MAP3K Inhibitor

AZ-TAK1, an ATP-competitive small molecule inhibitor of TAK1, dephosphorylates TAK1, p38, and IκB-α in lymphoma cell lines.

Cot-IN-4 (compound 32) is a potent cancer osaka thyroid (COT) kinase inhibitor with an IC₅₀ of 6 nM. Cot-IN-4 inhibits the phosphorylation of ERK (IC₅₀: 60 nM) and inhibits TNFα release (IC₅₀: 60 nM). Cot-IN-4 also inhibits the formation of the pro-inflammatory cytokine IL-1β (IC₅₀: 0.2 μM) in Uric acid (HY-B2130)-stimulated macrophages. Cot-IN-4 can be used for the study of inflammatory diseases.

3,4-Dephostatin (Methyl-3,4-dephostatin) is an inhibitor of protein-tyrosine phosphatase (PTPase). 3,4-Dephostatin accelerates nerve growth factor (NGF)-induced neurite formation in PC12h cells. 3,4-Dephostatin sustains the NGF-induced tyrosine phosphorylation of proteins, most prominently that of mitogen-activated protein (MAP) kinase. 3,4-Dephostatin also prolongs epidermal growth factor (EGF)-induced tyrosine phosphorylation and activation of MAP kinase.

CBP-501 acetate, a cell-permeable calmodulin-binding peptide and a G2-abrogating drug candidate, inhibits the activity of multiple Ser²¹⁶-specific kinases, such as MAPKAP-K2, C-Tak1, CHK1 and CHK2, with IC₅₀ values of 0.9 μM, 1.4 μM 3.4 μM and 6.5 μM, respectively. CBP-501 acetate is used for various types of cancer.

Tpl2-IN-I functions as an inhibitor of the Tpl2 (tumour progression locus 2) kinase.

LZK-IN-1 is an orally active and selective LZK inhibitor with a K_d of 2.7 nM. LZK-IN-1 disrupts the LZK-AKT protein-protein interaction, blocks AKT autophosphorylation, and reduces the activation of the downstream JNK pathway. LZK-IN-1 inhibits the proliferation of cancer cells with MAP3K13 amplification and reduces in vivo tumor growth in xenograft mouse models. LZK-IN-1 can be used for the study of esophageal squamous cell carcinoma and head and neck squamous cell carcinoma with MAP3K13 amplification.

TAK1-IN-5 (Compound 26) is an inhibitor of the transforming growth factor-β activated kinase (TAK1) with an IC₅₀ value of 55 nM. TAK1-IN-5 can inhibit the growth of MPC-11 and H929 cells with a GI₅₀ lower than 30 nM. TAK1-IN-5 can be used in the study of multiple myeloma .

DDO3711, a PP5-recruiting phosphatase recruitment chimeras (PHORCs), is formed by connecting a small molecular apoptosis signal-regulated kinase 1 (ASK1) inhibitor to a PP5 activator through a chemical linker. DDO3711 specifically inhibits ASK1 (IC₅₀ =164.1 nM) not ASK2 (IC₅₀>20 μM). DDO3711 significantly dephosphorylates p-ASK1^T838 by recruiting PP5 and shows the ASK1-dependent antiproliferative activity. DDO3711 has anti-cancer activity and has the potential for abnormally phosphorylated oncoproteins research.

DLK-IN-2 is a selective inhibitor of DLK and neuroprotective agent. DLK-IN-2 shows no significant inhibition against CYPs 3A4, 2D6 and 2C9. DLK-IN-2 inhibits acute axonal palmitoylation of DLK, blocks DLK-dependent pro-degenerative axon-to-soma retrograde signaling and suppresses c-Jun phosphorylation. DLK-IN-2 can be used for the mechanistic study of neurodegenerative diseases.

