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ACHP

Catalog No.GC17416

IκB kinase inhibitor

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ACHP Chemical Structure

Cas No.: 406208-42-2

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10mg
$397.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

Cell lines

U266 and NCUMM-2 myeloma cell lines

Preparation method

The solubility of this compound in DMSO is > 10 mM. 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.

Reacting condition

0-50 μM; 8 h

Applications

In U266 and NCUMM-2 myeloma cell lines, ACHP (>10 μmol/L) inhibited the DNA binding activity of NF-κB after only 4 hours. ACHP also efficiently inhibited the phosphorylation of IκBαand p65 at 1 μmol/L after 20 minutes treatment. ACHP (10 μmol/L, 24h) also inhibited cell cycle progression and induced apoptosis. In NCUMM-2 cells, ACHP (10 μmol/L) efficiently induced apoptosis (15.8%) and a higher concentration of ACHP (50 μmol/L) induced apoptosis in 43.7% of the cells.

References:

[1] Sanda T, Iida S, Ogura H, Asamitsu K, Murata T, Bacon KB, Ueda R, Okamoto T. Growth inhibition of multiple myeloma cells by a novel IkappaB kinase inhibitor. Clin Cancer Res. 2005 Mar 1;11(5):1974-82.

Background

IC50: 8.5 and 250 nM for IKKβ and IKKα, respectively

ACHP is an IκB kinase inhibitor. Nuclear factor-KB (NF-KB) involved in cell survival and proliferation of multiple myeloma has been well established.

In vitro: ACHP is selective for IKKα and IKKβ over IKK3, Syk and MAPKKK4 (IC50 > 20 μM), DNA binding activity of NF-κB is inhibited. ACHP is an effective blockade NF-κB pathway in multiple myeloma cell lines, and induces cell growth arrest and apoptosis. It was observed that NF-KB is constitutively activated in all human myeloma cell lines, thus confirming the previous studies. In addition, It was found the phosphorylation of p65 subunit of NF-KB besides the phosphorylation of IKBA and the activation of NF-KB DNA binding and that various target genes of NF-KB including bcl-xL, XIAP, c-IAP1, cyclin D1, and IL-6 are up-regulated. 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl nicotinenitrile (ACHP) is a novel IKB kinase inhibitor. Treatment of myeloma cells with ACHP showed the cell growth was efficiently inhibited (IC50 values ranging from 18 to 35 Mmol/L) concomitantly with inhibition of the phosphorylation of IKBA/p65 and NF-KB DNA-binding, down-regulation of the NF-KB target genes, and then induction of apoptosis. In addition, the treatment of ACHP potentiated the cytotoxic effects of vincristine and melphalan (L-phenylalanine mustard), conventional antimyeloma drugs. These findings suggest that by blocking the antiapoptotic nature of myeloma cells endowed by the constitutive activation of NF-KB, IKB kinase inhibitors such as ACHP can sensitize myeloma cells to the cytotoxic effects of chemotherapeutic agents.

In vivo: So far, no study in vivo has been conducted.

Clinical trial: Clinical study has been conducted.

Reference:
[1] Sanda T, Iida S, Ogura H, Asamitsu K, Murata T, Bacon KB, Ueda R, Okamoto T.  Growth inhibition of multiple myeloma cells by a novel IkappaB kinase inhibitor. Clin Cancer Res. 2005 Mar 1;11(5):1974-82.

Chemical Properties

Cas No. 406208-42-2 SDF
Chemical Name (E)-2-amino-6-(2-(cyclopropylmethoxy)-6-oxocyclohexa-2,4-dien-1-ylidene)-4-(piperidin-4-yl)-1,6-dihydropyridine-3-carbonitrile
Canonical SMILES O=C1/C(C(OCC2CC2)=CC=C1)=C3NC(N)=C(C#N)C(C4CCNCC4)=C/3
Formula C21H24N4O2 M.Wt 364.44
Solubility <7.29mg/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.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.7439 mL 13.7197 mL 27.4394 mL
5 mM 0.5488 mL 2.7439 mL 5.4879 mL
10 mM 0.2744 mL 1.372 mL 2.7439 mL
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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.

Reviews

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Average Rating: 5 ★★★★★ (Based on Reviews and 36 reference(s) in Google Scholar.)

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