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| 25mg |
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Purity: ≥98%
K-858 is a novel, potent and ATP-uncompetitive inhibitor of mitotic kinesin Eg5 that has potential antitumor activity. K858 is a strong replication inhibitor that, regardless of the tumor phenotype, causes apoptosis in breast tumor cells. Since survivin is overexpressed at the same time as K858, this anti-proliferative response of tumor cells to K858 may be restricted. As a result, tumor cells may become more susceptible to K858-induced apoptosis if survivin levels are reduced by using AKT inhibitors. K858 caused cells to enter mitotic arrest and form monopolar spindles by blocking centrosome separation and activating the spindle checkpoint. K858 triggers growth inhibition and mitotic arrest by activating the spindle checkpoint mediated by Mad2. K858 causes cancer cells to undergo mitosis, but not healthy cells. K858 inhibits cell growth, causes apoptosis, and induces mitotic arrest; microtubule polymerization is unaffected.
| Targets |
Eg5 (IC50 = 1.3 μM)
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| ln Vitro |
K858 Racemic has an IC50 of 1.3 μM and inhibits Eg5 in an ATP-uncompetitive manner. Even at 200 μM, neither the conventional kinesin heavy chain nor the mitotic kinesins CENP-E and MKLP1 have their ATPase activity inhibited by K858. By activating the spindle checkpoint mediated by Mad2, K858 causes mitotic arrest and growth inhibition. In cancer cells, K858 (5 μM) induces mitotic cell death, but not in healthy cells[1]. The MCF7, BT474, and SKBR3 cell lines are inhibited by K858 (1, 10, and 100 μM), and the MDA-MB231 cell line is only suppressed at 10 and 100 μM after a 24-hour treatment. K858 decreases survivin and the Bax/Bcl2 RNA ratio in the four cell lines. Furthermore, in MCF7 cells, wortmannin (phosphoinositide 3-kinase AKT) completely reverses the up-regulation of survivin[2].
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| ln Vivo |
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| Cell Assay |
The sulforhodamine B colorimetric assay is used to assess cytotoxicity. 1.5 × 104 cells are seeded onto 96-well plates, allowed to grow for 24 hours (h), and then exposed to varying K858 concentrations (1 μM, 10 μM, and 100 μM) for 24 and 48 hours. Following a one-hour fixation in 50% trichloroacetic acid at 4°C, the cells are stained with 0.4% sulforhodamine B in 1% acetic acid for thirty minutes at room temperature (RT). Washing four times with 1% acetic acid gets rid of extra dye. Using a microplate reader, protein-bound dye is dissolved in 10 mM TRIS pH 10 and optical density (OD) is measured at 510 nm[2].
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| Animal Protocol |
BALB/cAJcl-nu mice receive a single-cell inoculation of 5 × 106 A2780 cells. K858 is given orally at 150 and 50 mg/kg twice a day on days 0 through 4 and 7 through 11. The tolerability studies that are conducted beforehand dictate the doses and schedules. Oral administration of the vehicle (0.5% methylcellulose 400) is done twice a day on days 0 through 4 and 7 through 11. On day 0, 25 mg/kg of paclitaxel is injected intravenously. On day 0, 60 mg/kg of carboplatin is injected intravenously. The ratio of the mean experimental V/V0 value to the control group's value is known as the treated versus control (T/C) ratio. In this ratio, V represents the tumor volume on the evaluation day and V0 represents the tumor volume on the day of the drug's first administration. The nonparametric rank-sum test is used in statistical analysis[1].
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| References |
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| Additional Infomation |
N-(4-acetyl-5-methyl-5-phenyl-1,3,4-thiadiazol-2-yl)acetamide is a member of benzenes.
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| Molecular Formula |
C13H15N3O2S
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| Molecular Weight |
277.34
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| Exact Mass |
277.088
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| Elemental Analysis |
C, 56.30; H, 5.45; N, 15.15; O, 11.54; S, 11.56
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| CAS # |
72926-24-0
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| Related CAS # |
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| PubChem CID |
2930014
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.627
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| LogP |
1.05
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
19
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| Complexity |
418
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(NC1=NN(C(C)=O)C(C2=CC=CC=C2)(C)S1)=O
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| InChi Key |
JEFVYQYZCAVNTP-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
N-(4-acetyl-5-methyl-5-phenyl-1,3,4-thiadiazol-2-yl)acetamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.01 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (9.01 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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