| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg | |||
| Other Sizes |
| Targets |
Litronesib targets Eg5 (kinesin spindle protein, KSP), a mitotic kinesin essential for the formation of bipolar mitotic spindles during cell division. It acts as a selective, allosteric inhibitor of kinesin Eg5. By binding to an allosteric site on Eg5, litronesib inhibits the motor protein's ATPase activity, preventing the proper separation of centrosomes and leading to the formation of monopolar spindles. This disruption of mitosis results in cell cycle arrest and apoptosis, particularly in rapidly dividing cancer cells.
|
|---|---|
| ln Vitro |
In vitro studies have demonstrated that litronesib effectively inhibits Eg5 ATPase activity and disrupts mitotic spindle formation in cancer cell lines. The compound induces cell cycle arrest at the G2/M phase and triggers apoptosis in rapidly dividing cells. Litronesib racemate shows potent antiproliferative activity against various cancer cell lines, including those derived from solid tumors and hematologic malignancies. The compound's activity is attributed to its ability to bind the allosteric site of Eg5, causing conformational changes that inhibit the motor protein's function. Cell viability assays (MTT or CellTiter-Glo) are used to assess the compound's antiproliferative effects, with IC50 values typically in the low micromolar to nanomolar range depending on the cell line.
|
| ln Vivo |
In vivo studies have explored litronesib racemate as an anticancer agent in preclinical models. The compound has been evaluated in xenograft mouse models bearing human tumor cell lines, where it demonstrates dose-dependent inhibition of tumor growth. The in vivo efficacy is attributed to the compound's ability to inhibit Eg5, disrupt mitosis, and induce apoptosis in tumor cells. Tumor growth inhibition, regression, and survival benefits have been reported in various preclinical models. The compound has also been investigated in clinical studies for solid tumors and hematologic malignancies.
|
| Enzyme Assay |
The in vitro enzyme assay for litronesib involves measuring its inhibition of Eg5 ATPase activity. Purified Eg5 motor protein is incubated with varying concentrations of litronesib (typically 0.1 nM to 100 uM) in the presence of ATP and microtubules. The ATPase activity is measured using a coupled enzyme assay where ATP hydrolysis is linked to NADH oxidation, monitored spectrophotometrically at 340 nm. Alternatively, a malachite green phosphate detection assay can be used to quantify inorganic phosphate released from ATP hydrolysis. IC50 values are determined by fitting the data to a four-parameter logistic equation. The allosteric nature of inhibition is confirmed by assessing binding at multiple ATP concentrations.
|
| Cell Assay |
In vitro cellular assays for litronesib are conducted using cancer cell lines that are sensitive to Eg5 inhibition. Cells are seeded in 96-well or 6-well plates and treated with varying concentrations of litronesib racemate (typically 0.001-100 uM) for 24-72 hours. Cell viability is assessed using MTT, CellTiter-Glo, or crystal violet staining assays. Cell cycle analysis is performed by flow cytometry using propidium iodide staining to assess the accumulation of cells in G2/M phase. Apoptosis is evaluated using Annexin V-FITC/PI double staining or by measuring caspase-3/7 activity. Immunofluorescence staining for alpha-tubulin and pericentrin is used to visualize mitotic spindle morphology and confirm monopolar spindle formation.
|
| Animal Protocol |
In vivo animal studies for litronesib typically involve subcutaneous xenograft models in immunodeficient mice (e.g., nude or SCID mice). Human cancer cells (e.g., 5-10 × 10⁶ cells) are implanted subcutaneously into the flank of mice. When tumors reach a volume of approximately 100-200 mm3, mice are randomized to receive litronesib racemate or vehicle control. The compound is administered by various routes including oral gavage or intraperitoneal injection, typically at doses ranging from 1-50 mg/kg, on a schedule such as daily or every other day for 2-4 weeks. Tumor volumes are measured twice weekly with calipers, and body weights are monitored for toxicity. At study termination, tumors are excised for histological analysis and biomarker evaluation.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of litronesib racemate have been characterized in preclinical studies. The compound has a molecular weight of 511.70 and a molecular formula of C23H37N5O4S2. It is soluble in DMSO at concentrations up to 100 mg/mL (195.43 mM). The racemate form is used to evaluate the pharmacokinetic profiles of both enantiomers in early-stage research. The compound is typically administered orally or intravenously in animal studies, with plasma concentrations measured by LC-MS/MS. Standard pharmacokinetic parameters including Cmax, Tmax, half-life, AUC, and bioavailability are determined from concentration-time data. The compound should be stored at -20degC in dry, dark conditions.
|
| Toxicity/Toxicokinetics |
Toxicology data for litronesib racemate are derived from preclinical safety studies. As an Eg5 inhibitor that disrupts mitosis, the compound is expected to have effects on rapidly dividing tissues including bone marrow, gastrointestinal epithelium, and hair follicles. In animal studies, dose-limiting toxicities are typically associated with mitotic inhibition in proliferating tissues. The compound has been evaluated in clinical studies, and adverse events are consistent with those of other antimitotic agents. Standard toxicology parameters including hematology, clinical chemistry, and histopathology are monitored in animal studies. The compound is for research use only and not for human therapeutic use.
|
| References | |
| Additional Infomation |
Litronesib racemate (CAS 546111-97-1) is also known as LY2523355 Racemate and KF-89617 Racemate. The compound is a selective, allosteric inhibitor of kinesin Eg5 and has been explored as an anticancer agent in preclinical and clinical studies. The racemate contains both enantiomers of litronesib and is used in early-stage research. The compound's mechanism involves inhibition of Eg5, disruption of mitotic spindle formation, cell cycle arrest at G2/M, and induction of apoptosis. It is available for research purposes only with purity ≥95% and should be stored at -20degC.
|
| Molecular Formula |
C23H37N5O4S2
|
|---|---|
| Molecular Weight |
511.700982809067
|
| Exact Mass |
511.228
|
| CAS # |
546111-97-1
|
| Related CAS # |
Litronesib;910634-41-2
|
| PubChem CID |
11272219
|
| Appearance |
White to off-white solid powder
|
| Density |
1.2±0.1 g/cm3
|
| Index of Refraction |
1.587
|
| LogP |
2.56
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
34
|
| Complexity |
865
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
YVAFBXLHPINSIK-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H37N5O4S2/c1-8-24-14-15-34(31,32)25-16-23(17-12-10-9-11-13-17)28(19(30)22(5,6)7)27-20(33-23)26-18(29)21(2,3)4/h9-13,24-25H,8,14-16H2,1-7H3,(H,26,27,29)
|
| Chemical Name |
N-[4-(2,2-dimethylpropanoyl)-5-[[2-(ethylamino)ethylsulfonylamino]methyl]-5-phenyl-1,3,4-thiadiazol-2-yl]-2,2-dimethylpropanamide
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~195.43 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.89 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 (4.89 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.89 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9543 mL | 9.7714 mL | 19.5427 mL | |
| 5 mM | 0.3909 mL | 1.9543 mL | 3.9085 mL | |
| 10 mM | 0.1954 mL | 0.9771 mL | 1.9543 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
