Synonym
TCS-JNK-6o; TCS JNK-6o; TCS-JNK 6o; c-Jun N-terminal Kinase Inhibitor VIII; JNK Inhibitor VIII
IUPAC/Chemical Name
N-(4-Amino-5-cyano-6-ethoxy-2-pyridinyl)-2,5-dimethoxybenzeneacetamide
InChi Key
KQMPRSZTUSSXND-UHFFFAOYSA-N
InChi Code
InChI=1S/C18H20N4O4/c1-4-26-18-13(10-19)14(20)9-16(22-18)21-17(23)8-11-7-12(24-2)5-6-15(11)25-3/h5-7,9H,4,8H2,1-3H3,(H3,20,21,22,23)
SMILES Code
O=C(NC1=NC(OCC)=C(C#N)C(N)=C1)CC2=CC(OC)=CC=C2OC
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
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, and has IC50 values of 45 nM and 160 nM for JNK-1 and -2, respectively.
In vitro activity:
Similar to X1, pretreatment with JNK inhibitor VIII prevented mitochondrial depolarization induced by SOR both in Huh7 and HepG2 cells (Fig. 5 A-C). These findings show that mitochondrial dysfunction after both X1 and SOR are mediated by JNK activation.
Reference: Biochem Pharmacol. 2020 Jan;171:113728. https://pubmed.ncbi.nlm.nih.gov/31759978/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
10.0 |
28.06 |
| DMSO |
91.7 |
257.20 |
| DMSO:PBS (pH 7.2) (1:2) |
0.3 |
0.84 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
356.38
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Heslop KA, Rovini A, Hunt EG, Fang D, Morris ME, Christie CF, Gooz MB, DeHart DN, Dang Y, Lemasters JJ, Maldonado EN. JNK activation and translocation to mitochondria mediates mitochondrial dysfunction and cell death induced by VDAC opening and sorafenib in hepatocarcinoma cells. Biochem Pharmacol. 2020 Jan;171:113728. doi: 10.1016/j.bcp.2019.113728. Epub 2019 Nov 21. PMID: 31759978; PMCID: PMC7309270.
2. Kluwe J, Pradere JP, Gwak GY, Mencin A, De Minicis S, Osterreicher CH, Colmenero J, Bataller R, Schwabe RF. Modulation of hepatic fibrosis by c-Jun-N-terminal kinase inhibition. Gastroenterology. 2010 Jan;138(1):347-59. doi: 10.1053/j.gastro.2009.09.015. Epub 2009 Sep 24. PMID: 19782079; PMCID: PMC2988578.
In vitro protocol:
1. Heslop KA, Rovini A, Hunt EG, Fang D, Morris ME, Christie CF, Gooz MB, DeHart DN, Dang Y, Lemasters JJ, Maldonado EN. JNK activation and translocation to mitochondria mediates mitochondrial dysfunction and cell death induced by VDAC opening and sorafenib in hepatocarcinoma cells. Biochem Pharmacol. 2020 Jan;171:113728. doi: 10.1016/j.bcp.2019.113728. Epub 2019 Nov 21. PMID: 31759978; PMCID: PMC7309270.
2. Kluwe J, Pradere JP, Gwak GY, Mencin A, De Minicis S, Osterreicher CH, Colmenero J, Bataller R, Schwabe RF. Modulation of hepatic fibrosis by c-Jun-N-terminal kinase inhibition. Gastroenterology. 2010 Jan;138(1):347-59. doi: 10.1053/j.gastro.2009.09.015. Epub 2009 Sep 24. PMID: 19782079; PMCID: PMC2988578.
1: Caly L, Li HM, Bogoyevitch MA, Jans DA. c-Jun N-terminal kinase activity is required for efficient respiratory syncytial virus production. Biochem Biophys Res Commun. 2017 Jan 29;483(1):64-68. doi: 10.1016/j.bbrc.2017.01.005. Epub 2017 Jan 4. PubMed PMID: 28062184.
2: Bertoldo MJ, Bernard J, Duffard N, Tsikis G, Alves S, Calais L, Uzbekova S, Monniaux D, Mermillod P, Locatelli Y. Inhibitors of c-Jun phosphorylation impede ovine primordial follicle activation. Mol Hum Reprod. 2016 May;22(5):338-49. doi: 10.1093/molehr/gaw012. Epub 2016 Feb 7. PubMed PMID: 26908644.
3: Turpeinen T, Nieminen R, Moilanen E, Korhonen R. Mitogen-activated protein kinase phosphatase-1 negatively regulates the expression of interleukin-6, interleukin-8, and cyclooxygenase-2 in A549 human lung epithelial cells. J Pharmacol Exp Ther. 2010 Apr;333(1):310-8. doi: 10.1124/jpet.109.157438. Epub 2010 Jan 20. PubMed PMID: 20089808.
4: Ogino T, Ozaki M, Hosako M, Omori M, Okada S, Matsukawa A. Activation of c-Jun N-terminal kinase is essential for oxidative stress-induced Jurkat cell apoptosis by monochloramine. Leuk Res. 2009 Jan;33(1):151-8. doi: 10.1016/j.leukres.2008.07.009. Epub 2008 Aug 20. PubMed PMID: 18718660.
