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KPT-276

Catalog No.GC12142

inhibitor of nuclear export (SINE) and CRM1, orally bioavailable

Products are for research use only. Not for human use. We do not sell to patients.

KPT-276 Chemical Structure

Cas No.: 1421919-75-6

Size Price Stock Qty
10mM (in 1mL DMSO)
$46.00
In stock
10mg
$48.00
In stock
50mg
$142.00
In stock

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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

Twelve human myeloma cell lines

Preparation method

The solubility of this compound in DMSO is >19.85 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.

Reacting condition

24 h

Applications

In twelve HMCLs, treatment with KPT-276 (≤ 1 μM) for 72 h reduced cell viability with a median IC50 value of approximately 160 nM. KPT-276 treatment reduced c-Myc, CDC25A and BRD4 levels in both MM1.S and OCI-MY5. Treatment with KPT-276 for 24 h induced cell cycle arrest in MM1.S cells.

Animal experiment [1]:

Animal models

Athymic NCr-nu/nu mice bearing MM1.S cells, Vk*MYC mouse model

Dosage form

Oral gavage, 150 mg/kg, 3 days/week for 3 weeks;

Application

In a xenograft MM1.S MM model, the tumor volume significantly decreased after treatment with KPT-276 (12 days). KPT-276 reduced monoclonal spikes in the Vk*MYC transgenic MM mouse model, and inhibited tumor growth in a xenograft MM mouse model.

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.

References:

[1]. Schmidt J, Braggio E, Kortuem K M, et al. Genome-wide studies in multiple myeloma identify XPO1/CRM1 as a critical target validated using the selective nuclear export inhibitor KPT-276[J]. Leukemia, 2013, 27(12): 2357.

Background

KPT-276, analog of KPT-185, is a selective inhibitor of nuclear export (SINE) and CRM1 [1].

Chromosomemaintenance protein 1 (CRM1) is a nuclear export receptor involved in the active transport of transcription factors, cell-cycle regulators, tumor suppressors and RNA molecules. In cancer, CRM1 is overexpression and overactive transport [1].

KPT-276 is an orally bioavailable and selective CRM1 inhibitor that irreversibly binds to CRM1 and blocks CRM1-mediated nuclear export [1]. In human multiple myeloma (MM) cell lines (HMCLs), KPT-276 irreversibly and specifically inhibited the nuclear export of XPO1, which encoded CRM1 and significantly reduced the viability of HMCLs. In bone marrow cells isolated from MM patients, KPT-276 induced apoptosis. Also, KPT-276 downregulated the expression of c-MYC, CDC25A and BRD4, which caused G1/S phase arrest [2].

In a xenograft human acute myeloid leukemia (AML) murine model, KPT-276 significantly increased the survival of mice and reduced the amount of white blood cells. Also, KPT-276 significantly reduced spleen weight and FLT3 protein expression [1]. In a xenograft MM mouse model, KPT-276 inhibited tumor growth [2].

References:
[1].  Ranganathan P, Yu X, Na C, et al. Preclinical activity of a novel CRM1 inhibitor in acute myeloid leukemia. Blood, 2012, 120(9): 1765-1773.
[2].  Schmidt J, Braggio E, Kortuem KM, et al. Genome-wide studies in multiple myeloma identify XPO1/CRM1 as a critical target validated using the selective nuclear export inhibitor KPT-276. Leukemia, 2013, 27(12): 2357-2365.

Chemical Properties

Cas No. 1421919-75-6 SDF
Chemical Name (Z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-1-(3,3-difluoroazetidin-1-yl)prop-2-en-1-one
Canonical SMILES C1C(CN1C(=O)C=CN2C=NC(=N2)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)(F)F
Formula C16H10F8N4O M.Wt 426.26
Solubility ≥ 19.85mg/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

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 2.346 mL 11.7299 mL 23.4599 mL
5 mM 0.4692 mL 2.346 mL 4.692 mL
10 mM 0.2346 mL 1.173 mL 2.346 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.

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Average Rating: 5 ★★★★★ (Based on Reviews and 3 reference(s) in Google Scholar.)

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