JNK-1-IN-1

JNK-1-IN-1 is an inhibitor specifically targeting JNK-1, also exhibiting inhibition of MKK7 with an IC50 value of 7.8μM. It binds to MKK7cp, further reinforcing its role as a JNK-1 inhibitor.

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-1-IN-5 (Compound 14) is a potent JNK1 inhibitor with sub-nanomolar efficacy. It effectively inhibits TGF-β-induced epithelial-mesenchymal transition and shows promise for research targeting JNK1 as an anti-pulmonary fibrosis agent.

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.

EGFR-PK/JNK-2-IN-1 (Compound 6c) is a dual inhibitor of EGFR-PK and JNK-2, with IC50 values of 2.7 and 3.0 μM, respectively. It can induce apoptosis and cause cell cycle arrest at various stages. This compound is applicable in cancer research.

TOPK-p38/JNK-IN-1 (Compound B12) is an orally active inhibitor of the TOPK-p38/JNK signaling pathway, exhibiting an IC50 of 2.14 μM for NO production inhibition. It demonstrates anti-inflammatory properties by inhibiting downstream protein phosphorylation and preventing TOPK degradation [1].

Akt/NF-κB/JNK-IN-1 (Compound 2i) is an inhibitor of the Akt, NF-κB, and JNK signaling pathways, demonstrating inhibition of nitric oxide production (IC50: 3.15 μM) and exhibiting anti-inflammatory effects.

JNK-1-IN-2 (Compound c6) is a potent inhibitor of JNK-1 with an IC50 of 33.5 nM, and also exhibits inhibitory effects on JNK-2 and JNK-3 with IC50 values of 112.9 nM and 33.2 nM, respectively. This compound effectively inhibits the phosphorylation of c-Jun and has shown potential in reversing lung impairment, making it relevant for research into pulmonary fibrosis [1].

JNK-IN-8 (JNK Inhibitor XVI) is an irreversible JNK1/2/4 inhibitor (IC50: 4.7/18.7/1 nM) with over 10-fold selectivity compared to MNK2 and Fms, and no inhibition of Met, c-Kit, or PDGFRβ in the A375 cell line.

Astragaloside IV (AS-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. Astragaloside IV is a bioactive saponin first isolated from the dried plant roots of the genus Astragalus, which is used in traditional Chinese medicine.1 It dose-dependently inhibits human adenovirus type 3 (HAdV-3) in A549 cells (IC50 = 23 μM; LC50 = 865 μM).It inhibits replication of HAdV-3 and decreases HAdV-3-induced apoptosis. It has diverse protective effects for the cardiovascular, immune, digestive, and nervous systems. In particular, it reduces myocardial infarct size in dogs when administered prior to coronary ligation and reduces reperfusion arrhythmias in isolated rat hearts.

TASIN-1 Hydrochloride (TASIN-1 HCl) is a selective inhibitor of truncated APC that acts by selectively killing colorectal cancer cells that express truncated APC by reducing cellular cholesterol levels and inducing apoptotic cell death through the ER stress/ROS/JNK signaling in colon cancer cells.

NSC-37445 has anti-tumor activity, such as inhibits growth of bladder tumor cells in a nude mice model , prevents the recurrence and progression of non-muscle-invasive urothelial cell carcinoma. NSC-37445 can significantly reduce the expression of CDK1-inhibitory kinases, Myt1 and Wee1, and cause cyclin B1 protein accumulation leading to CDK1 activation in T24 cells. 3. Flavokawain A (Flavokavain A) may exert anti-inflammatory responses by suppressing LPS-induced expression of pro-inflammatory mediators via blockage of NF-κB-AP-1-JNK/p38 MAPK signaling pathways in the murine macrophages.

1. 2,5-Dihydroxyacetophenone (Quinacetophenone) possess anti-anxiety, and neuroprotective qualities. 2. 2,5-Dihydroxyacetophenone (Quinacetophenone) reatment can induce a sustained activation of JNK, ERK1/2, and p38 MAPKs, it also can potentiate the pro-apoptotic and anti-proliferative effects of bortezomib in U266 cells. 3. 2,5-Dihydroxyacetophenone (Quinacetophenone) has anti-inflammatory activity in activated macrophages, raising the possibility that this compound has a therapeutic potential for inflammatory conditions. 4. 2,5-Dihydroxyacetophenone (Quinacetophenone) is an uncompetitive inhibitor of murine tyrosinase (K(I) 0.28mm), it strongly inhibits both melanogenesis and cellular tyrosinase activity in vitro in 3-isobutyl-1-methylxanthin-stimulated B16 mouse melanoma cells or in vivo in zebrafish and mouse models.

