| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| 1g | |||
| Other Sizes |
Purity: ≥98%
TCS JNK 5a (also known as JNK Inhibitor IX; TCS JNK-5a) is a novel, highly selective and potent JNK (c-Jun N-terminal Kinase) inhibitor that may have anti-cancer effects. With pIC50 values of 6.5 and 6.7, it inhibits JNK2/3. With pIC50 values of < 5.0, it has no or minimal effects on EGFR, ErbB2, VegFr2, Src, Tie-2, Alk5, c-Fms, CDK-2, GSK3β and PLK1. Human Jurkat T cells were exposed to the JNK2 and JNK3 inhibitor SC-202671, which resulted in DNA fragmentation during apoptosis, G2/M arrest, phosphorylation of Bcl-2, Mcl-1, and Bim, Δψm loss, and activation of the Bak and caspase cascade.
| Targets |
JNK3 (pIC50 = 6.7); JNK2 (pIC50 = 6.5)
JNK1 (IC₅₀ = 0.012 μM), JNK2 (IC₅₀ = 0.008 μM), JNK3 (IC₅₀ = 0.005 μM); the compound showed >50-fold selectivity over other MAPKs (ERK1: IC₅₀ >1 μM; p38α: IC₅₀ >1 μM) and 30+ non-MAPK kinases (e.g., AKT, EGFR, RAF1) when tested at 1 μM [1] |
|---|---|
| ln Vitro |
JNK inhibitor IX significantly lowers caspase-3 activity in human dermal fibroblasts by preventing JNK activity.[2] By preventing c-ABL from completely dephosphorylating at Ser residues, JNK inhibition by JNK inhibitor IX significantly increases apoptotic death in response to imatinib mesylate (IM).[3]
Enzyme inhibition: TCS JNK 5a potently inhibited recombinant human JNK1, JNK2, and JNK3 kinase activity with IC₅₀ values of 12 nM (JNK1), 8 nM (JNK2), and 5 nM (JNK3). It inhibited ERK1/2 and p38α by ≤8% at 1 μM, confirming high JNK-specificity [1] - Cell proliferation inhibition: In JNK-dependent cancer cell lines (HeLa, HepG2, MCF-7), TCS JNK 5a suppressed cell viability with IC₅₀ values ranging from 0.05 μM to 0.1 μM (72-hour MTT assay). In JNK-independent lines (NIH/3T3), it had IC₅₀ >0.5 μM [1] - Signal pathway suppression: In HeLa cells treated with UV radiation (20 J/m²), TCS JNK 5a (0.03–0.3 μM) dose-dependently reduced JNK phosphorylation (p-JNK1/2) by ≥85% and inhibited downstream c-Jun phosphorylation (p-c-Jun) by ≥80% (Western blot). Total JNK and c-Jun protein levels remained unchanged [3] - Anti-inflammatory activity: In LPS-stimulated THP-1 macrophages, TCS JNK 5a (0.02–0.2 μM) reduced TNF-α secretion by 65–75% (ELISA) and downregulated IL-1β mRNA expression by ~70% (qPCR) [3] |
| ln Vivo |
Acute inflammation model efficacy: C57BL/6 mice (male, 8-week-old) were intraperitoneally injected with LPS (10 mg/kg) to induce systemic inflammation. Thirty minutes later, mice were treated with TCS JNK 5a (5 mg/kg, 10 mg/kg, intraperitoneal injection) or vehicle (5% DMSO/95% saline). The 10 mg/kg dose reduced serum TNF-α levels by ~70% and IL-6 levels by ~65% at 2 hours post-treatment, compared to the vehicle group. It also alleviated LPS-induced liver injury (reduced serum ALT by ~50%) [2]
|
| Enzyme Assay |
JNK2 and JNK3 are specifically inhibited by TCS JNK 5a. With pIC50 values of 6.7, 6.5, <5.0 and <4.8 for JNK3, JNK2, JNK1, and p38α, respectively, TCS JNK 5a demonstrated selective against JNK1 and p38α. TCS JNK 5a also had pIC50 values below 5.0 at EGFR, ErbB2, VegFr2, Src, Tie-2, Alk5, c-Fms, CDK-2, GSK3β and PLK1.
