Synonym
AS601245; AS-601245; AS 601245.
IUPAC/Chemical Name
(Z)-2-(benzo[d]thiazol-2(3H)-ylidene)-2-(2-((2-(pyridin-3-yl)ethyl)amino)pyrimidin-4-yl)acetonitrile
InChi Key
AVLYNJZZQYEFEA-XDJHFCHBSA-N
InChi Code
InChI=1S/C20H16N6S/c21-12-15(19-25-17-5-1-2-6-18(17)27-19)16-8-11-24-20(26-16)23-10-7-14-4-3-9-22-13-14/h1-6,8-9,11,13,25H,7,10H2,(H,23,24,26)/b19-15+
SMILES Code
N#C/C(C1=NC(NCCC2=CC=CN=C2)=NC=C1)=C3SC4=CC=CC=C4N\3
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, not in water
Shelf Life
>5 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:
AS601245 is an ATP competitive JNK (c-Jun NH2-terminal protein kinase) inhibitor with IC50s of 150, 220, and 70 nM for three JNK human isoforms (hJNK1, hJNK2, and hJNK3), respectively.
In vitro activity:
Since the reduction of proliferation can be accompanied by the modulation of specific genes, this study determined the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and p21, in CaCo-2 cells. Moreover, this study found that AS601245 at the concentration of 0.1 μM was able to inhibit Jun phosphorylation in CaCo-2 cells. In Figure 2(a), the analysis of P-Jun expression revealed that the amount of P-Jun protein was reduced in cells treated with 0.1 μM AS601245. A similar result was observed in cells treated with AS601245 plus clofibrate.
Reference: PPAR Res. 2012; 2012: 269751. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349252/
In vivo activity:
In vitro kinase assay in the LPS + HI mouse group confirmed that AS601245 (40 mg/kg) treatment significantly reduced JNK activity compared to vehicle treatment at 6 and 24 h post-insult (Figure 6A). In the LPS + HI group, AS601245 treatment significantly decreased the numbers of ED1-positive activated microglia, TNF-α immunoreactivities, BBB damage and cleaved caspase 3-positive cells in the white matter 24 h post-insult compared to vehicle treatment (Figure 6B). Further immunofluorescent staining showed that AS601245 markedly decreased the p-JNK (+) cells attached to or located around the microvessels (Figure 7A), and also greatly attenuated cleaved caspase 3 expression in vascular endothelial cells (Figure 7B) and oligodendroglial progenitor cells (Figure 7C). Compared to vehicle, AS601245 treatment on P2 at a dosage of 40 mg/kg but not 20 mg/kg in the LPS + HI group significantly preserved MBP expression (Figure 8A) and markedly attenuated astrogliosis by downregulating GFAP immunoreactivities (Figure 8B) in the white matter on P11.
Reference: J Neuroinflammation. 2012 Jul 17;9:175. https://pubmed.ncbi.nlm.nih.gov/22805152/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
6.0 |
16.11 |
| DMF |
2.0 |
5.37 |
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
372.45
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. Cerbone A, Toaldo C, Pizzimenti S, Pettazzoni P, Dianzani C, Minelli R, Ciamporcero E, Roma G, Dianzani MU, Canaparo R, Ferretti C, Barrera G. AS601245, an Anti-Inflammatory JNK Inhibitor, and Clofibrate Have a Synergistic Effect in Inducing Cell Responses and in Affecting the Gene Expression Profile in CaCo-2 Colon Cancer Cells. PPAR Res. 2012;2012:269751. doi: 10.1155/2012/269751. Epub 2012 Feb 29. PMID: 22619672; PMCID: PMC3349252.
2. Wolschendorf F, Bosque A, Shishido T, Duverger A, Jones J, Planelles V, Kutsch O. Kinase control prevents HIV-1 reactivation in spite of high levels of induced NF-κB activity. J Virol. 2012 Apr;86(8):4548-58. doi: 10.1128/JVI.06726-11. Epub 2012 Feb 15. PMID: 22345467; PMCID: PMC3318643.
3. Wang LW, Tu YF, Huang CC, Ho CJ. JNK signaling is the shared pathway linking neuroinflammation, blood-brain barrier disruption, and oligodendroglial apoptosis in the white matter injury of the immature brain. J Neuroinflammation. 2012 Jul 17;9:175. doi: 10.1186/1742-2094-9-175. PMID: 22805152; PMCID: PMC3414763.
