jnk/c-jun

IMM-H007 is a novel lipid-lowering agent, increasing abca1 protein expression

Ralimetinib is a selective inhibitor that blocks phosphorylation of MK2 at Thr334, without affecting the phosphorylation of p38α MAPK, JNK, ERK1/2, c-Jun, ATF2, or c-Myc. Ralimetinib functions as an ATP-competitive inhibitor of p38 MAPK α/β, demonstrating IC50 values of 5.3 and 3.2 nM, respectively, and is under investigation as an anti-inflammatory and anticancer therapeutic.

NBDHEX is a potent inhibitor of glutathione S-transferase P1-1 (GSTP1-1) .

MPT0B392 is an orally active quinoline derivative, induces c-Jun N-terminal kinase (JNK) activation.

JNK-1-IN-3 (Compound 9e) is a JNK1 inhibitor that downregulates JNK1 and phosphorylated JNK1, reduces c-Jun and c-Fos expression in tumours, and restores p53 activity. JNK-1-IN-3 exhibits potent antiproliferative activity against renal carcinoma and breast cancer cell lines.

JNK-1-IN-4 (Compound E1) is an inhibitor of JNK, targeting JNK-1, JNK-2, and JNK-3 with IC50 values of 2.7, 19.0, and 9.0 nM, respectively. This compound inhibits the phosphorylation of c-Jun and reduces the expression of TGF-β1-induced EMT markers (such as fibronectin and α-SMA). JNK-1-IN-4 exhibits favorable pharmacokinetic properties with a bioavailability of 69%. Additionally, it demonstrates antifibrotic effects in a Bleomycin-induced mouse model of idiopathic pulmonary fibrosis.

JNK-IN-19 (Compound Q8) is an inhibitor of c-Jun N-terminal kinase, utilized for the treatment and/or prevention of injuries prior to, during, or following surgery.

SET-171 is a JNK (c-Jun N-terminal kinase) inhibitor that exhibits significant anticancer activity by suppressing the expression of hepatic pyruvate kinase (PKL) and offers potential in regulating lipid metabolism. In antitumor studies, SET-171 shows notable cytotoxicity against human liver cancer cell lines HepG2 and Huh7, with IC50 values of 8.82 μM and 2.97 μM, respectively. Additionally, in research related to non-alcoholic fatty liver disease (NAFLD), SET-171 significantly reduces triglyceride (TAG) levels and inhibits the expression of proteins associated with steatosis. This compound holds promise for hepatocellular carcinoma (HCC) and NAFLD research.

3-AP-Me is the dimethyl derivative of the ribonucleotide reductase inhibitor 3-AP (SML0568). It activates the endoplasmic reticulum (ER) stress pathway by promoting eIF2α phosphorylation and upregulating gene expression of transcription factors ATF4 and ATF6, thereby inducing apoptosis. Additionally, 3-AP-Me activates cellular stress kinases c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase, leading to the upregulation of spliced mRNA variant XBP1. It is applicable in cancer research.

2-Pyridinamine, 4-[3-fluoro-5-(4-morpholinyl)phenyl] (Compound 9l) is an ATP-competitive JNK (c-Jun N-terminal kinase) inhibitor with IC₅₀ values of 0.099 μM and 0.148 μM for JNK1 and JNK3 respectively, exhibiting the advantage of blood-brain barrier penetration. 2-Pyridinamine, 4-[3-fluoro-5-(4-morpholinyl)phenyl] inhibits c-Jun phosphorylation and reactive oxygen species (ROS) generation, making it suitable for neurodegenerative disease research.

ZAK-IN-1 is an orally active and selective inhibitor of the leucine zipper and sterile-alpha motif kinase ZAK, with an IC50 of 4 nM and a KD of 8 nM. It demonstrates exceptional selectivity against 403 types of wild-type kinases. ZAK-IN-1 effectively blocks the p38/GATA-4 and JNK/c-Jun signaling pathways, significantly suppressing cardiac hypertrophy. This compound is applicable in the study of hypertrophic cardiomyopathy (HCM).