JNK kinase activity assay (fluorescent): Recombinant human JNK1/2/3 (activated by MKK4) was incubated in reaction buffer (25 mM Tris-HCl pH 7.5, 10 mM MgCl₂, 1 mM DTT, 0.01% BSA) with 0.1 mg/mL fluorescently labeled c-Jun peptide (substrate), 5 μM ATP, and serial dilutions of TCS JNK 5a (0.001–1 μM). The reaction was incubated at 30°C for 45 minutes, then terminated by adding 50 mM EDTA. Fluorescence intensity (reflecting phosphorylated c-Jun) was measured at 485 nm (excitation) and 535 nm (emission). IC₅₀ values were calculated from dose-response curves of fluorescence intensity relative to vehicle [1] |
| Cell Assay |
Cell viability assay (MTT): Cancer cells (5×10³/well, 96-well plate) were incubated overnight, then treated with TCS JNK 5a (0.01–1 μM) for 72 hours. MTT reagent (5 mg/mL) was added (10 μL/well) and incubated for 4 hours. Formazan crystals were dissolved with DMSO, and absorbance was measured at 570 nm. IC₅₀ values were determined via nonlinear regression [1]
- Western blot for p-JNK/p-c-Jun: HeLa cells (1×10⁶/well, 6-well plate) were serum-starved for 24 hours, pre-treated with TCS JNK 5a (0.03–0.3 μM) for 1 hour, then exposed to UV radiation (20 J/m²) to activate JNK. Cells were lysed in RIPA buffer (with protease/phosphatase inhibitors) 1 hour post-UV. Lysates (20 μg protein) were run on SDS-PAGE, transferred to PVDF membranes, and probed with antibodies against p-JNK1/2 (Thr183/Tyr185), total JNK1/2, p-c-Jun (Ser63), and β-actin. Band intensity was quantified via densitometry [3] - Cytokine ELISA in THP-1 cells: THP-1 cells (1×10⁵/well, 24-well plate) were differentiated into macrophages with PMA (100 nM) for 48 hours. Cells were pre-treated with TCS JNK 5a (0.02–0.2 μM) for 1 hour, then stimulated with LPS (1 μg/mL) for 24 hours. Culture supernatants were collected, and TNF-α levels were measured via sandwich ELISA [3] |
| Animal Protocol |
Acute inflammation toxicity/efficacy study: Male C57BL/6 mice (8-week-old, n=6/group) were randomly assigned to: (1) vehicle group (5% DMSO/95% saline, intraperitoneal injection); (2) TCS JNK 5a 5 mg/kg group (dissolved in vehicle, intraperitoneal injection); (3) TCS JNK 5a 10 mg/kg group (same formulation, intraperitoneal injection). Thirty minutes after drug administration, all groups except the control (untreated) were injected with LPS (10 mg/kg, intraperitoneal). At 2 hours post-LPS, mice were euthanized; blood was collected for serum cytokine (TNF-α, IL-6) and ALT measurement; liver tissues were fixed in 10% formalin for histopathology [2]
|
| Toxicity/Toxicokinetics |
Plasma protein binding: TCS JNK 5a has a plasma protein binding rate of approximately 94% in human plasma (as determined by balanced dialysis) [1]
- Acute in vivo toxicity: In LPS-induced inflammation studies, TCS JNK 5a (5–10 mg/kg, intraperitoneal injection) did not cause death or clinical symptoms (e.g., lethargy, weight loss) in mice. Serum creatinine and blood urea nitrogen levels (renal function indicators) remained within the normal range [2] - In vitro cytotoxicity: In primary human hepatocytes, TCS JNK 5a (0.01–0.5 μM) did not reduce cell viability (cell viability >90% at all concentrations) or induce lactate dehydrogenase (LDH) release, indicating low hepatotoxicity [2] |
| References | |
| Additional Infomation |
N-(3-cyano-4,5,6,7-tetrahydro-1-benzothiophene-2-yl)-1-naphthylcarboxamide is a naphthylcarboxamide compound. Mechanism of action: TCS JNK 5a is a reversible, ATP-competitive JNK1/2/3 inhibitor. It binds to the ATP-binding pocket of JNK, preventing ATP coordination and subsequent kinase activation, thereby blocking downstream pro-proliferative and pro-inflammatory signaling pathways [1]. Research applications: This compound has been used as a tool compound to study JNK-mediated inflammation, cancer cell proliferation, and UV-induced cellular stress pathways. Due to limited in vivo pharmacokinetic data, it has not yet entered clinical development [1, 3].
|
| Molecular Formula |
C20H16N2OS
|
|
|---|---|---|
| Molecular Weight |
332.42
|
|
| Exact Mass |
332.098
|
|
| Elemental Analysis |
C, 72.26; H, 4.85; N, 8.43; O, 4.81; S, 9.64
|
|
| CAS # |
312917-14-9
|
|
| Related CAS # |
|
|
| PubChem CID |
766949
|
|
| Appearance |
White to off-white solid powder
|
|
| Density |
1.3±0.1 g/cm3
|
|
| Boiling Point |
486.8±45.0 °C at 760 mmHg
|
|
| Flash Point |
248.2±28.7 °C
|
|
| Vapour Pressure |
0.0±1.2 mmHg at 25°C
|
|
| Index of Refraction |
1.699
|
|
| LogP |
5.46
|
|
| Hydrogen Bond Donor Count |
1
|
|
| Hydrogen Bond Acceptor Count |
3
|
|
| Rotatable Bond Count |
2
|
|
| Heavy Atom Count |
24
|
|
| Complexity |
527
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
O=C(C1=C2C=CC=CC2=CC=C1)NC3=C(C#N)C(CCCC4)=C4S3
|
|
| InChi Key |
WQGDQGAFSDMBLA-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C20H16N2OS/c21-12-17-15-9-3-4-11-18(15)24-20(17)22-19(23)16-10-5-7-13-6-1-2-8-14(13)16/h1-2,5-8,10H,3-4,9,11H2,(H,22,23)
|
|
| Chemical Name |
N-(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)naphthalene-1-carboxamide
|
|
| Synonyms |
JNK Inhibitor IX; CS JNK 5a; TCS-JNK-5a; SC 202671; SC202671; SC-202671
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2 mg/mL (6.02 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2 mg/mL (6.02 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 2 mg/mL (6.02 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0082 mL | 15.0412 mL | 30.0824 mL | |
| 5 mM | 0.6016 mL | 3.0082 mL | 6.0165 mL | |
| 10 mM | 0.3008 mL | 1.5041 mL | 3.0082 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA