JNK3

c-Jun N-terminal kinase 3 (JNK3) is a stress-activated protein kinase predominantly expressed in neurons, pancreatic β-cells, and cardiac tissue^[1]^[2]. Mechanistically, JNK3 modulates transcriptional programs by phosphorylating c-Jun and regulating downstream factors such as Forkhead BoxO3A (FoxO3A) and Insulin Receptor Substrate 2 (IRS2), thereby maintaining cell survival under stress conditions^[3]^[2]. In neuronal models, JNK3 contributes to axonal injury signaling and apoptosis, with combined JNK2/3 deficiency markedly reducing retinal ganglion cell death, highlighting its role in neurodegenerative processes^[4]^[5]. Compared with ubiquitously expressed JNK1 and JNK2, JNK3 demonstrates nuclear localization in β-cells and isoform-specific protective effects against cytokine-induced apoptosis^[2]^[3]. In the hypothalamus, JNK3 influences energy homeostasis by counteracting JNK1-mediated feeding and weight gain, illustrating its unique physiological role among isoforms^[6]^[7]. JNK3 activation is scaffold-dependent, particularly via arrestin-3, enabling specific phosphorylation by upstream MKK4/7 kinases and contributing to selective signal propagation^[8]. Structurally selective inhibitors targeting JNK2/3 demonstrate that hydrophobic pocket residues, including L144 in JNK3, determine isoform-specific binding, providing tools for experimental modulation of neuroprotection and β-cell survival^[9]^[10]. Overall, JNK3 serves as a critical mediator of stress responses, with distinct subcellular localization and signaling effects compared with JNK1/2, making it a valuable target for studying neurodegeneration and metabolic regulation.

References:

[1]. Nogueiras R, et al. Brain JNK and metabolic disease. Diabetologia. 2021 Feb;64(2):265-274. [Content Brief]

[2]. Abdelli S, et al. JNK3 is abundant in insulin-secreting cells and protects against cytokine-induced apoptosis. Diabetologia. 2009 Sep;52(9):1871-80. [Content Brief]

[3]. Nakano R, et al. Biological Properties of JNK3 and Its Function in Neurons, Astrocytes, Pancreatic β-Cells and Cardiovascular Cells. Cells. 2020 Jul 29;9(8):1802. [Content Brief]

[4]. Abdelli S, et al. JNK3 maintains expression of the insulin receptor substrate 2 (IRS2) in insulin-secreting cells: functional consequences for insulin signaling. PLoS One. 2012;7(5):e35997. [Content Brief]

[5]. Zhan X, et al. Arrestin-dependent activation of JNK family kinases. Handb Exp Pharmacol. 2014;219:259-80. [Content Brief]

[6]. Fernandes KA, et al. JNK2 and JNK3 are major regulators of axonal injury-induced retinal ganglion cell death. Neurobiol Dis. 2012 May;46(2):393-401. [Content Brief]

[7]. Ries V, et al. JNK2 and JNK3 combined are essential for apoptosis in dopamine neurons of the substantia nigra, but are not required for axon degeneration. J Neurochem. 2008 Dec;107(6):1578-88. [Content Brief]

[8]. Park H, et al. Structural basis and biological consequences for JNK2/3 isoform selective aminopyrazoles. Sci Rep. 2015 Jan 27;5:8047. [Content Brief]

[9]. Solinas G, et al. JNK at the crossroad of obesity, insulin resistance, and cell stress response. Mol Metab. 2016 Dec 8;6(2):174-184. [Content Brief]

[10]. Wydra VR, et al. A \"Ligand First\" Approach toward Selective, Covalent JNK2/3 Inhibitors. J Med Chem. 2025 Jun 12;68(11):12004-12028. [Content Brief]

JNK3 Related Products (48):

By Type:	Pan (23) Selective (15)
By Effects:	Inhibitors (46) Activator (1)

Cat. No.	Product Name	Effect	Purity

HY-12041

SP600125	Inhibitor	99.55%
SP600125 is an orally active, reversible, and ATP-competitive JNK inhibitor with IC₅₀s of 40, 40 and 90 nM for JNK1, JNK2 and JNK3, respectively. SP600125 is a potent ferroptosis inhibitor. SP600125 induces the transformation of bladder cancer cells from autophagy to apoptosis.

