1. Cell Cycle/DNA Damage
    Cytoskeleton
  2. Kinesin

K858 

Cat. No.: HY-19966 Purity: 99.76%
Handling Instructions

K858 is an ATP-uncompetitive inhibitor of Eg5 with an IC50 of 1.3 μM.

For research use only. We do not sell to patients.

K858 Chemical Structure

K858 Chemical Structure

CAS No. : 72926-24-0

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 92 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
5 mg USD 84 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
10 mg USD 144 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
50 mg USD 540 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
100 mg USD 780 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

K858 is an ATP-uncompetitive inhibitor of Eg5 with an IC50 of 1.3 μM.

IC50 & Target[1]

Eg5

1.3 μM (IC50)

In Vitro

K858 is an ATP-uncompetitive inhibitor of Eg5 with an IC50 of 1.3 μM. K858 does not inhibit the ATPase activity of the mitotic kinesins CENP-E and MKLP1, or the conventional kinesin heavy chain even at 200 μM. K858 induces mitotic arrest and growth inhibition via the activation of the Mad2-mediated spindle checkpoint. K858 (5 μM) induces mitotic cell death in cancer cells but not in normal cells[1]. K858 (1, 10, 100 μM) inhibits the MCF7, BT474 and SKBR3 cell lines, and only at 10 and 100 μM suppresses MDA-MB231 cell line after treatment for 24 h. K858 incereases Bax/Bcl2 RNA ratio and survivin in the four cell lines. Furthermore, the up-regulation of survivin is totally reversed by wortmannin (phosphoinositide 3-kinase AKT) in MCF7 cells[2].

In Vivo

K858 (50, 150 mg/kg, p.o.) shows antitumor activity in an A2780 ovarian cancer xenograft model, also inhibits tumor grwoth in a HCT116 colon cancer xenograft model via 100 mg/kg twice a day orally for 5 days. K858 (100 mg/kg, p.o., qd ×5) displays no neurotoxic side effects in mice[1].

References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 3.6057 mL 18.0284 mL 36.0568 mL
5 mM 0.7211 mL 3.6057 mL 7.2114 mL
10 mM 0.3606 mL 1.8028 mL 3.6057 mL
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[2]

K858 is solubilized in DMSO at 1 mM stock solution and utilized to final concentration of 10 μM.

To determine cytotoxicity, sulforhodamine B colorimetric assay is performed: 1.5 × 104 cells are plated on 96 well plates, grown for 24 h (h) and treated with different concentrations of K858 (1 μM, 10 μM, 100 μM) for 24 and 48 h. Cells are then fixed with 50 % trichloroacetic acid for 1 h at 4°C and stained for 30 min at room temperature (RT) with 0.4 % sulforhodamine B in 1 % acetic acid. Excess dye is removed by washing four times with 1 % acetic acid. Protein bound dye is dissolved in 10 mM TRIS pH 10, and optical density (OD) is determined at 510 nm using a microplate reader[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

K858 is formulated in 0.5% methylcellulose 400.

A2780 cells (5 × 106 cells) are inoculated s.c. into BALB/cAJcl-nu mice. K858 is administered orally twice daily on days 0 to 4, and 7 to 11 at 150 and 50 mg/kg. Doses and schedules are determined by the tolerability studies performed in advance. Vehicle (0.5% methylcellulose 400) is administered orally as a control twice daily on days 0 to 4, and 7 to 11. Paclitaxel is administered i.v. on day 0 at 25 mg/kg. Carboplatin is administered i.v. on day 0 at 60 mg/kg. Drug efficacy is expressed as the ratio of the mean experimental V/V0 value to that of the control group [treated versus control (T/C) ratio], where V is the tumor volume at the day of evaluation and V0 is the tumor volume at the day of the initial treatment with the drug. Statistical analysis is performed using the nonparametric rank-sum test[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

277.34

Formula

C₁₃H₁₅N₃O₂S

CAS No.

72926-24-0

SMILES

CC(NC1=NN(C(C)=O)C(C2=CC=CC=C2)(C)S1)=O

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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Product Name:
K858
Cat. No.:
HY-19966
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