Anti-inflammatory agent 102 (Compound 11a) is an orally active anti-inflammatory agent. Anti-inflammatory agent 102 exerts its anti-inflammatory effect by blocking the activation of the ASK1/p38 MAPKs/NF-κB signaling pathway. Anti-inflammatory agent 102 has significant anti-inflammatory activity and can inhibit the release of NO, ROS, and inflammatory factors (such as IL-6, TNF-α, IL-1β). Anti-inflammatory agent 102 can be used in the study of inflammatory diseases such as ulcerative colitis (UC).

KAI-11101 is the inhibitor for dual leucine zipper kinase (DLK, MAP3K12) with a K_i of 0.7 nM. KAI-11101 inhibits Paclitaxel (HY-B0015)-induced cJun phosphorylation (IC₅₀=95 nM) and thus inhibits the activation of MAPK pathway. KAI-11101 is blood brain barrier penetrable and can be further investigated for its neuroprotective property.

Selonsertib hydrochloride (GS-4997 hydrochloride) is an orally bioavailable enzyme inhibitor with potential anti-inflammatory, anti-tumor and anti-fibrotic activities. Selonsertib hydrochloride blocks ASK1 phosphorylation and activation by binding to the catalytic kinase domain. Selonsertib hydrochloride prevents the production of inflammatory cytokines and reduces the expression of genes associated with fibrosis. Selonsertib hydrochloride inhibits excessive apoptosis and limits cell proliferation.

Cot inhibitor-3 (Compound 33) is a potent and selective cancer osaka thyroid (COT) kinase inhibitor, with an IC₅₀ of 4 nM. Cot inhibitor-3 can be used to prevent inflammation-driven lameness.

N-Acetylgalactosaminyltransferase 4 (GALNT4) is a glycosyltransferase capable of inhibiting the activation of ASK1. By directly binding to ASK1, N-Acetylgalactosaminyltransferase 4 suppresses its N-terminal dimerization and subsequent phosphorylation, leading to robust inactivation of downstream JNK/p38 and NF-κB signals, and thereby improving the prognosis of liver surgery.

Cot-IN-5 (compound 1) is a potent ATP-competitive inhibitor of cancer osaka thyroid (COT). Cot-IN-5 can block COT kinase autophosphorylation.

Tpl2 Kinase Inhibitor 1 hydrochloride is a 3-pyridylmethylamino analog, and is a selective Tpl2 inhibitor (IC₅₀=50 nM). Tpl2 consists of COT kinase and MAP3K8. Tpl2 Kinase Inhibitor 1 hydrochloride plays an important role in the regulation of the inflammatory response and the progression of some cancers.

ASK1-IN-3 is a potent and selective ASK1 kinase inhibitor with IC₅₀ of 33.8 nM, as well as inhibits several cell cycle regulating kinases. ASK1-IN-3 has strong HepG2 cancer cells apoptosis induction and potent cell cycle arrest activities.

MAP3K1-IN-1 is an orally active and selective MAP3K1 kinase inhibitor. MAP3K1-IN-1 blocks TNFα-induced phosphorylation of IKKβ and activation of NF-κB. MAP3K1-IN-1 inhibits the growth of cancer cells. MAP3K1-IN-1 induces a decrease in phosphorylation sites of NPM1. MAP3K1-IN-1 can be used in pancreatic cancer-related research.

MSC 2032964A is an orally active, selective inhibitor for apoptosis signal-regulating kinase 1(ASK1) with IC₅₀ of 96 nM. MSC 2032964A preserves the visual responses in EAE mice model and exhibits potency in ameliorating the neuroinflammation.

TAO Kinase-IN-3 is a potent pan-TAOK (Thousand-And-One Kinase) inhibitor that specifically binds to and inhibits the kinase activities of TAOK1, TAOK2 and TAOK3 with K_d values of <0.17 nM, 0.34 nM, and 0.17 nM, respectively. TAO Kinase-IN-3 can be used to study Alzheimer's disease, primary tauopathies and related syndromes. In addition, TAO Kinase-IN-3 is also widely used in research on the mechanisms of cancer cachexia and the muscle atrophy it induces.