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.
Physicochemical Properties
| 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 | |
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| 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 |
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| 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 |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | JNK3 (pIC50 = 6.7); JNK2 (pIC50 = 6.5) | ||
| 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] | ||
| ln Vivo |
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| 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. | ||
| Animal Protocol |
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| References |
[1]. Bioorg Med Chem Lett . 2007 Mar 1;17(5):1296-301. [2]. Toxicol Lett . 2009 Aug 10;188(3):236-42. [3]. Traffic . 2009 Jun;10(6):637-47. |
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| Additional Infomation | N-(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)-1-naphthalenecarboxamide is a naphthalenecarboxamide. |
Solubility Data
| Solubility (In Vitro) |
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| 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. 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. 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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |