[CAS NO. 72926-24-0] K858(Racemic)
PRODUCTS SPECIFICATIONS [72926-24-0]
DESCRIPTION [72926-24-0]
Overview
| MDL | MFCD00181155 |
|---|---|
| Molecular Weight | 277.34 |
| Molecular Formula | C13H15N3O2S |
| SMILES | CC(NC1=NN(C(C)=O)C(C2=CC=CC=C2)(C)S1)=O |
Summary
K858 Racemic is an ATP-uncompetitive inhibitor of kinesin Eg5 with an IC 50 of 1.3 μM.
IC50 & Target
|
Eg5 1.3 μM (IC 50 ) |
In Vitro
K858 Racemic is an ATP-uncompetitive inhibitor of Eg5 with an IC 50 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] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 100 mg/mL ( 360.57 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent 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 |
-
1.
-
2.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (9.01 mM); Clear solution
References
- [1] Nakai R, et al. K858, a novel inhibitor of mitotic kinesin Eg5 and antitumor agent, induces cell death in cancer cells. Cancer Res. 2009 May 1;69(9):3901-9.
- [2] De Iuliis F, et al. The kinesin Eg5 inhibitor K858 induces apoptosis but also survivin-related chemoresistance in breast cancer cells. Invest New Drugs. 2016 Aug;34(4):399-406.