jnk3 inhibitor 1

JNK3 inhibitor-1 is a highly potent and selective compound that specifically inhibits JNK3 with an impressive IC50 value of 0.005 μM. In addition to its remarkable inhibitory effects, JNK3 inhibitor-1 possesses excellent oral bioavailability and the ability to efficiently penetrate the brain.

JNK-IN-8 (JNK Inhibitor XVI) is an effective JNK inhibitor that inhibits JNK1, JNK2, and JNK3 with IC₅₀ values of 4.7, 18.7, and 1 nM, respectively. JNK-IN-8 offers the advantages of minimal off-target activity, sustained inhibition, and high specificity. JNK-IN-8 primarily acts by blocking the JNK/c-Jun signaling pathway, inhibiting the phosphorylation of the downstream transcription factor c-Jun, thereby regulating the expression of genes associated with inflammatory responses, apoptosis, and stress responses. JNK-IN-8 can be used in research on tumors, inflammation, and neurological diseases.

JNK3 Inhibitor-4, a potent 2-aryl-1-pyrimidinyl-1H-imidazole-5-yl acetonitrile derivative, demonstrates a strong inhibitory effect on JNK3 with an IC 50 value of 1.0 nM. It exhibits exceptional selectivity against JNK3 when compared to other protein kinases, including isoforms JNK1 (IC 50 = 143.9 nM) and JNK2 (IC 50 = 298.2 nM). Additionally, JNK3 Inhibitor-4 benefits from neuroprotective properties and is predicted to permeate the blood-brain barrier effectively.

IQ-1S is an inhibitor of NF-κB/activating protein 1 (AP-1) with an IC50 of 1.8 μM. It exhibits high binding affinity to all three JNKs, with Kd values for JNK3, JNK2, and JNK1 being 87 nM, 360 nM, and 390 nM, respectively.

BRAFV600E/JNK-IN-1 (Compound 14c) is an inhibitor of JNK1, JNK2, JNK3, and BRAFV600E, with IC50 values of 0.51 μM, 0.53 μM, 1.02 μM, and 0.009 μM, respectively. It also inhibits the phosphorylation of MEK1/2 and ERK1/2. Additionally, BRAFV600E/JNK-IN-1 suppresses tumor cell proliferation, NO release, and PGE2 production, exhibiting both antitumor and anti-inflammatory activities.

JNK-IN-17 (Compound 9J) is a selective and potent inhibitor of JNK, exhibiting IC50 values of 0.039 μM for JNK1 and 0.079 μM for JNK3. It effectively inhibits c-Jun phosphorylation in Streptozotocin-induced INS-1 pancreatic β cells, with an IC50 of 0.082 μM. JNK-IN-17 shows inhibition rates of ≤ 33% for the four major P450 isoforms (2C9, 2D6, 3A4, 1A2) in human liver microsomes, indicating a relatively low risk of drug interactions. This compound can be utilized in research on neurological and metabolic disorders, including Parkinson's disease.

JNK3/Wnt/β-catenin modulator-1 is a blood-brain barrier-penetrating inhibitor of JNK3 and an activator of the Wnt/β-catenin pathway. It reduces the generation of Aβ1-42 and the production of reactive oxygen species (ROS). This compound inhibits the activation of JNK and Puma, promotes the expression of Beclin-1, and downregulates GSK-3β and BACE1 expression, thereby activating the Wnt/β-catenin signaling pathway. JNK3/Wnt/β-catenin modulator-1 improves cognition and memory, alleviates neuropathological damage, and maintains structural integrity of hippocampal pyramidal cells and cortical neurons. It is applicable in Alzheimer’s disease research.

JNK3-IN-11 is a selective JNK3 inhibitor with an IC50 of 2.08 nM. It binds to the ATP binding pocket of JNK3, forming a conserved hydrogen bond with Met149 and a water-mediated hydrogen bond with Lys93. JNK3-IN-11 inhibits TGF-β1-induced c-Jun phosphorylation, reduces pro-fibrotic markers COL1A1 and PAI-1, restores E-cadherin expression, and protects against podocyte injury. This compound is applicable for chronic kidney disease research.

TCS JNK 5a (SC202671) is an effective, specific inhibitor of JNK3(pIC50= 6.7), JNK2(pIC50=6.5).

IQ-1S free acid (IQ-1S) is an effective and specific c-Jun N-Terminal Kinase Inhibitor. IQ-1S inhibits murine delayed-type hypersensitivity. IQ-1S can reduce inflammation and cartilage loss associated with CIA and can serve as a small-molecule modulator for mechanistic studies of JNK function in rheumatoid arthritis. IQ-1S is highly specific for JNK and that its neutral form is the most abundant species at physiologic pH.

TA-02 is a p38 MAPK inhibitor with IC50 of 20 nM.TA-02 especially inhibits TGFBR-2.

JNK-IN-11 (compound 1) is a potent inhibitor of JNK, with IC50 values of 2.2 μM, 21.4 μM, and 1.8 μM for JNK1, JNK2, and JNK3, respectively, showing potential for Alzheimer's and Parkinson's disease research.

JNK3 inhibitor-2 is a potent and selective JNK3 inhibitor with IC50 values of >100 μM for JNK1, >100 μM for JNK2, and 0.25 μM for JNK3. JNK3 inhibitor-2 also inhibits DDR1 and EGFR (T790M, L858R) [1].

JNK3 Inhibitor-3 (compound 15g) is a selective, blood-brain barrier permeable, and orally active inhibitor of c-Jun N-terminal kinase 3 (JNK3) with IC50 values of 147.8 nM, 44.0 nM, and 4.1 nM against JNK1, JNK2, and JNK3, respectively. This compound has been shown to significantly enhance memory in mouse models of dementia and is utilized in Alzheimer's disease research [1].

JNK3 inhibitor-7, a potent and orally active compound that can cross the blood-brain barrier, acts as a JNK3 inhibitor with IC50 values of 53 nM for JNK3, 973 nM for JNK2, and 1039 nM for JNK1. Demonstrating significant neuroprotective effects, JNK3 inhibitor-7 holds potential for Alzheimer's disease (AD) research [1].

JNK3 Inhibitor-8 is a potent, selective, and orally active inhibitor that can cross the blood-brain barrier, targeting JNK3 with IC50 values of 21 nM for JNK3, 2203 nM for JNK2, and >10000 nM for JNK1. This compound demonstrates significant neuroprotective effects and holds promise for Alzheimer's disease (AD) research [1].

YL5084, a covalent inhibitor selective for JNK2 and JNK3 over JNK1, demonstrates IC50 values of 70 nM and 84 nM for JNK2 and JNK3, respectively, compared to 2173 nM for JNK1. This compound also shows antiproliferative effects and induces apoptosis independently of JNK2 activity [1].

JNK-IN-14 is a potent inhibitor of JNK with IC50 values of 1.81 nM for JNK1, 12.7 nM for JNK2, and 10.5 nM for JNK3. It induces early-stage apoptosis, arrests cell population at the G2/M phase, and moderately inhibits beclin-1 production in K562 leukemia cells, demonstrating greater inhibitory efficacy than SP600125. [1]