HY-13319

JNK-IN-8	Inhibitor	99.67%
JNK-IN-8 (JNK Inhibitor XVI) is a potent JNK inhibitor with IC₅₀s of 4.7 nM, 18.7 nM, and 1 nM for JNK1, JNK2, and JNK3, respectively.

HY-107598

JNK Inhibitor VIII	Inhibitor	99.58%
JNK Inhibitor VIII (TCS JNK 6o) is a c-Jun N-terminal kinases (JNK-1, -2, and -3) inhibitor with K_i values of 2 nM, 4 nM, 52 nM, respectively, and has IC₅₀ values of 45 nM and 160 nM for JNK-1 and -2, respectively.

HY-14761

Bentamapimod	Inhibitor	99.23%
Bentamapimod (AS 602801) is an ATP-competitive JNK inhibitor with IC₅₀ of 80 nM, 90 nM, and 230 nM for JNK1, JNK2, and JNK3, respectively.

HY-15495

Tanzisertib	Inhibitor	99.98%
Tanzisertib (CC-930) is a potent JNK1/2/3 inhibitor with IC₅₀s of 61/7/6 nM, respectively.

HY-181993

JNK3-IN-11	Inhibitor
JNK3-IN-11 is a selective JNK3 inhibitor with an IC50 of 2.08 nM. JNK3-IN-11 binds to the JNK3 ATP-binding pocket, forming conserved hydrogen bonds with Met149 and a water-mediated hydrogen bond with Lys93. JNK3-IN-11 suppresses TGF-β1-induced c-Jun phosphorylation, reduces profibrotic markers COL1A1 and PAI-1, restores E-cadherin expression, and has protection against podocyte injure. JNK3-IN-11 can be used for the research of chronic kidney disease.

HY-181160

JNK3/Wnt/β-catenin modulator-1	Inhibitor
JNK3/Wnt/β-catenin modulator-1 is a brain-penetrant JNK3 inhibitor and Wnt/β-catenin activator. JNK3/Wnt/β-catenin modulator-1 decreases Aβ_1-42 production and reduced ROS generation. JNK3/Wnt/β-catenin modulator-1 inhibits the activation of JNK and Puma, promotes Beclin-1 expression, reduces GSK-3β and BACE1 expression and activates Wnt/β-catenin signaling. JNK3/Wnt/β-catenin modulator-1 improves cognitive and memory performance, attenuates histopathological brain damage, preserves structure of hippocampal pyramidal cells and cerebral cortical neurons. JNK3/Wnt/β-catenin modulator-1 can be used for the research of Alzheimer's disease.

HY-12041G

SP600125 (GMP)	Inhibitor
SP600125 (GMP) is SP600125 (HY-12041) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. SP600125 is an orally active, reversible, and ATP-competitive JNK inhibitor with IC₅₀s of 40, 40 and 90 nM for JNK1, JNK2 and JNK3, respectively. SP600125 is a potent ferroptosis inhibitor. SP600125 induces the transformation of bladder cancer cells from autophagy to apoptosis.

HY-15617

JNK-IN-7	Inhibitor	98.17%
JNK-IN-7 is a potent JNK inhibitor with IC₅₀ of 1.5, 2 and 0.7 nM for JNK1, JNK2 and JNK3, respectively.

HY-11010

AS601245	Inhibitor	98.19%
AS601245 is an orally active, selective, ATP competitive JNK (c-Jun NH2-terminal protein kinase) inhibitor with IC₅₀s of 150, 220, and 70 nM for three JNK human isoforms (hJNK1, hJNK2, and hJNK3), respectively. AS601245 exhibits 10- to 20-fold selectivity over c-src, CDK2, and c-Raf and more than 50- to 100-fold selectivity over a range of Ser/Thr- and Tyr-protein kinases. Neuroprotective properties.

HY-15881

TCS JNK 5a	Inhibitor	99.40%
TCS JNK 5a is a potent JNK3 inhibitor with a pIC₅₀ of 6.7. TCS JNK 5a also inhibits JNK2 with a pIC₅₀ of 6.5.

HY-W1000105

Geranial	Inhibitor	99.51%
Geranial is an aromatic compound. It can be isolated from the fruits of Litsea cubeba Lour and the rhizomes of ginger (Zingiber officinale). Geranial inhibits LPS-induced phosphorylation of ERK1/2, JNK1/3 and IκB in macrophages. It suppresses the secretion of IL-1β, TNF-α and IL-6, as well as the expression of pro-IL-1β, iNOS and COX-2. Geranial increases ROS. It can be used in the research of inflammatory diseases.

