Synonym
K-858; K 858; K858.
IUPAC/Chemical Name
N-(4-acetyl-5-methyl-5-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamide
InChi Key
JEFVYQYZCAVNTP-UHFFFAOYSA-N
InChi Code
InChI=1S/C13H15N3O2S/c1-9(17)14-12-15-16(10(2)18)13(3,19-12)11-7-5-4-6-8-11/h4-8H,1-3H3,(H,14,15,17)
SMILES Code
CC(NC1=NN(C(C)=O)C(C2=CC=CC=C2)(C)S1)=O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
K858 Racemic is an ATP-uncompetitive inhibitor of kinesin Eg5 with an IC50 of 1.3 μM.
In vitro activity:
K858 inhibited cell replication by rendering cells incapable of developing normal bipolar mitotic spindles. At the same time, K858 blocked the cell cycle in the G2 phase and induced the accumulation of cytoplasmic cyclin B and, eventually, apoptosis. Additionally, K858 inhibited cell migration and attenuated the malignant phenotype.
Reference: Invest New Drugs. 2022 Jun;40(3):556-564. https://pubmed.ncbi.nlm.nih.gov/35312942/
In vivo activity:
K858 exhibited potent antitumor activity in xenograft models of cancer, and induced the accumulation of mitotic cells with monopolar spindles in tumor tissues. Importantly, K858, unlike antimicrotubule agents, had no effect on microtubule polymerization in cell-free and cell-based assays, and was not neurotoxic in a motor coordination test in mice. Taken together, the Eg5 inhibitor K858 represents an important compound for further investigation as a novel anticancer therapeutic.
Reference: Cancer Res. 2009 May 1;69(9):3901-9. https://pubmed.ncbi.nlm.nih.gov/19351824/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
25.0 |
90.14 |
| DMSO |
61.7 |
222.35 |
| DMSO:PBS (pH 7.2) (1:4) |
0.2 |
0.72 |
| Ethanol |
4.0 |
14.42 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
277.34
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Nicolai A, Taurone S, Carradori S, Artico M, Greco A, Costi R, Scarpa S. The kinesin Eg5 inhibitor K858 exerts antiproliferative and proapoptotic effects and attenuates the invasive potential of head and neck squamous carcinoma cells. Invest New Drugs. 2022 Jun;40(3):556-564. doi: 10.1007/s10637-022-01238-2. Epub 2022 Mar 21. PMID: 35312942; PMCID: PMC9098576.
2. Marconi GD, Carradori S, Ricci A, Guglielmi P, Cataldi A, Zara S. Kinesin Eg5 Targeting Inhibitors as a New Strategy for Gastric Adenocarcinoma Treatment. Molecules. 2019 Oct 31;24(21):3948. doi: 10.3390/molecules24213948. PMID: 31683688; PMCID: PMC6864856.
3. Nakai R, Iida S, Takahashi T, Tsujita T, Okamoto S, Takada C, Akasaka K, Ichikawa S, Ishida H, Kusaka H, Akinaga S, Murakata C, Honda S, Nitta M, Saya H, Yamashita Y. 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. doi: 10.1158/0008-5472.CAN-08-4373. Epub 2009 Apr 7. PMID: 19351824.
In vitro protocol:
1. Nicolai A, Taurone S, Carradori S, Artico M, Greco A, Costi R, Scarpa S. The kinesin Eg5 inhibitor K858 exerts antiproliferative and proapoptotic effects and attenuates the invasive potential of head and neck squamous carcinoma cells. Invest New Drugs. 2022 Jun;40(3):556-564. doi: 10.1007/s10637-022-01238-2. Epub 2022 Mar 21. PMID: 35312942; PMCID: PMC9098576.
2. Marconi GD, Carradori S, Ricci A, Guglielmi P, Cataldi A, Zara S. Kinesin Eg5 Targeting Inhibitors as a New Strategy for Gastric Adenocarcinoma Treatment. Molecules. 2019 Oct 31;24(21):3948. doi: 10.3390/molecules24213948. PMID: 31683688; PMCID: PMC6864856.
In vivo protocol:
1. Nakai R, Iida S, Takahashi T, Tsujita T, Okamoto S, Takada C, Akasaka K, Ichikawa S, Ishida H, Kusaka H, Akinaga S, Murakata C, Honda S, Nitta M, Saya H, Yamashita Y. 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. doi: 10.1158/0008-5472.CAN-08-4373. Epub 2009 Apr 7. PMID: 19351824.
1: Indorato RL, DeBonis S, Kozielski F, Garcia-Saez I, Skoufias DA.
STLC-resistant cell lines as tools to classify chemically divergent Eg5 targeting
agents according to their mode of action and target specificity. Biochem
Pharmacol. 2013 Nov 15;86(10):1441-51. doi: 10.1016/j.bcp.2013.09.003. Epub 2013
Sep 13. PubMed PMID: 24041742.
2: Nakai R, Iida S, Takahashi T, Tsujita T, Okamoto S, Takada C, Akasaka K,
Ichikawa S, Ishida H, Kusaka H, Akinaga S, Murakata C, Honda S, Nitta M, Saya H,
Yamashita Y. 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. doi:
10.1158/0008-5472.CAN-08-4373. Epub 2009 Apr 7. PubMed PMID: 19351824.