4. Carboni S, Boschert U, Gaillard P, Gotteland JP, Gillon JY, Vitte PA. AS601245, a c-Jun NH2-terminal kinase (JNK) inhibitor, reduces axon/dendrite damage and cognitive deficits after global cerebral ischaemia in gerbils. Br J Pharmacol. 2008 Jan;153(1):157-63. doi: 10.1038/sj.bjp.0707574. Epub 2007 Nov 19. PMID: 18026128; PMCID: PMC2199388.
In vitro protocol:
1. Cerbone A, Toaldo C, Pizzimenti S, Pettazzoni P, Dianzani C, Minelli R, Ciamporcero E, Roma G, Dianzani MU, Canaparo R, Ferretti C, Barrera G. AS601245, an Anti-Inflammatory JNK Inhibitor, and Clofibrate Have a Synergistic Effect in Inducing Cell Responses and in Affecting the Gene Expression Profile in CaCo-2 Colon Cancer Cells. PPAR Res. 2012;2012:269751. doi: 10.1155/2012/269751. Epub 2012 Feb 29. PMID: 22619672; PMCID: PMC3349252.
2. Wolschendorf F, Bosque A, Shishido T, Duverger A, Jones J, Planelles V, Kutsch O. Kinase control prevents HIV-1 reactivation in spite of high levels of induced NF-κB activity. J Virol. 2012 Apr;86(8):4548-58. doi: 10.1128/JVI.06726-11. Epub 2012 Feb 15. PMID: 22345467; PMCID: PMC3318643.
In vivo protocol:
1. Wang LW, Tu YF, Huang CC, Ho CJ. JNK signaling is the shared pathway linking neuroinflammation, blood-brain barrier disruption, and oligodendroglial apoptosis in the white matter injury of the immature brain. J Neuroinflammation. 2012 Jul 17;9:175. doi: 10.1186/1742-2094-9-175. PMID: 22805152; PMCID: PMC3414763.
2. Carboni S, Boschert U, Gaillard P, Gotteland JP, Gillon JY, Vitte PA. AS601245, a c-Jun NH2-terminal kinase (JNK) inhibitor, reduces axon/dendrite damage and cognitive deficits after global cerebral ischaemia in gerbils. Br J Pharmacol. 2008 Jan;153(1):157-63. doi: 10.1038/sj.bjp.0707574. Epub 2007 Nov 19. PMID: 18026128; PMCID: PMC2199388.
1: Cerbone A, Toaldo C, Minelli R, Ciamporcero E, Pizzimenti S, Pettazzoni P, Roma G, Dianzani MU, Ullio C, Ferretti C, Dianzani C, Barrera G. Rosiglitazone and AS601245 decrease cell adhesion and migration through modulation of specific gene expression in human colon cancer cells. PLoS One. 2012;7(6):e40149. doi: 10.1371/journal.pone.0040149. Epub 2012 Jun 28. PubMed PMID: 22761953; PubMed Central PMCID: PMC3386191.
2: Cerbone A, Toaldo C, Pizzimenti S, Pettazzoni P, Dianzani C, Minelli R, Ciamporcero E, Roma G, Dianzani MU, Canaparo R, Ferretti C, Barrera G. AS601245, an Anti-Inflammatory JNK Inhibitor, and Clofibrate Have a Synergistic Effect in Inducing Cell Responses and in Affecting the Gene Expression Profile in CaCo-2 Colon Cancer Cells. PPAR Res. 2012;2012:269751. doi: 10.1155/2012/269751. Epub 2012 Feb 29. PubMed PMID: 22619672; PubMed Central PMCID: PMC3349252.
3: Carboni S, Boschert U, Gaillard P, Gotteland JP, Gillon JY, Vitte PA. AS601245, a c-Jun NH2-terminal kinase (JNK) inhibitor, reduces axon/dendrite damage and cognitive deficits after global cerebral ischaemia in gerbils. Br J Pharmacol. 2008 Jan;153(1):157-63. Epub 2007 Nov 19. PubMed PMID: 18026128; PubMed Central PMCID: PMC2199388.
4: Carboni S, Hiver A, Szyndralewiez C, Gaillard P, Gotteland JP, Vitte PA. AS601245 (1,3-benzothiazol-2-yl (2-[[2-(3-pyridinyl) ethyl] amino]-4 pyrimidinyl) acetonitrile): a c-Jun NH2-terminal protein kinase inhibitor with neuroprotective properties. J Pharmacol Exp Ther. 2004 Jul;310(1):25-32. Epub 2004 Feb 26. PubMed PMID: 14988419.
