AS 602801 (Synonyms: AS-602801) |
| Catalog No.GC12882 |
A selective, orally bioavailable JNK inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 848344-36-5
Sample solution is provided at 25 µL, 10mM.
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Kinases represent one of the most popular and promising target class in drug discovery. Success in finding new therapeutics will depend on the validation of the kinase chosen with respect to the disease of interest, and on the ability of chemists to design and synthesize inhibitors. AS602801 is a potent and selective JNK inhibitor with therapeutic potential inMS and fibrosis.
In vitro: AS602801 blocked T-lymphocyte proliferation and induced apoptosis. In RRMS CD4t and CD8t cells, AS602801 induced apoptosis genes and expression of surface markers, while in RRMS CD11bt cells it induced expression of innate immunity receptors and co-stimulatory molecules [1].
In vivo: AS602801, the best JNK inhibitors identified so far, were currently evaluated in preclinical studies, based on preliminary promising results in animal model of auto-immune diseases and neuronal apoptosis [1].
Clinical trial: Recently, a phase IIa proof of concept study of the pan-JNK inhibitor bentamapimod (PGL5001, AS602801) for the treatment of inflammatory endometriosis had been terminated.
Reference:
[1] Ferrandi C, Richard F, Tavano P, Hauben E, Barbié V, Gotteland JP, Greco B, Fortunato M, Mariani MF, Furlan R, Comi G, Martino G, Zaratin PF. Characterization of immune cell subsets during the active phase of multiple sclerosis reveals disease and c-Jun N-terminal kinase pathway biomarkers. Mult Scler. 2011;17(1):43-56.
| Kinase experiment [1]: | |
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Kinase assays |
Purified kinase domains were incubated with AS602801 at two-fold dilutions over a concentration range of 100 uM to 0.006 uM or with vehicle (0.1% DMSO) in the presence of 10 uM ATP, 2.5 uCi of [γ-32P]ATP and substrate. Reactions were terminated by spotting onto nitrocellulose membranes; membrane was then washed four times to remove unbound radioactivity and dried. Transferred radioactivity was quantitated by phosphorimaging, and IC50 values were calculated by fitting the data to a sigmoidal dose-response. |
| Cell experiment [2]: | |
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Cell lines |
PANC-1, A549, A2780 cell lines |
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Preparation method |
The solubility of this compound in DMSO is >11.5 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
7.5 μM, 3 days |
|
Applications |
AS602801 had selective cytotoxic activity against neoplastic cells and had anticancer effects. AS602801 treatment induced three serum-cultured human cancer cell lines (PANC-1, pancreatic cancer; A594, lung cancer; A2780, ovarian cancer) death and accordingly decreased the number of viable cells. |
| Animal experiment [2]: | |
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Animal models |
BALB/cAJcl-nu/nu mice xenograft (PANC-1 CSLCs (primary tumors)) |
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Dosage form |
ip, 40 mg/kg daily for 10 consecutive days. |
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Application |
Systemic AS602801 treatment reduced the proportion of tumor-initiating cells within the primary tumors (PANC-1 CSLCs). |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Olusegun Williams, et al. Discovery of dual inhibitors of the immune cell PI3Ks p110δ and p110γ: a prototype for new anti-inflammatory drugs. Chem Biol. 2010 Feb 26; 17(2): 123–134. [2] Masashi Okada, et al. The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo. Oncotarget. 2016 May 10; 7(19): 27021–27032. | |
| Cas No. | 848344-36-5 | SDF | |
| Synonyms | AS-602801 | ||
| Chemical Name | 2-(1,3-benzothiazol-2-yl)-2-[2-[[4-(morpholin-4-ylmethyl)phenyl]methoxy]pyrimidin-4-yl]acetonitrile | ||
| Canonical SMILES | C1COCCN1CC2=CC=C(C=C2)COC3=NC=CC(=N3)C(C#N)C4=NC5=CC=CC=C5S4 | ||
| Formula | C25H23N5O2S | M.Wt | 457.55 |
| Solubility | ≥ 11.45mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1856 mL | 10.9278 mL | 21.8555 mL |
| 5 mM | 0.4371 mL | 2.1856 mL | 4.3711 mL |
| 10 mM | 0.2186 mL | 1.0928 mL | 2.1856 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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