GDC-0134, a dual leucine zipper kinase (DLK) inhibitor, exhibits brain penetration properties. It inhibits DLK to prevent neuronal degeneration and block JNK activation, potentially treating amyotrophic lateral sclerosis (ALS). It has been assessed in a phase 1 study aimed at treating ALS patients.

JNK-IN-21 (Compound 62) is an inhibitor of JNK-1.

JNK-IN-22 (Compound 58) is a JNK-1 inhibitor.

TLR4/JNK/NF-κB-IN-1 (Racemic-11k) is an inhibitor of TLR4, JNK, and NF-κB. It suppresses NO production in LPS-stimulated RAW264.7 cells with an IC50 of 23.2 µM. By inhibiting TLR4 expression and reducing JNK phosphorylation, TLR4/JNK/NF-κB-IN-1 prevents NF-κB activation. This leads to a decrease in the transcription of inflammation-related genes, reducing the expression of iNOS and COX-2, and the production of inflammatory mediators such as NO, PGE2, and TNF-α, thereby exhibiting anti-inflammatory activity. TLR4/JNK/NF-κB-IN-1 holds potential in the study of inflammatory diseases, including rheumatoid arthritis and various other inflammatory conditions.

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.

6-Hydroxyflavone (6-HF) is a noncompetitive inhibitors of cytochrome P450 2C9. It is a flavone, a type of chemical compound. It is reported in leaves of Barleria prionitis Linn. (a common Acanthaceae from India). 6-Hydroxyflavone may have a potential as a therapeutic drug capable for the treatment of anxiety-like disorders.

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.

Stephacidin B is a fungal metabolite that has been found inA. ochraceus.1Dimeric stephacidin B is rapidly converted to a monomer, avrainvillamide ,in vitro.2Stephacidin B is cytotoxic to a variety of cancer cells, including testosterone-independent PC3 and -sensitive LNCaP prostate cancer cells (IC50s = 0.37 and 0.06 μM, respectively) and estradiol-independent SK-BR-3 and -sensitive MCF-7 breast cancer cells (IC50s = 0.32 and 0.27 μM, respectively).1It induces apoptosis in HepG2 and Huh7 hepatocellular carcinoma cells when used at a concentration of 4 μM.3 1.Qian-Cutrone, J., Huang, S., Shu, Y.-Z., et al.Stephacidin A and B: Two structurally novel, selective inhibitors of the testosterone-dependent prostate LNCaP cellsJ. Am. Chem. Soc.124(49)14556-14557(2002) 2.Wulff, J.E., Herzon, S.B., Siegrist, R., et al.Evidence for the rapid conversion of stephacidin B into the electrophilic monomer avrainvillamide in cell cultureJ. Am. Chem. Soc.129(16)4898-4899(2007) 3.Hu, L., Zhang, T., Liu, D., et al.Notoamide-type alkaloid induced apoptosis and autophagy via a P38/JNK signaling pathway in hepatocellular carcinoma cellsRSC Adv.9(34)19855-19868(2019)

1. Cucurbitacin IIb is one of the major active compounds in Hemsleyadine tablets which have been used for clinical treatment of bacillary dysentery, enteritis and acute tonsilitis. 2. Cucurbitacin IIb exhibits its anti-inflammatory activity through modula

1. beta-Asarone (Cis-Isoelemicin) may be a potential preventive drug for Alzheimer's disease. 2. Beta-Asarone prevents autophagy and synaptic loss by reducing ROCK expression in SAMP8 mice. 3. The co-administration of beta-Asarone(Cis-Isoasarone) and l-dopa may contribute to the treatment of 6-OHDA-induced damage in rats by inhibiting autophagy activity. 4. Beta-Asarone exhibits anti-inflammatory effects by suppressing the production of pro-inflammatory mediators through NF-κB signaling and the JNK pathways in activated microglial cells and might be developed as a promising candidate to treat various neuroinflammatory diseases.