ak1

AK-1 is a sirtuin 2 (SIRT2) inhibitor (IC50:12.5 µM).that prevents hippocampal neurodegeneration in Alzheimer's disease models and induces cell cycle arrest in colon carcinoma cells.

TAK1/MAP4K2 inhibitor 1 (compound 5) is a dual kinase inhibitor of TAK1 and MAP4K2 with IC50 values of 41.1 nM and 18.2 nM, respectively.

NVS-PAK1-1 is a potent allosteric inhibitor of PAK1 with an IC 50 of 5 nM for dephosphorylated PAK1 and 6 nM for phosphorylated PAK1 as assessed. Inhibition is ATP-competitive, most likely due to indirect competition due to incompatibility of ATP binding with the DFG-out binding conformation of the allosteric compound. NVS-PAK1-1 has an IC50 of 270 nM against dephosphorylated PAK2 and 720 nM against phosphorylated PAK2 respectively [1].

JAK1/2/3 Inhibitor 1 is a potent protein kinase inhibitor.JAK1/2/3 Inhibitor 1 has antitumor activity that inhibits the growth of a variety of cancer cell lines. It inhibits the growth of cancer cells by binding to the cancer cell backbone and inhibiting the production of new proteins.

SGC-AAK1-1, a potent and selective inhibitor of AAK1 (AP2-associated kinase 1), has an IC50 of 270 nM and a Ki of 9 nM, and serves as a chemical probe.

JAK1-IN-4 is a selective JAK1 inhibitor (IC50s: 85 nM, 12.8 μM and >30 μM for JAK1, JAK2, and JAK3, respectively). JAK1-IN-4 inhibits STAT3 phosphorylation in NCI-H 1975 cells (IC50, 227 nM).

NVS-PAK1-1 is an effective and selective allosteric PAK1 inhibitor (IC50: 5 nM).

JAK1-IN-16 (compound 4l) acts as an inhibitor of JAK1/STAT3 and effectively downregulates the expression of TLR4 protein.

IRAK1/4/pan-FLT3 Kinase-IN-1 (Compound 31) is a potent inhibitor of IRAK1, IRAK4, and FLT3 kinases, demonstrating IC50 values of 5 nM for IRAK1, 0.6 nM for IRAK4, and less than 0.5 nM for FLT3. It exhibits favorable pharmacokinetic properties and holds promise for research in acute myeloid leukemia, with survival extension effects comparable to Gilteritinib.

AAK1/HDACs-IN-1 (Compound 12) is a dual inhibitor targeting AAK1 and HDACs, effectively inhibiting AAK1, HDAC1, and HDAC6, with IC50 values of 15.9, 148.6, and 5.2 nM, respectively. This compound also hinders SARS-CoV-2 infection by blocking the endocytosis of the ACE2-SARS-CoV-2 complex and the AP2M1-ACE2 interaction.

AAK1-IN-6 is an inhibitor of AP-2 associated protein kinase 1 (AAK1, IC50 = 12 nM) and exhibits antiviral activity against Dengue virus (DNEV2, EC50 = 0.24 μM) and Venezuelan equine encephalitis virus (VEEV, EC50 = 0.30 μM). AAK1-IN-6 is applicable in antiviral research.

JAK1/STAT3-IN-1 (compound 4f) functions as an anti-atopic dermatitis (AD) agent by inhibiting the JAK1/STAT3 signaling pathway. It has an IC50 value of 2.17 μM for inhibiting NO production. Additionally, JAK1/STAT3-IN-1 improves skin conditions in AD-like mice by reducing inflammatory infiltration, suppressing the expression of p-JAK1/JAK1 and p-STAT3/STAT3, and alleviating the hyperimmune response induced by MC903 (Calcipotriol).

NUAK1-IN-1 (Compound 9) is an inhibitor of NUAK1 with an IC50 of 5.012 nM, as well as a CDK4 inhibitor. It is suitable for research related to cancer, neurodevelopmental disorders, and Alzheimer's disease.

NUAK1-IN-2 (Compound 24) is an inhibitor of NUAK1 with an IC50 of 3.162 nM, as well as an inhibitor of CDK2/4/6. It is applicable in research related to cancer, neurodevelopmental disorders, and Alzheimer's disease.

IRAK1/4/pan-FLT3 Kinase-IN-2 (compound 27) is a potent dual inhibitor of IRAK1/4 and FLT3 with IC50 values of 10 nM, 0.7 nM, and < 0.5 nM, respectively. This compound enhances survival in mice models of acute myeloid leukemia.

JAK1-IN-14 (Compound12a) is a potent and selective inhibitor of JAK1, effectively inhibiting JAK1 and JAK2 with IC50 values of 12.6 nM and 135 nM, respectively. It reduces liver fibrosis levels and is applicable for research related to liver fibrosis and inflammatory diseases.

JAK1/2-IN-1 is a potent inhibitor of JAK1 and JAK2, with IC50 values of 0.4 nM and 8.1 nM, respectively. Additionally, JAK1/2-IN-1 inhibits IL-4 and IL-13, with IC50 values of 136.5 nM and 19.1 nM, respectively (WO2023244775A1; Example 33a).

TAK1-IN-5 (Compound 26) is an inhibitor of transforming growth factor-β activated kinase (TAK1) with an IC50 value of 55 nM. It effectively suppresses the growth of MPC-11 and H929 cells, with a GI50 below 30 nM. TAK1-IN-5 is a useful tool for research in multiple myeloma.

IRAK1-IN-1 (compound B8) is an orally active IRAK1 inhibitor. It suppresses IL-6 release in murine J774A cells and human THP-1 cells, with IC50 values of 4.57 μM and 6.51 μM, respectively. Additionally, IRAK1-IN-1 alleviates LPS-induced acute lung injury and DSS-induced colitis in mice.

PROTACJAK1 degrader 1 (compound 10c) is a potent and selective PROTAC JAK1 degrader with a DC50 of 214 nM. It also exhibits antitumor activity.

SGC-AAK1-1N is a potent and selective inhibitor of AAK1 (AP2 associated kinase 1), with an IC50 of 1.8 μM [1].

JAK1-IN-8, a specific inhibitor of Janus kinase 1 (JAK1, IC50<500 nM).

TAK1-IN-2 is a potent and selective TAK1 inhibitor with an IC50 of greater than 2 nM [1].

JAK1/TYK2-IN-1 is a dual inhibitor of TYK2 [IC50 = 29 nM] and JAK1 (IC50 = 41 nM).