HY-139254

Indirubin-3′-oxime	Inhibitor	99.10%
Indirubin-3′-oxime (IDR3O), a synthetic derivative of indirubin, is a potent inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase 3β (GSK3β). Indirubin-3′-oxime directly inhibits the activity of all three isoforms of JNK (JNK1, JNK2, and JNK3), with IC₅₀s of 0.8 μM, 1.4 μM, and 1.0 μM, respectively. Indirubin-3′-oxime can enhance height growth via activation of Wnt/β-catenin signaling in chondrocytes.

HY-167832

PT109	Inhibitor	99.20%
PT109 is an orally active, blood-brain barrier permeable multi-kinase inhibitor. By inhibiting PTBP1, PT109 promotes the switch of pyruvate kinase isoform from PKM2 to PKM1, thereby effectively inhibiting the proliferation and migration of glioblastoma multiforme and inducing its reprogramming into oligodendrocytes. PT109 also targets and regulates key signaling molecules such as JNK, SGK1, GSK3β to exert neuroprotective effects including promoting neurogenesis, inducing synapse formation and alleviating neuroinflammation. In Alzheimer's disease models, PT109 exhibits significant efficacy in improving spatial learning ability, along with excellent in vivo pharmacokinetic properties. PT109 can be used to investigate metabolic reprogramming of glioblastoma multiforme and neuroprotective mechanisms of Alzheimer's disease.

HY-W668775

Quin-C7		99.76%
Quin-C7 is an orally active FPR2/ALX antagonist. Quin-C7 binds to the orthosteric ligand-binding pocket of FPR2/ALX, modulates receptor activation, and inhibits pro-inflammatory ERK signaling mediated by serum amyloid A (SAA). Quin-C7 reduces pro-inflammatory mediators TNF-α levels, increases anti-inflammatory IL-10, decreases inflammatory neutrophils and pro-inflammatory M1 macrophages, downregulates ERK1/2 phosphorylation, and upregulates JNK1/2/3 phosphorylation. Quin-C7 blocks FPR2/mFpr2 signaling, reduces brain lesion volume. Quin-C7 can be used for the research of inflammatory bowel disease and neuromyelitis optica spectrum disorder.

HY-151929

JNK3 inhibitor-4	Inhibitor	99.37%
JNK3 inhibitor-4 is a potent and BBB-permeable inhibitor of JNK3 (IC₅₀=1.0 nM) based on 2-aryl-1-pyrimidinyl-1H-imidazole-5-yl acetonitrile. JNK3 inhibitor-4 shows excellent selectivity over other protein kinases including isoforms JNK1 (IC₅₀=143.9 nM) and JNK2 (IC₅₀=298.2 nM). JNK3 inhibitor-4 has neuroprotective effect and predicated blood-brain barrier permeability.

HY-107596

SR-3576	Inhibitor	99.75%
SR-3576 is a highly potent and selective JNK3 inhibitor with an IC₅₀ of 7 nM.

HY-125838

J30-8	Inhibitor	99.51%
J30-8 is a potent and isoform-selective inhibitor of c-Jun N-terminal kinase 3 (JNK3) with an IC₅₀ of 40 nM, which 2500-fold isoform selectivity against JNK1α1 and JNK2α2. J30-8 exhibits neuroprotective activity in vitro and potential for the treatment of neurodegenerative diseases.

HY-100233

IQ-1S free acid	Inhibitor	99.28%
IQ-1S free acid is a prospective inhibitor of NF-κB/activating protein 1 (AP-1) activity with an IC₅₀ of 2.3±0.41 μM. IQ-1S free acid has binding affinity (K_d values) in the nanomolar range for all three JNKs with K_ds of 100 nM, 240 nM, and 360 nM for JNK3, JNK1, and JNK2, respectively.

HY-107600

IQ-3	Inhibitor	99.61%
IQ-3 is a specific inhibitor of the c-Jun N-terminal kinase (JNK) family, with preference for JNK3. IQ-3 exhibits K_d values of 0.24 μM, 0.29 μM and 0.066 μM for JNK1, JNK2 and JNK3, respectively.

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