JIP-1(153-163) (TI-JIP) is a peptide inhibitor of c-JNK, based on residues 153-163 of JNK-interacting protein-1 (JIP-1) (Modifications: Phe-11 = C-terminal amide)[1].
[D-Arg1,D-Phe5,D-Trp7,9,Leu11]-Substance P, a Substance P derivative, is a biased agonist toward neuropeptide and chemokine receptors. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-Substance P activates G12. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-Substance P binds to IL-8 and GRP receptors. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-Substance P inhibits ERK-2 activation, activates JNK activity. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-Substance P stimulates an increase in neutrophil migration and Ca2+ mobilization. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-Substance P is also a bombesin antagonist, and inhibits the growth of small cell lung cancer[1][2][3]
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.
Isodorsmanin A is an anti-inflammatory agent. Isodorsmanin A suppresses the production of inflammatory mediators and proinflammatory cytokines. Isodorsmanin A inhibits the phosphorylation of JNK, MAPK[1].
(E)-Osmundacetone is the isomer of Osmundacetone. Osmundacetone significantly suppresses the phosphorylation of MAPKs, including JNK, ERK, and p38 kinases. Osmundacetone has a neuroprotective effect against oxidative stress[1].
SU3327 is a potent, selective and substrate-competitive JNK inhibitor with an IC50 of 0.7 μM. SU3327 also inhibits protein-protein interactions between JNK and JNK Interacting Protein (JIP) with an IC50 of 239 nM. SU3327 shows less active against p38α and Akt kinase[1][2].
JNK-IN-8 is a potent JNK inhibitor with IC50s of 4.7 nM, 18.7 nM, and 1 nM for JNK1, JNK2, and JNK3, respectively.
Urolithin B is one of the gut microbial metabolites of ellagitannins, and has anti-inflammatory and antioxidant effects. Urolithin B inhibits NF-κB activity by reducing the phosphorylation and degradation of IκBα, and suppresses the phosphorylation of JNK, ERK, and Akt, and enhances the phosphorylation of AMPK. Urolithin B is also a regulator of skeletal muscle mass[1][2].
Tanzisertib (CC-930) is a potent JNK1/2/3 inhibitor with IC50s of 61/7/6 nM, respectively.
Emodic acid (NSC624610) is an anthraquinone compound isolated from A. microcarpus, which can inhibit the proliferation of cancer cells by inhibiting the activity of NF-κB. Emodic acid can also inhibit the phosphorylation of p38, ERK and JNK, the secretion of tumor-promoting cytokines IL-1β and IL-6, and the expression of VEGF and MMP, thereby inhibiting the invasion and migration potential of cancer cells[1].
epi-Eriocalyxin A (Epieriocalyxin A), a diterpenoid isolated from Isodon eriocalyx, induces colon cancer apoptosis. epi-Eriocalyxin A also inhibits ERK1/2 and JNK activation, which suppresses Bcl-2 expression[1].
Isovitexin is a flavonoid isolated from rice hulls of Oryza sativa, possesses anti-inflammatory and anti-oxidant activities; Isovitexin acts like a JNK1/2 inhibitor and inhibits the activation of NF-κB.
SY-LB-35 is a potent bone morphogenetic protein (BMP) receptor agonist. SY-LB-35 can stimulate significant increases in cell number and cell viability in the C2C12 myoblast cell line, and causes shifts towards the S and G2/M phases of the cell cycle. SY-LB-35 stimulates canonical Smad and non-canonical PI3K/Akt, ERK, p38 and JNK intracellular signaling pathways[1].
IQ-1 is a prospective inhibitor of NF-κB/activating protein 1 (AP-1) activity with an IC50 of 2.3±0.41 μM. IQ-1 has binding affinity (Kd values) in the nanomolar range for all three JNKs with Kds of 100 nM, 240 nM, and 360 nM for JNK3, JNK1, and JNK2, respectively.
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.
JNK Inhibitor VIII (TCS JNK 6o) is a c-Jun N-terminal kinases (JNK-1, -2, and -3) inhibitor with ki values of 2 nM, 4 nM, 52 nM, respectively[1].
TOPK-p38/JNK-IN-1 (Compound B12) is an orally active TOPK-p38/JNK signaling pathway inhibitor with the IC50 value of 2.14 µM for NO production. TOPK-p38/JNK-IN-1 shows anti-inflammatory activities. TOPK-p38/JNK-IN-1 also inhibits phosphorylate downstream related proteins and avoids degradation of TOPK[1].
SR-3737 is potent both JNK3 and p38 inhibitor.
Dehydrocrenatidine, a β-carboline alkaloid that can be isolated from Picrasma quassioides. Dehydrocrenatidine induces cell Apoptosis by activates ERK and JNK. Dehydrocrenatidine inhibits invasion and migration of cancer cells, it also suppresses neuronal excitability to exert analgesic effects[1][2].
Astragaloside IV, an active component isolated from Astragalus membranaceus, suppresses the activation of ERK1/2 and JNK, and downregulates matrix metalloproteases (MMP)-2, (MMP)-9 in MDA-MB-231 breast cancer cells.
LL-Z1640-4 is a potent p38/JNK signaling inhibitor. LL-Z1640-4 significantly diminishes p38 and JNK activation in HCC cells transfected with MLK4 siRNA. LL-Z1640-4 markedly attenuates ROS production induced by MLK4 knockdown. LL-Z1640-4 significantly reduces the apoptotic cells in HCC cells transfected with siMLK4[1][2].
OVA-E1 peptide, is an antagonist variant of SIINFEKL [OVA (257-264). OVA-E1 peptide, activates the p38 and JNK cascades similarly in mutant and wild-type thymocytes[1].
Peruvoside is a potent inhibitor of Src, PI3K, JNK, STAT, and EGFR. Peruvoside induces apoptosis and autophagy and possesses a broad spectrum of anticancer activity in breast, lung, liver cancers and leukemia. Peruvoside is a broad-spectrum and potent antiviral activity against positive-sense RNA viruses. Peruvoside sensitizes Gefitinib (HY-50895)-resistant tumour cells (A549, PC9/gef and H1975) to Gefitinib[1][2][3][4].
DB07268 is a potent and selective JNK1 inhibitor with an IC50 value of 9 nM.
Novel antitumor agent, inducing PKR-mediated apoptosis and synergizing with IFN
Polyphyllin I is a bioactive constituent extracted from Paris polyphylla, has strong anti-tumor activity. Polyphyllin I is an activator of the JNK signaling pathway and is an inhibitor of PDK1/Akt/mTOR signaling. Polyphyllin I induces autophagy, G2/M phase arrest and apoptosis[1][2][3].
8-Hydroxyefavirenz (8-OH-EFV) is a primary metabolite of Efavirenz (HY-10572). 8-Hydroxyefavirenz induces apoptosis via a JNK- and BimEL-dependent mechanism in primary human hepatocytes. 8-Hydroxyefavirenz can be used in research of cancer[1].
Sugiol is an abietane diterpenoid, can be isolated from Calocedrus formosana bark. Sugiol has anti-inflammatory activity, could effectively reduce intracellular reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-stimulated macrophages[1].
JNK3 inhibitor-4 is a potent 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)[1]. JNK3 inhibitor-4 has neuroprotective effect and predicated blood-brain barrier permeability[1].