nM. It also demonstrates inhibitory activity against NUAK2 and JAK3 with IC50 values of 265 nM and 225 nM, respectively. This compound disrupts the NUAK1-MYPT1 signaling pathway, leading to reduced MYPT1 phosphorylation and inhibition of proliferation, migration, and invasion in triple-negative breast cancer cells. Additionally, NUAK1-IN-3 counteracts TGF-β1-induced epithelial-mesenchymal transition effects by modulating critical markers such as Snail, N-cadherin, and E-cadherin. It holds potential for exploring therapeutic strategies for triple-negative breast cancer.

YYSW001 is a selective Janus kinase 1 (JAK1) inhibitor with an IC50 of 6 nM, demonstrating significant efficacy in blocking JAK1-mediated phosphorylation of STAT6 as well as IL-6-induced phosphorylation of STAT3. This compound effectively suppresses pro-inflammatory cytokine levels, reduces paw swelling, and lowers clinical arthritis scores, thereby alleviating joint damage and diminishing bone loss. YYSW001 is particularly valuable for research related to rheumatoid arthritis and inflammation-related disorders.

JAK3-IN-20 is a selective and orally active JAK3 inhibitor, demonstrating an IC50 of 0.7473 nM. By covalently binding to JAK3 Cys909 and outcompeting ATP at the catalytic site, JAK3-IN-20 effectively blocks JAK-STAT pathway activation. This compound exhibits anti-tumor properties by inhibiting migration, proliferation, and growth of Bortezomib-resistant cancer cells, as well as inducing dose-dependent apoptosis. JAK3-IN-20 is a valuable tool for researching Bortezomib-resistant multiple myeloma.

oJak-989 is a selective inhibitor of Janus kinase 1 (JAK1), demonstrating a Ki of 2.8 nM for JAK1, 110 nM for JAK3, and 31 nM for TYK2. This compound is particularly relevant in the study of inflammatory diseases, as it may help elucidate the role of JAK1 in various pathological conditions and facilitate the development of targeted therapeutics. Research applications include investigating JAK1-mediated signaling pathways and the potential therapeutic impact on autoimmune disorders.