Ro 31-8220 formic is a potent inhibitor of protein kinase C (PKC), specifically targeting PKCα, PKCβI, PKCβII, PKCγ, PKCε, and rat brain PKC, with IC50 values of 5, 24, 14, 27, 24, and 23 nM, respectively. It also inhibits MAPKAP-K1b, MSK1, S6K1, and GSK3β, with IC50 values of 3, 8, 15, and 38 nM. Additionally, Ro 31-8220 formic suppresses the expression of MKP-1, induces c-Jun expression, and activates JNK, exhibiting these effects through mechanisms independent of PKC.

Ezatiostat hydrochloride (TLK199 HCl) is an effective inhibitor of glutathione S-transferase. Ezatiostat hydrochloride is a novel glutathione analog and the potential treatment of cytopenias. In addition, Ezatiostat hydrochloride has been revealed to selectively bind to and thus inhibit GSTP1-1.

AS601245 is an inhibitor of the c-Jun NH2-terminal kinase (JNK), with neuroprotective properties.

JNK-IN-7 (JNK inhibitor) is a selective JNK1/2/3 inhibitor (IC50: 1.54/1.99/0.75 nM). It can also inhibit phosphorylation of c-Jun, which is a substrate of JNK kinase.

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.

High affinity JNK inhibitor (Ki values are 25-50 nM). Inhibits JNK via competitive binding of the ATP-binding site of active, phosphorylated JNK. Exhibits > 40-fold selectivity for JNK over p38, ERK, IKK2, protein kinase C, Lck and ZAP70. Hepatoprotective. Also inhibits HCMV replication. Uehara et al (2004) c-Jun N-terminal kinase mediates hepatic injury after rat liver transplantation. Transplantation. 78 324 PMID:15316358 |Uehara et al (2005) JNK mediates hepatic ischemia reperfusion injury. J.Hepatol. 42 850 PMID:15885356 |Ma et al (2007) A pathogenic role for c-Jun amino-terminal kinase signaling in renal fibrosis and tubular cell apoptosis. J.Am.Soc.Nephrol. 18 472 PMID:17202416 |Ma et al (2009) Blockade of the c-Jun amino terminal kinase prevents crescent formation and halts established anti-GBM glomerulonephritis in the rat. Lab.Invest. 89 470 PMID:19188913 |Zhang et al (2015) The c-Jun N-terminal kinase inhibitor SP600125 inhibits human cytomegalovirus replication. J.Med.Virol. 87 2135 PMID:26058558 |Vasilevskaya et al (2015) Inhibition of JNK sensitizes hypoxic colon cancer cells to DNA-damaging agents. Clin.Cancer.Res. 21 4143 PMID:26023085

Pinostilbene obviously attenuates the phosphorylation of c-Jun and JNK triggered by 6-OHDA.

10-Gingerol-induced apoptosis was accompanied by phosphorylation of the mitogen-activated protein kinase (MAPKs) family, p38 MAPK (p38), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK).

Ezatiostat (TER199(free base)) is a tripeptide analog of glutathione that can selectively inhibit GSTP1-1 catalytic activity.

CC-401 Hydrochloride (CC401 HCl) is a second generation ATP-competitive anthrapyrazolone c-Jun N terminal kinase (JNK) inhibitor (Ki of 25 to 50 nM.)with potential antineoplastic activity.

Erioflorin is an ATP-competitive selective c-Jun N-terminal kinase (JNK) inhibitor.

1. Mulberroside has nephroprotective, hypoglycemic, and antidiabetic effects. 2. Mulberroside A is a glycosylated stilbene of oxyresveratrol; thus, the deglycosylation of Mulberroside A resulted in enhanced inhibition of melanogenesis. 3. Mulberroside A has anti-inflammatory antiapoptotic effects. by decreasing the expressions of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 and inhibiting the activation of NALP3, caspase-1, and nuclear factor-κB and the phosphorylation of extracellular signal-regulated protein kinases, the c-Jun N-terminal kinase, and p38.

JNK Inhibitor VIII (TCS JNK 6o) is an ATP-competitive, selective inhibitor of c-Jun N-terminal kinase (JNK) with IC50 values of 45 nM for JNK-1 and 160 nM for JNK-2.