CAS 72926-24-0|K 858

Introduction：Basic information about CAS 72926-24-0|K 858, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. K 858 BiologicalActivity
3. Chemical & Physical Properties
4. Safety Information
5. Customs
6. Synonyms

Common Name	K 858
CAS Number	72926-24-0	Molecular Weight	277.342
Density	1.3±0.1 g/cm3	Boiling Point	/
Molecular Formula	C₁₃H₁₅N₃O₂S	Melting Point	/
MSDS	ChineseUSA	Flash Point	/
Symbol	GHS07	Signal Word	Warning

Names

Name	N-(4-Acetyl-5-methyl-5-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamide
Synonym	More Synonyms

K 858 BiologicalActivity

Description	K858 Racemic is an ATP-uncompetitive inhibitor of Eg5 with an IC50 of 1.3 μM.
Related Catalog	Signaling Pathways >>Cell Cycle/DNA Damage >>KinesinSignaling Pathways >>Cytoskeleton >>KinesinResearch Areas >>Cancer
Target	Eg5:1.3 μM (IC50)
In Vitro	K858 Racemic 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].
Cell Assay	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].
Animal Admin	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].
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.

Chemical & Physical Properties

Density	1.3±0.1 g/cm3
Molecular Formula	C₁₃H₁₅N₃O₂S
Molecular Weight	277.342
Exact Mass	277.088501
PSA	90.56000
LogP	1.05
Index of Refraction	1.627
InChIKey	JEFVYQYZCAVNTP-UHFFFAOYSA-N
SMILES	CC(=O)NC1=NN(C(C)=O)C(C)(c2ccccc2)S1

Safety Information

Symbol	GHS07
Signal Word	Warning
Hazard Statements	H302
RIDADR	NONH for all modes of transport
HS Code	2934999090

Customs

HS Code	2934999090
Summary	2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Synonyms

UNII:ZA4OIM722G

2,4,6-Cycloheptatrien-1-one,3-acetyl-5,7-dibromo-2-hydroxy

3-acetyl-5-acetylamino-2-methyl-2-phenyl-2,3-dihydro-[1,3,4]thiadiazole

3-acetyl-5,7-dibromotropolone

(R)-3,4-DCPG

Acetamide, N-(4-acetyl-4,5-dihydro-5-methyl-5-phenyl-1,3,4-thiadiazol-2-yl)-

N-(4-Acetyl-5-methyl-5-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamide

K 858

K858

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