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TC ASK 10

Potent and selective ASK1 inhibitor; orally bioavailable CAS# 1005775-56-3

TC ASK 10

Catalog No. BCC6301----Order now to get a substantial discount!

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TC ASK 10: 5mg $138 In Stock
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Chemical structure

TC ASK 10

3D structure

Chemical Properties of TC ASK 10

Cas No. 1005775-56-3 SDF Download SDF
PubChem ID 68661090 Appearance Powder
Formula C21H23Cl2N5O M.Wt 432.35
Type of Compound N/A Storage Desiccate at -20°C
Solubility Soluble to 100 mM in water and to 100 mM in DMSO
Chemical Name 4-tert-butyl-N-(6-imidazol-1-ylimidazo[1,2-a]pyridin-2-yl)benzamide;dihydrochloride
SMILES CC(C)(C)C1=CC=C(C=C1)C(=O)NC2=CN3C=C(C=CC3=N2)N4C=CN=C4.Cl.Cl
Standard InChIKey IKKLFEDUYFZNBO-UHFFFAOYSA-N
Standard InChI InChI=1S/C21H21N5O.2ClH/c1-21(2,3)16-6-4-15(5-7-16)20(27)24-18-13-26-12-17(8-9-19(26)23-18)25-11-10-22-14-25;;/h4-14H,1-3H3,(H,24,27);2*1H
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of TC ASK 10

DescriptionPotent ASK1 inhibitor (IC50 = 14 nM); displays selectivity for ASK1 over other kinases including ASK2 (IC50 = 0.51 μM), MEKK1, TAK1, IKKβ, ERK1, JNK1, p38α, GSK-3β, PKCθ and B-raf (IC50 values are > 10 μM). Blocks downstream JNK1/p38 phosphorylation in cells. Orally bioavailable.

TC ASK 10 Dilution Calculator

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TC ASK 10 Molarity Calculator

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Preparing Stock Solutions of TC ASK 10

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.3129 mL 11.5647 mL 23.1294 mL 46.2588 mL 57.8235 mL
5 mM 0.4626 mL 2.3129 mL 4.6259 mL 9.2518 mL 11.5647 mL
10 mM 0.2313 mL 1.1565 mL 2.3129 mL 4.6259 mL 5.7824 mL
50 mM 0.0463 mL 0.2313 mL 0.4626 mL 0.9252 mL 1.1565 mL
100 mM 0.0231 mL 0.1156 mL 0.2313 mL 0.4626 mL 0.5782 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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References on TC ASK 10

Apoptosis signal-regulating kinase 1 inhibition attenuates human airway smooth muscle growth and migration in chronic obstructive pulmonary disease.[Pubmed:30006481]

Clin Sci (Lond). 2018 Jul 31;132(14):1615-1627.

Increased airway smooth muscle (ASM) mass is observed in chronic obstructive pulmonary disease (COPD), which is correlated with disease severity and negatively affects lung function in these patients. Thus, there is clear unmet clinical need for finding new therapies which can target airway remodeling and disease progression in COPD. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) activated by various stress stimuli, including reactive oxygen species (ROS), tumor necrosis factor (TNF)-alpha, and lipopolysaccharide (LPS) and is known to regulate cell proliferation. ASM cells from COPD patients are hyperproliferative to mitogens in vitro However, the role of ASK1 in ASM growth is not established. Here, we aim to determine the effects of ASK1 inhibition on ASM growth and pro-mitogenic signaling using ASM cells from COPD patients. We found greater expression of ASK1 in ASM bundles of COPD lung when compared with non-COPD. Pre-treatment of ASM cells with highly selective ASK1 inhibitor, TC ASK 10 resulted in a dose-dependent reduction in mitogen (FBS, PDGF, and EGF; 72 h)-induced ASM growth as measured by CyQUANT assay. Further, molecular targetting of ASK1 using siRNA in ASM cells prevented mitogen-induced cell growth. In addition, to anti-mitogenic potential, ASK1 inhibitor also prevented TGFbeta1-induced migration of ASM cells in vitro Immunoblotting revealed that anti-mitogenic effects are mediated by C-Jun N-terminal kinase (JNK) and p38MAP kinase-signaling pathways as evident by reduced phosphorylation of downstream effectors JNK1/2 and p38MAP kinases, respectively, with no effect on extracellular signal-regulated kinase (ERK) 1/2 (ERK1/2). Collectively, these findings establish the anti-mitogenic effect of ASK1 inhibition and identify a novel pathway that can be targetted to reduce or prevent excessive ASM mass in COPD.

Design and biological evaluation of imidazo[1,2-a]pyridines as novel and potent ASK1 inhibitors.[Pubmed:23147077]

Bioorg Med Chem Lett. 2012 Dec 15;22(24):7326-9.

Imidazo[1,2-a]pyridine derivatives were designed, synthesized, and evaluated as inhibitors of the apoptosis signal-regulating kinase 1 (ASK1). These were based on a benzothiazole derivative that was discovered from high-throughput screening of our compound library. As a result, we identified potent, selective, and orally bioavailable ASK1 inhibitors for wide range of therapeutic targets.

Description

TC ASK 10 (Compound 10) is a potent, selective and orally active apoptosis signal-regulating kinase 1 (ASK1) inhibitor with an IC50 of 14 nM. The inhibitory activities of TC ASK 10 towards other representative panel of kinases are less than 50%, except for ASK2 (IC50 of 0.51 μM).

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